Meg Acet in Anorexia

Megestrol acetate for treatment of anorexia-cachexia

syndrome (Review)

Berenstein EG, Ortiz Z

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library2008, Issue 3

http://www.thecochranelibrary.com

1Megestrol acetate for treatment of anorexia-cachexia syndrome (Review)

Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

http://www.thecochranelibrary.com

T A B L E O F C O N T E N T S

1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW . . . . . . . . . . . . . . . . . .

3SEARCH METHODS FOR IDENTIFICATION OF STUDIES . . . . . . . . . . . . . . . . . . .

4METHODS OF THE REVIEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4DESCRIPTION OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6METHODOLOGICAL QUALITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

8DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

9AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

9POTENTIAL CONFLICT OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . .

9ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

9SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

10REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12Characteristics of included studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

25Characteristics of excluded studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

25ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

25Table 01. Patient condition and numbers recruited to each trial . . . . . . . . . . . . . . . . . . .

27Table 02. EMBASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

28Table 03. Cochrane Pain, Palliative and Supportive Care Group Trials register . . . . . . . . . . . . . .

28ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

28Comparison 01. Megestrol acetate vs placebo (ITT) . . . . . . . . . . . . . . . . . . . . . . .

28Comparison 02. Megestrol acetate vs other drugs (ITT) . . . . . . . . . . . . . . . . . . . . .

29Comparison 03. Sensitivity analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . .

29INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

29COVER SHEET . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

30GRAPHS AND OTHER TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

31Analysis 01.01. Comparison 01 Megestrol acetate vs placebo (ITT), Outcome 01 Appetite improvement . . . .

32Analysis 01.02. Comparison 01 Megestrol acetate vs placebo (ITT), Outcome 02 Weight gain . . . . . . . .

33Analysis 01.03. Comparison 01 Megestrol acetate vs placebo (ITT), Outcome 03 Weight gain . . . . . . . .

34Analysis 01.04. Comparison 01 Megestrol acetate vs placebo (ITT), Outcome 04 Quality of life . . . . . . .

35Analysis 01.05. Comparison 01 Megestrol acetate vs placebo (ITT), Outcome 05 Side effects . . . . . . . .

36Analysis 02.01. Comparison 02 Megestrol acetate vs other drugs (ITT), Outcome 01 Appetite improvement . . .

37Analysis 02.02. Comparison 02 Megestrol acetate vs other drugs (ITT), Outcome 02 Weight gain . . . . . . .

38Analysis 02.03. Comparison 02 Megestrol acetate vs other drugs (ITT), Outcome 03 Weight gain . . . . . . .

39Analysis 02.04. Comparison 02 Megestrol acetate vs other drugs (ITT), Outcome 04 Quality of life . . . . . .

40Analysis 03.01. Comparison 03 Sensitivity analysis, Outcome 01 Appetite improvement, treatment duration . . .

40Analysis 03.02. Comparison 03 Sensitivity analysis, Outcome 02 Weight gain, treatment duration . . . . . . .

41Analysis 03.03. Comparison 03 Sensitivity analysis, Outcome 03 Weight gain, treatment duration . . . . . . .

41Analysis 03.04. Comparison 03 Sensitivity analysis, Outcome 04 Appetite improvement, study quality . . . . .

42Analysis 03.05. Comparison 03 Sensitivity analysis, Outcome 05 Weight gain, study quality . . . . . . . . .

43Analysis 03.06. Comparison 03 Sensitivity analysis, Outcome 06 Weight gain, study quality . . . . . . . . .

iMegestrol acetate for treatment of anorexia-cachexia syndrome (Review)


Megestrol acetate for treatment of anorexia-cachexiasyndrome (Review)

Berenstein EG, Ortiz Z

This record should be cited as:

Berenstein EG, Ortiz Z. Megestrol acetate for treatment of anorexia-cachexia syndrome. Cochrane Database of Systematic Reviews 2005,

Issue 2. Art. No.: CD004310. DOI: 10.1002/14651858.CD004310.pub2.

This version first published online: 20 April 2005 in Issue 2, 2005.

Date of most recent substantive amendment: 23 January 2005

A B S T R A C T

Background

This is an updated version of a previously published review in The Cochrane Library (Issue 2, 2005) on ’Megestrol acetate for the

treatment of anorexia-cachexia syndrome’.

Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993 MA was

approved by the USA’s Federal Drug Administration for the treatment of anorexia, cachexia, or unexplained weight loss in patients

with AIDS. The mechanism by which MA increases appetite is unknown, and its effectiveness for anorexia and cachexia in neoplastic

and AIDS patients is under investigation.

Objectives

To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and

other underlying pathologies.

Search strategy

Studies were sought through an extensive search of the electronic databases, journals, reference lists, contact with investigators and

other search strategies outlined in the methods. The most recent search for this update was carried out in June 2006.

Selection criteria

Studies were included in the review if they assessed megestrol acetate compared to placebo or other drug treatments in randomized

controlled trials of patients with a clinical diagnosis of anorexia-cachexia related to cancer, AIDS or another underlying pathology.

Data collection and analysis

Data extraction was conducted by two independent review authors, and methodological quality evaluated. Quantitative analyses were

performed using appetite and quality of life as a dichotomous variable, and weight gain was analysed as continuous and dichotomous

variables. Studies with more than 50% of patients lost to follow-up were excluded from the analysis.

Main results

Thirty trials were included in the original review, four new trials were identified for this update, but only two met the inclusion criteria

(4123 + 703 patients). Twenty-two trials compared MA at different doses with placebo; five compared different doses of MA versus

other drugs; two compared MA with other drugs and placebo; and five compared different doses of MA. For all patient conditions, meta-

analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer

patients. Analysing quality of life, clinical and statistical heterogeneity was found and discussed. There was insufficient information to

define the optimal dose of MA.

Authors’ conclusions

This review demonstrates that MA improves appetite and weight gain in patients with cancer. No overall conclusion about Quality

of Life (QoL) could be drawn due to heterogeneity. The small number of patients, methodological shortcomings and poor reporting

have not allowed us to recommend megestrol acetate in AIDS patients or with other underlying pathologies. Since the last version of



this review, none of the new relevant studies have provided additional information on this treatment, in contrast to other therapeutic

approaches that should be considered.

P L A I N L A N G U A G E S U M M A R Y

Megestrol acetate improves appetite and weight gain in patients with anorexia cachexia syndrome related to cancer.

Megestrol acetate’s mechanism of action is unknown. There are concerns regarding the possible recommendations for this drug;

particularly in the improvement of quality of life in health care and in cancer patients. Quality of life is the cornerstone for delivery of

good palliative medicine. The review found that megestrol acetate significantly increased appetite and weight gain in cancer patients

but there was not enough evidence to reach a conclusion about the effect on quality of life and the optimal dose. There was too little

information on AIDS patients or those patients with other underlying pathologies. A low incidence of adverse effects was found.

B A C K G R O U N D

This review is an update of a previously published review in TheCochrane Library (Issue 2, 2005) on megestrol acetate for anorexia

cachexia syndrome. Anorexia cachexia syndrome is a common

clinical problem that substantially impacts upon the quality of

life and survival of affected patients. It is characterized by loss of

appetite, weight loss and tissue wasting, accompanied by a decrease

in muscle mass and adipose tissue, impoverishing the quality of

life, and often preceding the patient’s death (Nelson 1994; Splinter

1992).

More than two-thirds of patients dying with advanced cancer suf-

fer from anorexia cachexia syndrome (Argilés 2001). Anorexia

cachexia syndrome is also described in other pathologies such as

Acquired Immune Deficiency Syndrome (AIDS); anorexia ner-

vosa; in degenerative illnesses of the central nervous system; and

in terminally ill patients (Von Roenn 1996). Incidence is variable

and difficult to determine but in general the syndrome may occur

in 15% to 40% of patients with cancer, and in more than 80% of

patients with advanced illness (Bruera 1992).

Cachexia in cancer patients is thought to occur as a result of

metabolic changes brought about by substances secreted by the tu-

mour and the host (Alexander 1993). Substances have been iden-

tified that cause severe anorexia and weight loss. Tumour necrosis

factor, synthesized by the host’s macrophages (important cells in

the immune system), and inflammatory cytokines (including in-

terleukin 1 (I1) and 6 (I6)) are considered responsible for some of

the clinical manifestations (Mantovani 1998).

Early intervention and attention to nutritional status are essential

in patients with anorexia cachexia syndrome. Pharmacological in-

terventions for neoplastic cachexia include drugs that stimulate the

appetite (megestrol acetate and dronabinol); cytokine inhibitors

(such as cyproheptadine, thalidomide, pentoxifylline and an eicos-

apentaenoic acid (EPA)); and anabolic agents such as nandrolone

decanoate, oxandrolone and corticosteroids (Balog 1998). EPA

seems to suppress well-characterized mediators of cancer associ-

ated wasting, including interleukin-6, an inflammatory cytokine.

It also acts over the proteolysis-inducing factor, another well-de-

scribed mediator (Barber 1999; Wigmore 1997).

Megestrol acetate is a synthetic progestogen agent. The biological

mechanism of the anti-tumoral activity of megestrol acetate is

not well understood but it probably acts on hormone-dependent

tumoral cells. Inhibitory effects on growth in the cellular cycle

are not phase-specific, but their activity seems to be maximized in

phase G1 of cellular division (Tchekmedyian 1986).

Megestrol acetate was first synthesized in England in 1963. De-

veloped as an oral contraceptive, the agent was first tested in the

treatment of breast cancer in 1967 and later on, for the treat-

ment of endometrial cancer. Megestrol acetate is currently used

to improve appetite and to increase weight in cancer-associated

anorexia. From September 1993 megestrol acetate was approved

by the Federal Drug Administration (FDA) in the USA for the

treatment of anorexia, cachexia, or unexplained weight loss in pa-

tients with AIDS. In addition, there are recent reports of the drug

being used to improve the quality of life of elderly patients with

cachexia. A possible role in anorexia nervosa has also been pro-

posed (Yeh 2000).

Megestrol acetate is commonly available as a tablet of 80 mg or

liquid form (40 mg of micronized megestrol acetate per mL). A

great variability in doses is observed in the scientific literature,

ranging from 100 mg to 1600 mg per day (Tchekmedyian 1992;

Von Roenn 1994). The liquid form is usually dosed at 20 ml per

day and the oral one is four tablets per day. The recommended

duration of treatment is six weeks or more. Megestrol acetate is

considered a relatively non toxic drug with a low incidence of

adverse effects such as fluid retention, venous thrombosis, diar-

rhea, rash, impotence, pruritus, increased blood sugar level, and

headache (Loprinzi 1990a; Vadell 1998; Von Roenn 1994).

Although the mechanism by which megestrol acetate increases ap-

petite is unknown, most hypotheses point to action on cytokines,



which inhibit the action of tumour necrosis factor on fatty tis-

sue and its products. Currently, interest is focused especially on

its effectiveness in the treatment of anorexia and cachexia in neo-

plastic and AIDS patients. Studies at the Mayo Clinic and The

North Central Cancer Treatment Group Study have reported and

reviewed multiple placebo-controlled, randomized, double blind,

clinical trials of megestrol acetate and other drugs for the improve-

ment of anorexia cachexia syndrome in all types of cancer (Jatoi

2004; Loprinzi 1990a).

O B J E C T I V E S

1) To evaluate the efficacy, effectiveness and safety of megestrol

acetate in palliating anorexia-cachexia syndrome in sub-groups of

patients with cancer, AIDS, and other underlying pathologies.

2) To determine the optimal dose regimen for megestrol acetate

in palliating the anorexia-cachexia syndrome.

C R I T E R I A F O R C O N S I D E R I N G

S T U D I E S F O R T H I S R E V I E W

Types of studies

Randomized controlled trials (RCTs) which may be double blind,

single blind or unblinded. Cross-over studies were included if they

reported the results of the first phase of the study. Both inpatient

and outpatient study settings were included.

Types of participants

Trials of patients with a clinical diagnosis of anorexia-cachexia re-

lated to cancer, AIDS or another underlying pathology (indepen-

dent of gender, age or race) were included.

Types of intervention

The review focuses on the following treatment comparisons:

a) Megestrol acetate at any dose versus placebo;

b) Megestrol acetate at any dose versus other active drug treat-

ments (stimulants of appetite such as dronabinol; cytokine in-

hibitors such as cyproheptadine, EPA and anabolic agents such as

nandrolone decanoate and corticosteroids);

c) Megestrol acetate at different doses.

Types of outcome measures

The following outcome measures were assessed:

• appetite increase, expressed as a dichotomous variable (number

of patients who experience appetite increase) or a continuous

variable (calorific intake expressed as calories/day);

• weight gain, measured as a dichotomous variable (number of

patients who gain weight) and as a continuous variable in kg/day

at the end of the treatment compared with the baseline;

• measurements of the mid-arm circumference and triceps skin

fold thickness by anthropometry, as a percentage of the differ-

ences in the total body muscle and fat mass;

• improvement in quality of life (QoL), by means of a validated

instrument, or with scales of functional scores (e.g., Index of

Karnofsky and performance status) that measure the well-be-

ing status of the patient. The QoL measures will depend on

the instrument used, e.g., patient assessments using a Likert-

type scale based on patients’ statements and self-report ques-

tionnaires; or the use of the Spitzer QL-Index of quality of life,

completed by the clinician.

Study withdrawals and dropouts were analyzed as:

• total number of dropouts and withdrawals,

• number of withdrawals due to lack of effectiveness of treatment,

• number of withdrawals due to adverse effects.

Adverse effects: these were analyzed as the number of patients who

suffer an event described as a side effect by the authors of each

study.

S E A R C H M E T H O D S F O R

I D E N T I F I C A T I O N O F S T U D I E S

See: Cochrane Pain, Palliative and Supportive Care Group

methods used in reviews.

The following electronic databases were searched to identify

relevant studies:

MEDLINE from 1966 to October 2002, subsequent search June

2006 (see below);

EMBASE from 1986 to 2002, subsequent search, week 28, 2006

(see additional Table 02);

The Cochrane Central Register of Controlled Trials

(CENTRAL), The Cochrane Library Issue 1, 2002, subsequent

search Issue 2, 2006.

The Cochrane Pain, Palliative and Supportive Care Group Trials

Register (June 2006) (see additional Table 03)

For the identification of studies included or considered for this

review, detailed search strategies were developed for each database

searched.

The general strategy for identifying RCTs in MEDLINE was

combined with the following specific strategy designed to retrieve

trials of megestrol acetate for cachexia.

The Medline search strategy is as follows, the details of the other

searches are included in the additional tables:

• (Acquired Immunodeficiency Syndrome“[All Fields] OR

(acquired immunodeficiency syndrome”[MeSH Terms] OR

AIDS [Text Word]))



• ((neoplasms“[MeSH Terms] OR Neoplasm [Text Word]) OR

cancer [Text Word]))

• ((end of life”[All Fields] OR (terminally ill“ [MeSH Terms]

OR Terminally ill [Text Word])) OR (terminal care”[MeSH

Terms] OR Terminal care[Text Word]))

• (cachexia“[MeSH Terms] OR cachexia [Text Word])

• (megestrol acetate” [MeSH Terms] OR megestrol acetate [Text

Word])

Lists of references of the included studies were checked to

identify further trials.

Studies were not excluded on the basis of language or publication

status (published, unpublished, in press, and in progress).

Additional data from published trials were sought by contacting

authors.

M E T H O D S O F T H E R E V I E W

Study selection

The results of the search strategy were independently screened

by two review authors (EGB, ZO) and assessed for inclusion in

the previous and updated review. Disagreement was resolved by

discussion. Reasons for excluding trials were reported.

Data extraction

Data on patients, methods, interventions, outcomes and results

were extracted by two review authors using a data extraction form

(EGB, ZO) in the previous and updated review. Differences were

resolved by consensus, and when necessary, in consultation with

a third review author.

Quality of studies

The methodological quality of the studies was evaluated using a

validated scale called the Oxford Quality Scale (Jadad 1996). This

scale includes an evaluation of the randomisation, blinding and

patient attrition. The scale produces a composite score ranging

from one (low quality) to five (high quality). The three item scale

is applied as follows:

• is the study randomised ? If ’yes’ , then one point If described,

is the randomisation appropriate? If ’yes’ add one point, if not

deduct one;

• is the study double blind ? If ’yes’, then one point. Is the double

blind method appropriate ? If ’yes’ add one point, if not deduct

one;

• are withdrawals and dropouts described? (i.e., the number and

reason for drop-outs for each of the treatment groups). If ’yes’,

add one point.

Allocation concealment was also evaluated as a parameter of quality

of the design of the studies, and is reported in the ’Characteristics

of included studies’ table.

Data analysis

Studies with more than 50% of patients lost to follow-up were not

included in the analysis. We only analyzed crossover studies that

included results from the first treatment period in order to avoid

carry-over effects.

For dichotomous variables, treatment effects were computed

as relative risk (RR) with 95% confidence intervals (CI).

For continuous variables measured weight gain differences in

means and their 95% CI were calculated (weighted mean

difference - (WMD)) and for quality of life (including different

scales), differences in means and their 95% CI were calculated

(standardised mean difference - (SMD)). Only validated scales

with a normal distribution were included for the analysis. Validity

of the scale was determined by the psychometric properties of the

instrument described in the trial by the review authors.

A random effect model was used in the analysis. Statistical

heterogeneity between studies was analysed with a Chi-square

test, using P < 0.1 as a cut-off value to represent the presence

of significant heterogeneity. When a high level of heterogeneity

was detected, attempts were made to identify the sources of the

heterogeneity, and subsequent meta-analysis were performed using

a random effect model.

Subgroup analysis

Analysis of subgroups was undertaken according to the underlying

pathology of the patients. Three subgroups of studies were defined:

• patients with AIDS;

• patients with cancer;

• patients with other underlying disease.

Sensitivity analysis

In order to explore the impact of specific factors on the meta-

analysis results, sensitivity analyses was undertaken with:

• studies of high methodological quality (defined as studies with

appropriate concealment of allocation, appropriate blinding,

and analysis by intention-to-treat (ITT));

• studies where patients received more than six weeks of

treatment.

The statistical analyses were carried out using the statistical

package, RevMan Analyses 1.0.2, in RevMan 4.2.10.

D E S C R I P T I O N O F S T U D I E S

Searching electronic databases identified:

• 99 reports in MEDLINE (from 1966 to October 2002, the

subsequent search identified 24 reports in MEDLINE (from

2002 to July 2006);



• 164 reports in EMBASE (from 1986 to 2002), the subsequent

search identified 24 in EMBASE (from 2002 to week 28, 2006);

and

• 71 in The Cochrane Central Register of Controlled Trials (Cen-

tral), (Issue 2, 2006), the subsequent search identified 59 re-

ports (in Issue 1, 2002).

Three abstracts retrieved from handsearching in CCRT (Central)

were identified in this updated review. We attempted to contact

the authors of these abstracts for further trials data but with no

success.

Excluded studies

In this 2006 update we excluded one additional study (Yeh 2004)

and one unpublished study (Macbeth 1994) taking the total of

excluded studies to three.

Included studies

Further independent assessment by two review authors led to the

selection of two new articles: one from Jatoi 2004 and the other

from Ulutin 2002. Three abstracts were included (Gambardella

1998; Pardo 2003; Zeca 1995), but two had only a small amount

of data, Gambardella 1998 had no data at all although it met the

inclusion criteria, however, as there was no data available at present

it was excluded from the analyses for now and should data become

available at a later date, it will be included in a future update.

Many of these citations were replicated across the three databases,

and five studies that appeared to meet the inclusion criteria were

subsequently found to be follow-up reports or duplicate publica-

tions (see ’Characteristics of excluded studies’ table).

A total of 34 reports (describing 35 trials) fully met the inclusion

criteria for this update and provided data for analysis.

The designs of the 34 trials were as follows:

Megestrol acetate at different doses compared with placebo

Twenty-two trials compared megestrol acetate at different doses

with placebo (Beller 1997; Bruera 1990; Bruera 1998; De Conno

1998; Erkurt 2000; Eubanks 2002; Feliu 1992; Fietkau 1996;

Loprinzi 1990b; Marchand 2000; McMillan 1994; McQuellon

2002; Oster 1994; Rowland 1996; Schmoll 1992; Tchekmedyian

1992; Vadell 1998; Von Roenn 1994; Weisberg 2002; Westman

1999; Yeh 2000; Zeca 1995).

Megestrol acetate at different doses compared with other treat-

ment drugs

Five trials compared different doses of megestrol acetate with other

drug treatments. Megestrol acetate was compared with dronabi-

nol in two studies (Jatoi 2002; Timpone 1997); dexamethasone

and fluoximesterone in one study (Loprinzi 1999); nandrolone

decanoate in one study (Batterham 2001) and eicosapentaenoic

acid (EPA) in one study (Jatoi 2004).

Megestrol acetate at different doses compared with other treat-

ment drugs and placebo

Two studies compared megestrol acetate with other drugs and

placebo (Lai 1994 (prednisolone); Chen 1997 (cisapride)).

Megestrol acetate at different doses

Five trials (compared different doses of megestrol acetate (Gebbia

1996; Heckmayr 1992; Loprinzi 1994; Pardo 2003; Ulutin 2002).

The included studies were categorized according to the health care

problem of the patient - see Table 01 for a summary.

Patient characteristics

A total of 4826 patients recruited were included in this update.

The mean age of patients included in the treatment and control

groups across all studies was 56 years. The proportion of males

to females in the treatment groups was 1343/562, compared to

2038/833 in the control groups.

Patients with any cancer

Twenty-six trials (total number of patients 4148) (Beller 1997;

Bruera 1990; Bruera 1998; Chen 1997; De Conno 1998; Erkurt

2000; Feliu 1992; Fietkau 1996; Gebbia 1996; Heckmayr 1992;

Jatoi 2002; Jatoi 2004; Lai 1994; Loprinzi 1990b; Loprinzi 1994;

Loprinzi 1999; McQuellon 2002; McMillan 1994;Pardo 2003;

Rowland 1996; Schmoll 1992; Tchekmedyian 1992; Vadell 1998;

Westman 1999; Ulutin 2002; Zeca 1995) assessed the effective-

ness of megestrol acetate for anorexia-cachexia syndrome in cancer

patients where the primary site was:

• lung cancer (1792 patients, 43%);

• gastrointestinal and pancreatic cancer (1045 patients, 25%);

• head and neck cancer (347 patients, 8%);

• gynecological cancer (74 patients, 2%);

• non-specified sites (890 patients, 21%).

Patients with AIDS

Four trials (total number of patients, 435) assessed the effectiveness

of megestrol acetate for anorexia-cachexia syndrome in AIDS pa-

tients (Batterham 2001; Oster 1994; Timpone 1997; Von Roenn

1994)

Patients with other underlying conditions

Four trials (total number of patients, 243) assessed the effectiveness

of megestrol acetate for anorexia-cachexia syndrome in patients

with the following conditions:

• chronic obstructive pulmonary disease (COPD): one trial

(Weisberg 2002) of 145 patients;

• cystic fibrosis: two trials (Marchand 2000 of 12 patients and

Eubanks 2002 of 17 patients);

• elderly: one trial (Yeh 2000) of 69 patients.

Dose

Across the studies, the dose of megestrol acetate ranged from 100

mg per day to 1600 mg per day in at least one of the study arms.



The doses of megestrol acetate assessed were as follows:

• 400 mg per day or less

Seventeen trials: Batterham 2001(400 mg per day); Beller 1997

(160 mg per day); Chen 1997 (160 mg per day); De Conno 1998

(320 mg per day); Feliu 1992 (240 mg per day); Fietkau 1996

(160 mg per day); Gebbia 1996 (160 mg and 320 mg per day);

Heckmayr 1992 (160 mg per day); Lai 1994 (160 mg per day);

Loprinzi 1994 (160 mg per day); Pardo 2003 (320 mg per day);

Timpone 1997 (250 mg per day); Ulutin 2002 (160 mg and 320

mg per day); Vadell 1998 (160 mg per day); Von Roenn 1994

(100 mg and 400 mg per day); Westman 1999 (320 mg per day);

Zeca 1995 (320 mg per day).

• 480 mg per day

Nine trials: Beller 1997; Bruera 1990; Bruera 1998; Erkurt 2000;

Heckmayr 1992; Loprinzi 1994; McMillan 1994; Schmoll 1992;

Vadell 1998

• 600 mg per day

Two trials: Jatoi 2004; Pardo 2003

• 750 to 800 mg per day

Eleven trials: Jatoi 2002; Timpone 1997; Loprinzi 1990b; Loprinzi

1994; Loprinzi 1999; McQuellon 2002; Oster 1994; Rowland

1996; Von Roenn 1994; Weisberg 2002; Yeh 2000

• 1280 mg per day

One trial: Loprinzi 1994

• 1600 mg per day

One trial: Tchekmedyian 1992

• One trial in children with cystic fibrosis assessed megestrol ac-

etate at a dose of 10 mg/kg per day (Marchand 2000)

Study duration

The study duration ranged from ten days to 24 weeks. One study

ran for two years (Rowland 1996) and measured survival and re-

sponse to chemotherapy as well as the effect of megestrol acetate

on anorexia-cachexia syndrome. The median trial duration time

was eight weeks. Five trials had a duration of more than 12 weeks,

(see ’Characteristics of the included studies’ table).

• Assessment at seven days (Bruera 1990)

• Assessment at ten days (Bruera 1998)

• Final assessment at two weeks (Beller 1997; De Conno 1998;

Zeca 1995)

• Assessment at three weeks (Lai 1994)

• Assessment at four weeks/one month (Chen 1997; Gebbia

1996; Heckmayr 1992; Jatoi 2002; Loprinzi 1990b; Loprinzi

1999; Pardo 2003)

• Assessment at six weeks (Fietkau 1996; Tchekmedyian 1992)

• Assessment at eight weeks/two months (Chen 1997; Feliu 1992;

Loprinzi 1994; Schmoll 1992; Weisberg 2002)

• Assessment at 12 weeks/three months (Batterham 2001; Erkurt

2000; Fietkau 1996; Jatoi 2004; Marchand 2000; McMillan

1994; McQuellon 2002; Oster 1994; Timpone 1997; Ulutin

2002; Vadell 1998; Von Roenn 1994; Westman 1999; Yeh

2000)

• Assessment at six months or more (Eubanks 2002; Rowland

1996)

M E T H O D O L O G I C A L Q U A L I T Y

The methodological quality of the included studies was assessed

using the Oxford Quality Scale (Jadad 1996). Each report was

scored independently for quality by the review authors using the

three-item scale described in the ’Methods’ section above who

agreed a ’consensus’ score. The scores for methodological quality

were generally high.

Twenty one trials (62%) scored three or more out of a maximum

of five:

Beller 1997; Bruera 1990; Bruera 1998; De Conno 1998; Eu-

banks 2002; Feliu 1992; Fietkau 1996; Jatoi 2002; Jatoi 2004;

Loprinzi 1990b; Loprinzi 1994; Loprinzi 1999; Marchand 2000;

McQuellon 2002; Oster 1994; Tchekmedyian 1992; Vadell 1998;

Von Roenn 1994; Weisberg 2002; Westman 1999; Yeh 2000.

Thirteen trials (38%) achieved a low score (two points or lower):

Batterham 2001; Chen 1997; Erkurt 2000; Gebbia 1996; Heck-

mayr 1992; Lai 1994; McMillan 1994; Pardo 2003; Rowland

1996; Schmoll 1992; Timpone 1997; Ulutin 2002; Zeca 1995.

R E S U L T S

Data from the included studies were meta-analysed in to three

groups:

• megestrol acetate versus placebo,

• megestrol acetate versus other active drug treatments,

• megestrol acetate at different doses.

they were further categorized into:

• patients with cancer,

• patients with AIDS,

• patients with other underlying pathologies.

The two new complete studies and two abstracts could not be

included in the analysis because of the drop-outs in Jatoi 2004,

the comparison of two low doses of megestrol in Ulutin 2002,



the comparison of one low dose of megestrol versus high dose in

Pardo 2003 as explained below, and the lack of information in

Gambardella 1998. Only Zeca 1995 was included in the analysis

of appetite.

To address the problem of patient attrition and loss to follow-

up, both ITT and per protocol (PP) analyses were undertaken for

each of the outcomes. Three trials were excluded from the analysis

(Jatoi 2002; Jatoi 2004; Westman 1999) because more than 50%

of patients were lost to follow-up. In addition, the cross-over trials

conducted by Bruera et al (Bruera 1990; Bruera 1998) did not

report the results from the first treatment period and, because

of the problem of carry-over effects, the data from these studies

were not included. In some cases it was not possible to perform

meta-analysis due to lack of information (Batterham 2001; Beller

1997; Chen 1997; De Conno 1998; Gebbia 1996; Oster 1994;

Tchekmedyian 1992; Weisberg 2002; Westman 1999; Yeh 2000;

).

Only three of five intended outcome measures were analyzed:

1) appetite increase, expressed as a dichotomous variable (number

of patients who experience appetite increase),

2) Weight gain, expressed both as a dichotomous and continuous

variable in kg/day at the end of the treatment compared with the

baseline, and

3) Improvement in quality of life (QoL) analysed as a dichoto-

mous variable (number of patients who experienced improved

QoL, measured in different and validated scales). Basically, qual-

ity of life was assessed by different scales and derived by different

methods.

No data were available for the analysis of mid-arm circumference,

triceps skin fold thickness, appetite increase (calorific intake ex-

pressed as calories/day) and QoL expressed as a continuous vari-

able.

Megestrol acetate versus placebo

The overall results have shown improvement in appetite for pa-

tients treated with megestrol acetate (RR = 2.76 (95% CI 1.65 to

4.61)) (Comparison 01 01). The only subcategory that could be

analyzed was cancer patients (Loprinzi 1990b; Erkurt 2000; Feliu

1992; Lai 1994; Schmoll 1992; Zeca 1995). Both subcategories

AIDS and other underlying pathologies could not be analyzed be-

cause there was only one trial included in each one.

For cancer patients a statistically significant benefit was described

in appetite improvement (RR 3.03, 95% CI 1.83 to 5.01) and

weight gain as a continuous variable (WMD = 3.56 (95% CI 1.27

to 5.85)) (Comparison 01 02). The same direction and significance

of the results was seen with weight gain as a dichotomous variable

(RR = 2.14 (95% CI 1.41 to 3.24)) (Comparison 01 03).

Six trials (four on cancer sub-category and two on AIDS) were

included for the comparison of the effect of megestrol acetate and

placebo on health-related quality of life (HRQoL) and no signif-

icant results were seen. Clinical and statistical heterogeneity were

detected and explained by severity of illness, treatment duration

and different scales (P < 0.0001) (Comparison 01 04). Three tri-

als in the subcategory of patients with cancer have used the per-

formance status and Karnofsky Index (KI), and one the Linear

Analog Self Assessment, nine items (LAS). Studies included in the

AIDS subcategory used KI and LAS.

A random effect analysis was carried out and a P value < 0.1 was

found. A single outlier study (Erkurt 2000) can make a very large

contribution to the statistical heterogeneity, resulting in a conclu-

sion that there is heterogeneity in both appetite and weight gain

when the studies yield a “credible” conclusion. The pooled RR may

be affected by Erkurt’s study, which had an enormous treatment

effect. The pooled value in fact is dissimilar to individual values

from all studies. Erkurt´ s quality study was low. The analysis and

interpretation of data were difficult to understand and regarding

QoL was excluded from the analysis due to the studies using an

un-validated instrument for its measurement.

Loprinzi 1990b, showed the largest pooled RR when we looked at

the analysis of weight gain as a dichotomous variable. The authors

reported that a percentage of patients gained at least 15 lb after

they were given a high dose of MA. The data were obtained by two

sources: patient-recorded home weights and institution weights.

We have included the highest level of weight gain reported . This

study was given five points as a quality score.

Megestrol acetate versus other drugs

Five of seven identified studies comparing megestrol acetate with

other drugs were pooled for the analysis. Three trials in cancer

subcategory (Chen 1997; Lai 1994; Loprinzi 1999) and two in

AIDS (Batterham 2001; Timpone 1997). Loprinzi et al have com-

pared megestrol acetate to fluoxymesterone and dexamethasone.

To analyse this trial we divided the total number of patients in-

cluded in the megestrol group by two. In other words, the num-

ber of megestrol patients in each comparison was taken to be 79

instead of 158. This method allowed us to perform the analysis.

Jatoi 2002 and Jatoi 2004 were excluded due to the high rate of

drop-outs.

When we looked at the overall results, megestrol acetate did not

show benefits in terms of appetite improvement in comparison

to other drugs (RR = 1.15 (95% CI 0.75 to 1.76)) (Comparison

02 01), and results were inconclusive for weight gain (RR = 1.29

(95% CI 0.94 to 1.96) (Comparison 02 03).

Two studies (Lai 1994; Loprinzi 1999a) included in the analysis

have measured HRQOL as an outcome using two different in-

struments. The first one used the K I and Loprinzi used Spitzer

QL index. No significant results were found (RR = 1.08 (95% CI

0.80 to 1.45)) (Comparison 02 04).

There was not enough data to compare megestrol acetate versus

other drugs in HIV/AIDS and other underlying pathology pa-

tients.

Different dose levels of megestrol acetate



In order to perform the meta-analysis, we defined 400 to 480 mg/d

as the cut off value. This was the most frequently reported dose by

authors. Then, we compared this dose to high doses (=>800 mg/d)

and to low doses (<400 to 480 mg/d). In the first group only two

trials could be analysed (Loprinzi 1994; Schmoll 1992). In the

second group two trials, out of four, were included in the analysis

(Heckmayr 1992; Loprinzi 1994). We excluded the Gebbia 1996

and Ulutin 2002 studies from this analysis because they used only

low doses and Pardo 2003 did not meet the criteria to include in

the analysis. The results of the meta-analysis were not significant.

Study withdrawals and dropouts

Only the studies who reported the total number of drop-outs and

withdrawals in each arm were included. There were 224/1115 in

the megestrol acetate group and 207/886 in the placebo group

of all the analyzed categories. Only one study (Oster 1994) re-

ported withdrawals due to lack of efficacy of treatment. A total of

29/1596 in the treated group and 24/1143 in the placebo group

were withdrawals due to adverse effects in this update including

the study of Ulutin 2002. The number of patients who suffer any

side effect was analyzed and those studies that reported toxicity

scores were also checked. The two abstracts included reported no

side-effects.

Drug safety, impotence in men, edema of the lower limbs, deep

vein thrombosis and gastrointestinal intolerance were the most

frequently reported adverse effects observed in the studies. None

of the differences between treatment and placebo groups were

found to be statistically significant, except for the occurrence of

edema, which occurred with greater frequency in patients receiving

megestrol acetate (RR = 1.74 (95% CI 1.29 to 2.35)) (Comparison

01 05).

Sensitivity analysis

This 2006 update does not show any change to the sensitivity

analysis from the previous review.

The sensitivity analysis was undertaken with studies where cancer

patients received more than six weeks of megestrol acetate versus

placebo. Two outcomes were analyzed: appetite improvement and

weight gain. We observed an overall benefit in both outcomes of

the treated group. Appetite improvement showed a RR = 3.21

(95% CI 1.54 to 6.70) (Comparison 03 01) and weight gain a RR

= 1.86 (95% CI 1.31 to 2.63) (Comparison 03 02).

Another subgroup analysis was performed considering method-

ological quality of the studies. The group with high Oxford Qual-

ity Scores (Quality Score of three, four or five) showed a benefit for

the megestrol acetate in the outcome weight gain only, both as a

dichotomous and continuos variable (RR = 1.66 (95% CI 1.13 to

2.44) (Comparison 03 06); WMD = 1.87 (95% CI 1.20 to 2.54)

(Comparison 03 05). For the outcome of appetite improvement

there were not enough studies with good Oxford Quality Scores.

In the group of low methodological score, we observed an overall

benefit in the treatment group for the outcome appetite improve-

ment (RR = 3.63 (95% CI 2.06 to 6.39)) (Comparison 03 04)

and weight gain (RR = 2.49 (95% CI 1.45 to 4.27)) (Comparison

03 06).

D I S C U S S I O N

This updated review does not provide any additional information

on this treatment as the two new studies that were included did

not provide data of any significance Jatoi 2004; Ulutin 2002).

Two systematic reviews have been undertaken recently. A system-

atic review by Maltoni 2001 assessed the efficacy of high dose

progestins for the treatment of anorexia cachexia syndrome in pa-

tients with hormone-independent tumours. This review included

15 randomized clinical trials and more than 2000 patients. The

authors concluded that high-dose progestins improve appetite and

weight, but could not define optimal dose, duration of treatment

or the impact on quality of life. The review by Ruiz-García etal. (Ruiz-Garcia 2002) evaluated the efficacy of megestrol acetate

versus placebo in patients with cancer and anorexia cachexia syn-

drome. Eight trials (719 patients) were included in the review and

found that megestrol acetate was associated with a slight weight

gain at doses of 240 mg per day or less. No statistically significant

effect was observed with higher doses.

The aim of the present update was to assess the efficacy, effec-

tiveness and safety of megestrol acetate for the management of

anorexia-cachexia syndrome, a common clinical problem that sub-

stantially impacts upon the quality of life and survival of affected

patients. Although the number of randomised trials retrieved was

71, only 34 of them were included for the analysis and 12 received

a high quality score (quality scale score of four or five). The to-

tal number of patients was 4826. However, we could not include

more than 50% of the studies in the analysis. Data was available

from only 19 studies.

There was consistency between this review and results reported by

the majority of other similar studies. This review confirms that

Megestrol acetate is a good choice to increase appetite and weight

gain in cancer patients compared to placebo. The improvement

of the nutritional status by anthropometric changes could not be

assessed due to lack of information.

Although some authors have suggested that there may be a ten-

dency towards greater efficacy with higher doses, this update

showed that clinical effects of megestrol acetate appear not to be

dose-related.

When we analysed the improvement of QoL we found great

heterogeneity between studies. Jatoi 2000 had described many

methodological issues related to QoL measurement relevant to ad-

dress in order to explain clinical heterogeneity:

a) different types of instruments,

b) extensive testing to assess global QoL,



c) difficulty administering this testing led to inconclusive QoL

findings.

On the other hand some patients cannot complete quality of life

measures because they have cognitive impairments, communica-

tion deficits, are in severe distress, or because the measures are too

burdensome. The studies included in this update used ten types

of instruments with different psychometric properties.

Another factor which may explain the discordance between ap-

petite improvement and the lack of benefit on QoL, centers on

the fact that multiple symptoms converge among advanced can-

cer patients. Donnelly et al (Donnelly 1995) evaluated symptom

prevalence in 1000 such patients and found that although anorexia

had a high prevalence, it was not an isolated symptom. Nausea,

fatigue, dry mouth, pain, and a variety of other symptoms accom-

pany anorexia.

Sensitivity analysis showed that the poorest quality trials over-

estimated positive results.

Finally, a more systematic approach to the measurement of

HRQOL in these patients would be helpful in better understand-

ing and analyzing treatment effects and the impact of megestrol

acetate on patient QoL.

Although we included studies which had up to 50% dropouts, we

found a particularly high dropout rate probably due to advanced

cancer. The population studied is very sick, so they tend to suffer

substantial cancer anorexia/cachexia along with many co morbid

problems linked to advanced cancer.

The adverse event profile of megestrol acetate has shown edema to

be the only one significant difference between placebo and mege-

strol acetate, suggesting that megestrol acetate is a safe treatment

option in these patients.

A U T H O R S ’ C O N C L U S I O N S

Implications for practice

New trials located for this update have not provided additional

information to the original conclusion. Megestrol acetate may be

prescribed in patients with cancer to increase appetite and weight

gain. At the moment, there is no evidence to recommend megestrol

acetate to improve quality of life (QoL). This update has followed

the Cochrane Collaboration Guidelines to perform an unbiased

review. However, the results of a meta-analysis are influenced by

the quality of the primary studies included. Quality is difficult to

define. It could address the design, conduct and analysis of a trial,

its clinical relevance, or the quality of reporting. Studies of low

methodological quality can alter the interpretation of the benefit

of intervention. In this update 68% of the studies were assessed as

moderate or low quality trials.

Many concerns are still to be resolved. HRQoL is an important

goal in health care and cancer clinical trials and is the cornerstone

for delivery of good palliative medicine. The increasing recogni-

tion of patient autonomy means that subjective measures will be-

come more important and, in the current climate of evidence-

based medicine, such measures must be valid and reliable.

Implications for research

This update has shown that there is still a need for high quality

studies on the effectiveness of megestrol acetate in some of the

outcomes we have reviewed, e.g. HRQOL. Even though the USA’s

Federal Drug Administration has approved megestrol acetate to

be used in AIDS patients more research is needed.

P O T E N T I A L C O N F L I C T O F

I N T E R E S T

The first version of this review had evolved from an internal report

on this topic for a pharmaceutical company that produces mege-

strol acetate. This review is independent of that report and has

been prepared with the guidance of, and in line with, the require-

ments of the Pain, Palliative and Supportive Care review group.

Aside from the above project, the review authors certify that they

have no affiliations with any organisation or entity with a direct

financial interest in the subject matter of the review.

A C K N O W L E D G E M E N T S

We would like to thank the Iberoamerican Cochrane Collabora-

tion Centre for their support, particularly Marta Roque for her

critical review and Gerard Urrutia for his comments. We are grate-

ful to Dr CL Loprinzi and Paul Novotny from the Mayo Clinic;

Professor E Bruera, Department of Palliative Care and Rehabili-

tation Medicine at Cross Cancer Institute, University of Alberta,

Edmonton, and MD Anderson for supplying additional data for

this review. We would also like to thank Marcelo García Diéguez

and Nicolas Garrigue from Argentina who have helped us with the

search strategy and comments. We would like to thank Sylvia Bick-

ley (Trials Search Co-ordinator, Cochrane Pain, Palliative Care &

Supportive Care Group) for performing the bibliographic searches

in the present version of this update.

S O U R C E S O F S U P P O R T

External sources of support

• No sources of support supplied

Internal sources of support

• Instituto de Investigaciones Epidemiológicas. Academia Na-

cional de Medicina de Buenos Aires ARGENTINA



R E F E R E N C E S

References to studies included in this review

Batterham 2001 {published data only}

Batterham MJ, Garsia R. A comparison of megestrol acetate, nan-

drolone decanoate and dietary counselling for HIV associated weight

loss. International Journal of Andology 2001;24(4):232–40.

Beller 1997 {published data only}

Beller E, Tattersall M. Improved quality of life with megestrol ac-

etate in patients with endocrine-insensitive advanced cancer: A ran-

domised placebo-controlled trial. Annals of Oncology 1997;8:277–

83.

Bruera 1990 {published data only}

Bruera E, Mc Millan K. A controlled trial of megestrol acetate on

appetite, caloric intake, nutritional status, and other symptoms in

patients with advanced cancer. Cancer 1990;66:1279–82.

Bruera 1998 {published data only}

Bruera E, Scott E. Effectiveness of megestrol acetate in patients with

advanced cancer: a randomized, double-blind, crossover study. Can-

cer Prevention & Control 1998;2(2):74–8.

Chen 1997 {published data only}

Chen Hui-Chun, Wan Leung S. Effect of megestrol acetate and pre-

pulsid on nutritional improvement in patients with head and neck

cancers undergoing radiotherapy. Radiotherapy and Oncology 1997;

43:75–9.

De Conno 1998 {published data only}

De Conno F, Martini C. Megestrol acetate for anorexia in patients

with far-advanced cancer: a double-blind controlled clinical trial.

European Journal of Cancer 1998;34:1705–9.

Erkurt 2000 {published data only}

Erkurt E, Erkisi M. Supportive treatment in weight-losing cancer pa-

tients due to the additive adverse effects of radiation treatment and/or

chemotherapy. Journal of Experimental Clinical Cancer Research 2000;

19(4):431–9.

Eubanks 2002 {published data only}

Eubanks V, Koppersmith N. Effects of megestrol acetate on weight

gain, body composition, and pulmonary function in patients with

cystic fibrosis. Journal of Pediatrics 2002;140(4):439–44.

Feliu 1992 {published data only}

Feliu J, Gonzalez-Baron M. Usefulness of megestrol acetate in cancer

cachexia and anorexia. A placebo controlled study. American Journal

of Clinical Oncology 1992;15(5):436–40.

Fietkau 1996 {published data only}∗Fietkau R, Riepl M. Supportive treatment with megestrol acetate

during radio (chemo) therapy. A randomised trial. Strahlenther Onkol

1996;172:162–8.

Fietkau R, Riepl M, Kettner H, Hinke A, Sauer R. Supportive use of

megestrol acetate in patients with head and neck cancer during radio

(chemo)therapy. European journal of cancer (Oxford, England: 1990)

1997;33(1):75–9.

Gambardella 1998 {published data only}

Gambardella A, Pesce L, Bolognino P, Lombardi G, Barbieri M, Ri-

naldi C. Megestrol acetate prevents cachexia in elderly cancer patient.

Annals of oncology 1998;9, Suppl 3:72.

Gebbia 1996 {published data only}

Gebbia V, Testa A. Prospective randomised trial of two dose levels of

megestrol acetate in the management of anorexia-cachexia syndrome

in patients with metastatic cancer. British Journal of Cancer 1996;73:

1576–80.

Heckmayr 1992 {published data only}

Heckmayr M, Gatzemeier U. Treatment of cancer weight loss in

patients with advanced lung cancer. Oncology 1992;49(suppl 2):32–

4.

Jatoi 2002 {published data only}

Jatoi A, Windschitl HE. Dronabinol versus megestrol acetate versus

combination for cancer-associated anorexia: A North Central Cancer

Tratment Group Study. Journal of Clinical Oncology 2002;20(2):567–

73.

Jatoi 2004 {published data only}

Jatoi A, Rowland K, Loprinzi CL, et al.An eicosapentaenoic acid

supplement versus megestrol acetate versus both for patients with

cancer-associated wasting: a north central cancer treatment group and

National Cancer Institute of Canada Collaborative Effort. Journal of

Clinical Oncology 2004;22:2469–76.

Lai 1994 {published data only}

Lai YL, Fang FM. Management of anorexic patients in radiother-

apy: A prospective randomized comparison of megestrol and pred-

nisolone. Journal of Pain and Symptom Management 1994;9:265–8.

Loprinzi 1990b {published data only}∗Loprinzi CL, Ellison NM. Controlled trial of megestrol acetate for

the treatment of cancer anorexia and cachexia. Journal of the National

Cancer Institute 1990;82:1127–32.

Loprinzi 1994 {published data only}∗Loprinzi CL, Bernath AM. Phase III evaluation of 4 doses of mege-

strol acetate for patients with cancer anorexia and/or cachexia. On-

cology 1994;51:2–7.

Loprinzi CL, Michalak Jc, Schaid DJ, et al.Phase III evaluation of

four doses of megestrol acetate as therapy for patients with cancer

anorexia and/or cachexia. Journal of clinical oncology: official journal

of the American Society of Clinical Oncology 1993;11(4):762–7.

Loprinzi 1999a {published data only}∗Loprinzi CL, Kugler JW. Randomized comparison of megestrol ac-

etate versus dexamethasone versus fluoxymesterone for the treatment

of cancer anorexia/cachexia. Journal of Clinical Oncology 1999;17:

3299–306.

Loprinzi 1999b {published data only}

Loprinzi CL, Kugler JW. Randomized comparison of megestrol ac-

etate versus dexamethasone versus fluoxymesterone for the treatment

of cancer anorexia/cachexia. Journal of Clinical Oncology 1999;17:

3299–306.



Marchand 2000 {published data only}

Marchand V, Baker SS. Randomized, double-blind, placebo-con-

trolled pilot trial of megestrol acetate in malnourished children with

cystic fibrosis. Journal of Pediatric Gastroenterology and Nutrition

2000;31:264–9.

McMillan 1994 {published data only}

Mc Millan DC, Simpson JM. Effect of megestrol acetate on weight

loss, body composition and blood screen of gastrointestinal cancer

patients. Clinical Nutrition 1994;13:85–9.

McQuellon 2002 {published data only}

Mc Quellon RP, Moose DB. Supportive use of megestrol acetate

(MEGACE) with head/neck and lung cancer patients receiving ra-

diation therapy. International Journal of Radiation Oncology Biology

and Physics 2002;52:1180–5.

Oster 1994 {published data only}

Oster MH, Enders SR. Megestrol acetate in patients with AIDS and

cachexia. Annals of Internal Medicine 1994;121:400–8.

Pardo 2003 {published data only}∗Pardo J, Mena AM, Montsech L. Megestrol acetate for anorexia

in lung cancer patients undergoing radiation therapyA randomized

trial comparing the efficacy of two different doses in 130 patients.

Proceedings for the American Society for Clinical Oncology 2003;22

(abstr 3076):765.

Rowland 1996 {published data only}

Rowland KM, Loprinzi CL. Randomized double-blind placebo-con-

trolled trial of cisplatin and etoposide plus megestrol acetate/ placebo

in extensive-stage small-cell lung cancer: A North Central Cancer

Treatment Group Study. Journal of Clinical Oncology 1996;14:135–

41.

Schmoll 1992 {published data only}∗Schmoll E. Risks and benefits of various therapies for cancer

anorexia. Oncology 1992;49:43–5.

Schmoll E, Wilke H, Thole R, et al.Megestrol acetate in cancer

cachexia. Seminars in oncology 1991;18(1 Suppl 2):32–4.

Tchekmedyian 1992 {published data only}

Tchekmedyian NS, Hickman M. Megestrol acetate in cancer

anorexia and weight loss. Cancer 1992;69:1268–74.

Timpone 1997 {published data only}

Timpone JG, Wright DJ. The safety and pharmacokinetics of single-

agent and combination therapy with megestrol acetate and dronabi-

nol for the treatment of HIV wasting syndrome. AIDS Research and

Human Retroviruses 1997;13:305–15.

Ulutin 2002 {published data only}

Ulutin HC, Arpaci F, Pak Y. Megestrol acetate for cachexia and

anorexia in advanced non-small cell lung cancer: a randomized study

comparing two different doses. Tumori 2002;88:277–80.

Vadell 1998 {published data only}

Vadell C, Segui MA. Anticachectic efficacy of megestrol acetate at dif-

ferent doses and versus placebo in patients with neoplastic cachexia.

American Journal of Clinical Oncology 1998;21:347–51.

Von Roenn 1994 {published data only}

Von Roenn JH, Armstrong D. Megestrol acetate in patients with

AIDS-related cachexia. Annals of Internal Medicine 1994;121:393–9.

Weisberg 2002 {published data only}

Weisberg J, Wanger J. Megestrol acetate stimulates weight gain

and ventilation in underweight COPD patients. Chest 2002;121(4):

1070–8.

Westman 1999 {published data only}

Westman G, Bergman B. Megestrol acetate in advanced, progressive,

hormone-insensitive cancer. Effects on the quality of life: a placebo-

controlled, randomised, multicentre trial. European Journal of Cancer

1999;35:586–95.

Yeh 2000 {published data only}

Yeh SS, Wu SY. Improvement in quality of life measures and stim-

ulation of weight gain after treatment with megestrol acetate oral

suspension in geriatric cachexia: Results of a double-blind, placebo-

controlled study. Journal of the American Geriatric Society 2000;48

(5):485–92.

Zeca 1995 {published data only}

Zeca E, Martini C, Venturino P, Tedeschi M, Ventafrida V, De Conno

F. Efficacy of Megestrol Acetate on Anorexia in patients with ad-

vanced non hormone-related tumors: A double-blind placebo con-

trolled clinical trial. European Journal of Cancer 1995;31 A:S261–

S262.

References to studies excluded from this review

Macbeth 1994

Macbeth FR, Gregor A, Cottier B. A randomised study of megestrol

acetate (MA) and prednisolone (P) for anorexia and weight loss in

patients with lung cancer.

McMillan 1999

Mc Millan DC, Wigmore SJ. A prospective randomised study of

megestrol acetate and ibuprofen in gastrointestinal cancer patients

with weight loss. British Journal of Cancer 1999;79:495–500.

Yeh 2004∗Yeh S, Hafner A, Chang C, et al.Risk Factors Relating Blood Mark-

ers of Inflammation and Nutritional Status to Survival in Cachec-

tic Geriatric Patients in a Randomized Clinical Trial. Journal of the

American Geriatrics Society 2004;52:1708–12.

Additional references

Alexander 1993

Alexander HR, Norton JA. Pathophisiology of cancer cachexia. In:

DoyleD, HanksGWC, MacDonaldN editor(s). Textbook of palliative

medicine. 3rd Edition. Oxford: Oxford University Press, 1998.

Argilés 2001

Argilés JM, Meijsing SH, Pallares-Trujillo J. Cancer cachexia. A ther-

apeutic approach. Medical Research Review (US) 2001;21:83–101.

Balog 1998

Balog DL, Epstein ME, Amidio-Groton MI. HIV wasting syndrome:

Treatment update. Annals of Pharmacotherapy 1998;32(4):446–58.

Barber 1999

Barber MD, Ross JA, Voss AC, et al.The effect of an oral nutritional

supplement enriched with fish oil on weight-loss in patients with

pancreatic cancer. British Journal of Cancer 1999;81:80–6.

Bruera 1992

Bruera E. Clinical management of anorexia and cachexia in patients

with advanced cancer. Oncology 1992;49(2):35–42.



Donnelly 1995

Donnelly S, Walsh D. The symptoms of advanced cancer: Identifi-

cation of clinical and research priorities by assessment of prevalence

and severity. Journal of Palliative Care 1995;22:27–32.

Jadad 1996

Jadad A, Moore RA, Carrol D, et al.Assessing the quality of reports on

randomized clinical trials: Is blinding necessary?. Controlled Clinical

Trials 1996;170:1–12.

Jatoi 2000

Jatoi A, Kumar S. On appetite and its loss. Journal of Clinical Oncology

2000;18:2930–2.

Loprinzi 1990a

Loprinzi C, Ellison NM, Goldberg RM, et al.Alleviation of cancer

anorexia and cachexia: Studies of the Mayo Clinic and the North

Central Cancer Treatment Group. Seminars in oncology 1990;17(6

suppl 9):8–12.

Loprinzi 1999

Loprinzi CL, Kugler JW, Sloan JA. Randomized comparison of Mege-

strol Acetate versus dexamethasone versus fluoxymesterone for the

treatment of cancer anorexia/cachexia. Journal of Clinical Oncology

1999;17:3299–306.

Maltoni 2001

Maltoni M, Nanni O, Scarpi E, et al.High-dose progestins for the

treatment of cancer anorexia-cachexia syndrome: A systematic review

of randomised clinical trials. Annals of Oncology 2001;12(3):289–

300.

Mantovani 1998

Mantovani G, Maccio A, Lai P, et al.Cytokyne activity in cancer-

related anorexia/cachexia: role of megestrol acetate and medroxypro-

gesterone acetate. Seminars in oncology 1998 (US);25(2 suppl 16):

45–52.

Nelson 1994

Nelson KA, Walsh D, Sheehan FA, et al.The cancer anorexia-cachexia

syndrome. Journal of Clinical Oncology 1994;12:213–25.

Ruiz-Garcia 2002

Ruiz-Garcia V, Juan O, Perez Hoyos S, et al.Megestrol acetate: a sys-

tematic review usefulness about the weight gain in neoplastic patients

with cancer. Medicina Clinica (Barcelona) 2002;119(5):166–70.

Splinter 1992

Splinter TA. Cachexia and cancer: a clinician´ s view. Annals of On-

cology 1992;3(3):25–7.

Tchekmedyian 1986

Tchekmedyian NS, Tait N, Aisner J. High dose megestrol acetate

in the treatment of postmenopausal women with advanced breast

cancer. Seminars in oncology 1986;13(4):20–5.

Von Roenn 1996

Von Roenn JH, Knopf K. Anorexia/cachexia in patients with HIV:

lessons for the oncologist. Oncology 1996;10(7):1049–56.

Wigmore 1997

Wigmore SJ, Fearon KCH, Maingay JP, et al.Down-regulation of

the acute-phase response in patients with pancreatic cancer cachexia

receiving oral eicosapentaenoic acid is mediated via suppression of

interleukin-6. Clinical Science 1997;92:215–21.

∗Indicates the major publication for the study

T A B L E S

Characteristics of included studies

Study Batterham 2001

Methods Randomised controlled

In a tertiary referral hospital, Sydney

Participants 15 HIV pts

a) 4 M mean age 46 yrs

b) 6 M mean age 44 yrs

c) 5 M mean age 42 yrs, five completed and then randomized three to nandrolone and two to megestrol

Interventions a) MA 400 mg/d orally

b) nandrolone decanoate 100 mg/fortnight IM injection

c) diet counseling

duration 12 weeks

Outcomes Weight

Appetite VAS ten points score

0 = poor appetite

10 = good appetite



Characteristics of included studies (Continued )

Dietary intake %

Notes 12 weeks of treatment

QS = 2

Allocation concealment B – Unclear

Study Beller 1997

Methods Double blind,

randomised controlled

multicentre (15), stratified by institution and whether receiving any anti tumor treatment

Participants 240 cancer pts

a) 81 pts = 53M + 28F

(nine pts = 50 yrs, 49 pts = 51 to 70 yrs, 23pts = > 71 yrs)

b) 80 pts = 52M + 28F

(seven pts = lower than 50 yrs, 52 pts = 51 to 70 yrs, 21 pts = >70 yrs)

c) 79 pts = 54M + 25F

(12 pts = 50 yrs, 51 pts = 51 to 70 yrs, 16 pts = >70 yrs)


b) MA 160 mg/d

c) placebo

Outcomes QoL five linear analogue self assessment scales (LASA) asked patients about five factors: physical well being,

mood, pain, nausea and vomiting, and appetite.

and a LASA uniscale of overall QoL and the Spitzer QL

- Index, completed by the clinician

- Appetite (LASA score) Nutritional status

- weight

- triceps skinfold

- mid-arm circumference

Notes Two weeks of treatment

QS = 4

Allocation concealment A – Adequate

Study Bruera 1990

Methods Double blind, cross over randomised controlled

Participants 40 advanced cancer pts

31 included pts = 25M + 6F

Interventions a) MA 480 mg/d

b) placebo

Outcomes Appetite, subjective energy level, well being depression, and pain were assessed with VAS (0 to 100 mm)

Nutritional status, weight, triceps skin fold, arm and calf circumference.

Caloric intake, in calories

Notes Seven days first phase

QS = 3


Study Bruera 1998

Methods Cross over




double blind

randomised

controlled

Participants 84 advanced cancer pts

47M + 37F

mean age 62 yrs


b) placebo

Outcomes Appetite (VAS)

weight

triceps skinfold

QoL Functional Living Index Cancer (FLIC)

Notes Ten days of treatment

QS = 4


Study Chen 1997



a) 48 pts = 36M + 12F

mean age 50 yrs

b) 41 pts = 30M + 11F mean age 52 yrs

c) 40 pts = 30M + 10F mean age 51 yrs


b) cisapride 10 mg/d

c) placebo

Outcomes Weight

Appetite score zero to five

Notes Four and eight weeks of treatment

during a full course of radiotherapy

QS = 2


Study De Conno 1998

Methods Double blind



a) 21 pts = 15M + 6F mean age 63 yrs



b) placebo

Outcomes Appetite

Score zero to ten

Weight

QoL Therapy Impact Questionnaire (TIQ)

Notes 14 days of treatment

QS = 3





Study Erkurt 2000




b) 57 pts = 45M + 5F

mean age 57 yrs


b) placebo

Outcomes Weight

Appetite score zero to five

QoL Eastern Cooperative Oncology Group Performance status (ECOG PS)

Notes Three months of treatment

46 pts during RT, and four at the end of RT of MA group

QS = 2


Study Eubanks 2002

Methods Double blind randomised controlled

Participants 17 cystic fibrosis pts

a) ten pts = 5M + 4F range age six to 18 yrs.

1F 35 yrs

b) 7pts = 3F + 4M range age six to 15 yrs

Interventions a) MA 10 mg/kg per day

b) placebo

Outcomes Weight

Triceps skinfold

Mid arm circumference

Notes Six months of treatment

QS = 4


Study Feliu 1992





b) 74 pts = 55M + 7F

mean age 58 yrs


b) placebo

Outcomes Weight

Appetite VAS score

QoL performance status KI

Notes Two months of treatment

QS = 4





Study Fietkau 1996




61 pts =

a) 31pts = 25M + 6F mean age 52 yrs

b) 30 pts = 24M + 6F

mean age 48 yrs


b) placebo

Outcomes Nutritional status weight

QoL index according to Padilla Index

Notes Six weeks of treatment during and up six weeks following radiotherapy

Pts were stratified according oral feeding versus gastrostomy

QS = 3


Study Gambardella 1998

Methods NO DATA AVAILABLE

Participants NO DATA AVAILABLE

Interventions NO DATA AVAILABLE

Outcomes NO DATA AVAILABLE

Notes NO DATA AVAILABLE

Allocation concealment D – Not used

Study Gebbia 1996



a) 62 pts = 46M + 16F

mean age 63 yrs

b) 60 pts = 42M + 18F

mean age 65 yrs


b) MA 320 mg/d

Outcomes Appetite, Symptom Distress Scale (SDS)

Weight

Performance Status


QS = 2


Study Heckmayr 1992


Participants 66 cancer




a) 33 pts = 24M + 9F

mean age 65 yrs



b) MA 480 mg/d

Outcomes Appetite (subjective ten point scale)

Weight

Notes Four weeks of treatment

QS = 1


Study Jatoi 2002


randomised controlled multicentre (20)


a) 159 pts = 103M + 56F mean age 65 yrs b)152 pts = 100M + 52F

mean age 67 yrs


Interventions a) MA 800 mg/d liquid suspension +2 capsules placebo

b) Dronabinol capsules 2.5 mg orally x 2 + liquid placebo

c) MA suspension 800 mg/d + Dronabinol capsules 2.5 mg x 2

Outcomes Appetite (validated questionnaires)

Weight

QoL Functional Assessment of Anorexia/Cachexia Therapy (FAACT) instrument uniscale and thirteen item

Notes Duration more than four weeks of treatment

QS = 3


Study Jatoi 2004

Methods Double blind randomised controlled multicentre (26)


a) 140 pts = 97M + 43F

mean age 65 yrs

b) 141 pts = 104M + 37F

mean age 66 yrs

c) 140 pts = 92M + 48F

mean age 66 yrs

Interventions a) MA 600 mg/d liquid suspension + isocaloric, isonitrogenous placebo cans

b) EPA supplement, two cans/d + placebo liquid suspension

c) EPA supplement two cans/d plus MA liquid suspension 600 mg/d orally in combination

Outcomes Weight

Appetite (NCCTG questionnaire and FAACT)

QoL (single-item Uniscale)

Notes Duration more than three months

QS = 4





Study Lai 1994


Participants 52 Cancer pts


b) 17 pts = 17F

mean age 60 yrs



b) Prednisolone 30 mg/d

c) placebo x 3

Outcomes Weight

Appetite, self report

QoL performance status KI

Notes Duration 21 days

QS = 2


Study Loprinzi 1990b



Participants 133 Cancer pts


b) 66 pts = 44M + 22F

mean age 67 yrs


b) placebo

Outcomes Weight

Appetite

Notes One month of treatment

QS = 5


Study Loprinzi 1994




b) 86 pts = 54M + 32F

mean age 67 yrs


d) 83 pts = 54M + 29F mean age 66 yrs


b) MA 480 mg/d

c) MA 800 mg/d

d) MA 1280 mg/d

Outcomes Weight

Appetite

Notes Median 66 days of treatment




QS = 3


Study Loprinzi 1999a

Methods Randomised controlled multicentre


a) 79 pts = 55M + 30F

mean age 66 yrs



b) dexamethasone 3 mg/d

Outcomes Appetite

Weight

QoL (uniscale)


QS = 3


Study Loprinzi 1999b

Methods Randomised controlled multicentre


a) 79 pts = 54M + 29F

mean age 66 yrs



b) fluoxymesterone 20 mg/d

Outcomes Appetite

Weight

QoL (uniscale)


QS = 3


Study Marchand 2000


cross over

controlled

randomised

Participants 12 cystic fibrosis children pts

a) six pts

b) six pts

mean age seven, four yrs, 9F + 3M

Interventions a) MA 10 mg/ kg/d x 2

b) placebo

Outcomes Appetite

Weight

Triceps skinfold






QS = 3


Study McMillan 1994



a) 20 pts

mean age 73 yrs

b) 18 pts

mean age 70 yrs


b) placebo

Outcomes Weight


QS = 2


Study McQuellon 2002



a) 28 pts = 20M + 8F, mean age 60 yrs

b) 28 pts = 16M + 12F mean age 65 yrs (one excluded due to positive findings in bone scan)

Interventions a) MA 800 mg/ d suspension

b) placebo suspension 20 ml

Outcomes Weight

QoL FACT


QS = 3


Study Oster 1994


randomised controlled multicenter (13)




Interventions a) MA 800 mg/d suspension

b) placebo, suspension

Outcomes Appetite

Weight

Triceps skinfold

Mid arm circunference

Performance status KI





QS = 5


Study Pardo 2003

Methods Randomized controlled

Participants 130 cancer patients

a) 64 pts = 58M + 6F mean age 66.8 yrs

b) 66 pts = 62 M + 4F mean age 65.3 yrs

Interventions a) MA 320mg/day

b) MA 600mg/day

Outcomes Appetite


QS = 1


Study Rowland 1996



a) 122 pts = 56M + 44F

b) 121 pts = 64M + 36F


b) placebo

Outcomes Appetite questionnaire

QoL VAS uniscale

Notes Mean duration four months and up to two years

QS = 2


Study Schmoll 1992



a) 29 pts = 18M + 11F

mean age 60 yrs

b) 28pts = 16M + 12F mean age 58 yrs



b) placebo

c) MA 480 mg/d

Outcomes Appetite

Weight

Notes a) median duration eight weeks of treatment

b) median duration six weeks

c) median duration seven weeks

QS = 2





Study Tchekmedyian 1992




a) 49 pts = 28M + 9F

mean age 63 yrs

b) 40 pts = 18M + 12F

mean age 64 yrs

Interventions a) MA 1600 mg/d, ten tablets a day, in divided doses

b) placebo ten tablets

Outcomes Appetite, categoric scale of five levels

QoL LAS, 29 items

Weight

Triceps skinfold

Mid arm circunference

Notes Six weeks of treatment

QS = 4


Study Timpone 1997

Methods Randomised controlled multicenter (9)



b) 12 pts = 10M + 2F

mean age 39 yrs


d) 13 pts = 12M + 1F mean age 40 yrs

Interventions a) MA 750 mg/d, tablets x 1

b) Dronabinol 5 mg/d, tablets x 2

c) a) + b)

d) MA 250 mg/d + Dronabinol 5 mg/d, two tablets

Outcomes Weight

QoL KI


QS = 2


Study Ulutin 2002

Methods Randomised controlled study


a) 59 pts = 48M + 11F

mean age 56 (range 38 to 72)

b) 60 pts = 47M + 13F

mean age 58 (range 40 to 74)


b) MA 320 mg/d orally in two divided doses 12 hrs apart

Outcomes Weight

Appetite (Symptom Distress Scale)




QoL (ten point scale) based on patient statements

Notes Three month duration treatment

QS = 2


Study Vadell 1998

Methods Double blind randomised controlled multicenter (nine)





Interventions a) MA 480 mg/d, three tablets

b) placebo, three tablets

c) MA 160 mg/d, one tablet + placebo two tablets

Outcomes Weight


Triceps skinfold

QoL KI


QS = 3


Study Von Roenn 1994

Methods Double blind randomised controlled multicenter


a) 75 pts = 75M

mean age 38 yrs

b) 75 pts = 75M mean age 39 yrs


d) 38 pts = 38M mean age 38 yrs

Interventions a) MA 800 mg/d, suspension

b) MA 400 mg/d, suspension

c) MA 100 mg/ d, suspension

d) placebo, suspension

Outcomes Weight

Appetite


Triceps skinfold

QoL, by Linear Analog Self Assessment questionnaire


QS = 4


Study Weisberg 2002

Methods Double blind randomised controlled multicenter (18)

Participants 145 COPD pts

a) 72 pts = 46M + 26F




mean age 68 yrs




Outcomes Weight

Triceps skinfold


Appetite

Notes Eight weeks of treatment

QS = 4


Study Westman 1999

Methods Double blind randomised controlled multicenter (15)



b) 127 pts = 64M + 63F

mean age 69 yrs

Interventions a) MA 320 mg/d, tablets

b) placebo, tablets

Outcomes Weight

QoL EORTC QLQ-C30

Appetite


QS = 5


Study Yeh 2000


Participants 69 geriatric pts





Outcomes Weight

Appetite

QoL VAS nine items


QS = 5


Study Zeca 1995


randomized controlled


a) 16 pts (no data available of age and sex)



b) 17 pts

b) 17 pts

Interventions a) 320 mg/day, tablets

b) placebo

Outcomes Appetite measured in a categoric numeric Scale

Weight

Performance status (Karnofsky)

Notes A) phase A 14 days of treatment

B) phase B, open of 76 days of treatment

QS = 2


Pts = patients = females (F) + males (M)

VAS = Visual Analog Self reported scale

*** = CHRONIC OBSTRUCCION PULMONARY DISEASE (COPD)

KI = Karnofsky Index

yrs = Years

M = male

F = female

MA - Megesterol acetate

QS = Quality Score (Oxford Quality Scale)

Characteristics of excluded studies

Study Reason for exclusion

Macbeth 1994 This study was unpublished and closed early due to the numbers of withdrawals (> 50% of death in the megestrol

arm)

McMillan 1999 This study was excluded because the two arms of the treated patients were receiving megestrol acetate

Yeh 2004 This study involved the same participants as Yeah 2000, in which they measured different outcomes

A D D I T I O N A L T A B L E S

Table 01. Patient condition and numbers recruited to each trial

Study

Lung

cancer

Gastroint

& pancreas

Head &

neck cancer

Gynecolog-

ical cancer

Other

cancer AIDS COPD

Cystic

fibrosis Elderly

Bruera 1990 15 14 11

Loprinzi

1990

42 53 38

Feliu 1992 75 36 9 30

Heckmayr

1992

66

Schmoll

1992

91

Tchekme-

dyan 1992

27 23 4 35



Table 01. Patient condition and numbers recruited to each trial (Continued )

Study

Lung

cancer

Gastroint

& pancreas

Head &

neck cancer

Gynecolog-

ical cancer

Other

cancer AIDS COPD

Cystic

fibrosis Elderly

Lai 1994 8 44 0

Loprinzi

1994

130 111 101

McMillan

1994

26 12

Oster 1994 100

Von Roenn

1994

270

Fietkau

1996

64

Gebbia

1996

50 22 40 10

Rowland

1996

243

Beller 1997 48 106 18 68

Chen 1997 129

Timpone

1997

50

Bruera 1998 37 20 3 24

De Conno

1998

21 10 6 5

Vadell 1998 75 35 5 8 27

Loprinzi

1999

191 170 114

Westman

1999

74 126 4 22 29

Erkurt 2000 42 5 42 26

Marchand

2000

12

Yeh 2000 69

Batterham

2001

15

Eubanks

2002

17

Jatoi 2002 208 139 122

Mc Quellon 33 23



Table 01. Patient condition and numbers recruited to each trial (Continued )

Study

Lung

cancer

Gastroint

& pancreas

Head &

neck cancer

Gynecolog-

ical cancer

Other

cancer AIDS COPD

Cystic

fibrosis Elderly

2002

Weisberg

2002

145

Ulutin HC

2002

119

Pardo 2003 130

Jatoi 2004 166 141 114

Zeca 1995 33

Total 1792 1045 347 74 890 435 145 29 69

Table 02. EMBASE

No Search term

1. Acquired Immunodeficiency Syndrome/

2. acquired immunodeficiency syndrome.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title,

device manufacturer, drug manufacturer name]

3. AIDS.ab,ti.

4. exp Neoplasm/

5. (neoplasm$ or cancer$ or tumor$ or tumour$ or carcinoma$ or malignan$).mp. [mp=title, abstract, subject headings, heading

word, drug trade name, original title, device manufacturer, drug manufacturer name]

6. Terminally Ill patient/

7. Terminal Care/

8. ((terminal adj6 ill$) or (terminal$ adj6 care)).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original

title, device manufacturer, drug manufacturer name]

9. (end adj6 life).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer,

drug manufacturer name]

10. or/1-9

11. anorexia-cachexia syndrome.mp.

12. Anorexia/

13. Cachexia/

14. Weight Reduction/

15. (anorexi$ or cachexi$ or cachectic or (weight adj4 loss) or wasting).mp. [mp=title, abstract, subject headings, heading word,

drug trade name, original title, device manufacturer, drug manufacturer name]

16. emaciat$.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug

manufacturer name]



Table 02. EMBASE (Continued )

No Search term

17. or/11-16

18. Megestrol Acetate/

19. megace$.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug

manufacturer name]

20. (megestrol adj acetate).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device

manufacturer, drug manufacturer name]

21. or/18-20

22. 10 and 17 and 21

23. 22 (88)

24. limit 23 to yr=“2002 - 2006” (24)

Table 03. Cochrane Pain, Palliative and Supportive Care Group Trials register

Search strategy

(Acquired Immunodeficiency Syndrome“[All Fields] OR (acquired immunodeficiency syndrome”[MeSH Terms] OR AIDS

[Text Word])) ((neoplasms“[MeSH Terms] OR Neoplasm [Text Word]) OR cancer [Text Word])) ((end of life”[All Fields] OR

(terminally ill“ [MeSH Terms] OR Terminally ill [Text Word])) OR (terminal care”[MeSH Terms] OR Terminal care[Text Word]))

(cachexia“[MeSH Terms] OR cachexia [Text Word]) (megestrol acetate” [MeSH Terms] OR megestrol acetate [Text Word])

A N A L Y S E S

Comparison 01. Megestrol acetate vs placebo (ITT)

Outcome titleNo. of

studies

No. of

participants Statistical method Effect size

01 Appetite improvement 10 885 Relative Risk (Random) 95% CI 2.76 [1.65, 4.61]

02 Weight gain 10 843 Weighted Mean Difference (Random) 95% CI 2.78 [1.61, 3.95]

03 Weight gain 10 1246 Relative Risk (Random) 95% CI 1.95 [1.44, 2.62]

04 Quality of life 6 952 Relative Risk (Random) 95% CI 1.52 [0.87, 2.66]

05 Side effects 11 1767 Relative Risk (Random) 95% CI 1.74 [1.29, 2.35]

Comparison 02. Megestrol acetate vs other drugs (ITT)

Outcome titleNo. of

studies

No. of


01 Appetite improvement 3 514 Relative Risk (Random) 95% CI 1.15 [0.75, 1.76]

02 Weight gain 5 598 Weighted Mean Difference (Random) 95% CI 3.82 [0.06, 7.57]

03 Weight gain 4 524 Relative Risk (Random) 95% CI 1.29 [0.94, 1.76]

04 Quality of life 3 514 Relative Risk (Random) 95% CI 1.08 [0.80, 1.45]



Comparison 03. Sensitivity analysis

Outcome titleNo. of

studies

No. of


01 Appetite improvement,

treatment duration

4 489 Relative Risk (Random) 95% CI 3.21 [1.54, 6.70]

02 Weight gain, treatment

duration


03 Weight gain, treatment

duration

4 393 Weighted Mean Difference (Random) 95% CI 4.54 [0.43, 8.66]

04 Appetite improvement, study

quality


05 Weight gain, study quality 6 499 Weighted Mean Difference (Random) 95% CI 3.53 [1.43, 5.62]

06 Weight gain, study quality 7 895 Relative Risk (Random) 95% CI 1.83 [1.35, 2.50]

I N D E X T E R M S

Medical Subject Headings (MeSH)

Acquired Immunodeficiency Syndrome [complications]; Anorexia [∗drug therapy; etiology]; Appetite Stimulants [∗therapeutic use];

Cachexia [∗drug therapy; etiology]; Megestrol Acetate [∗therapeutic use]; Neoplasms [complications]; Randomized Controlled Trials

as Topic; Syndrome

MeSH check words

Humans

C O V E R S H E E T

Title Megestrol acetate for treatment of anorexia-cachexia syndrome

Authors Berenstein EG, Ortiz Z

Contribution of author(s) ZO put forward the idea of reviewing megestrol acetate.

GB performed the search and located trials with MGD.

GB and ZO applied the inclusion/exclusion criteria, extracted the data, appraised the quality

of the trials.

Data entry into RevMan was carried out by GB.

Both review authors wrote the review.

Issue protocol first published 2003/3

Review first published 2005/2

Date of most recent amendment 20 August 2007

Date of most recent

SUBSTANTIVE amendment

23 January 2005

What’s New For the update for Issue 3, 2007 the following changes were made:

Four new studies and three abstracts were identified, two of these studies were full text and

were included in this updated review (Ulutin 2002; Jatoi 2004). These trials added 540

additional participants to the review. Two of these studies were excluded (Macbeth 1994;

Yeh 2004).

There has been no change to the previous conclusions of the review.

Date new studies sought but

none found

Information not supplied by author



Date new studies found but not

yet included/excluded


Date new studies found and

included/excluded

01 June 2006

Date authors’ conclusions

section amended


Contact address Dr Graciela Berenstein

Medical Doctor

Epidemiology Department

Alejandro Posadas National Hospital

Paraguay 1835, 3

Buenos Aires

1121

ARGENTINA

E-mail: [email protected]

Tel: +54 11 4811 4908

Fax: +54 11 4931 2558

DOI 10.1002/14651858.CD004310.pub2

Cochrane Library number CD004310

Editorial group Cochrane Pain, Palliative and Supportive Care Group

Editorial group code HM-SYMPT

G R A P H S A N D O T H E R T A B L E S



Analysis 01.01. Comparison 01 Megestrol acetate vs placebo (ITT), Outcome 01 Appetite improvement

Review: Megestrol acetate for treatment of anorexia-cachexia syndrome

Comparison: 01 Megestrol acetate vs placebo (ITT)

Outcome: 01 Appetite improvement

Study Megestrol acetate placebo Relative Risk (Random) Weight Relative Risk (Random)

n/N n/N 95% CI (%) 95% CI

01 Cancer

Batterham 2001 0/1 0/1 0.0 Not estimable

Erkurt 2000 55/58 7/57 13.7 7.72 [ 3.85, 15.49 ]

Feliu 1992 30/76 8/74 13.5 3.65 [ 1.79, 7.44 ]

Gebbia 1996 0/1 0/1 0.0 Not estimable

Lai 1994 11/20 4/19 11.2 2.61 [ 1.00, 6.80 ]

Loprinzi 1990b 24/67 16/66 15.3 1.48 [ 0.87, 2.52 ]

Schmoll 1992 37/63 6/28 13.3 2.74 [ 1.31, 5.74 ]

Zeca 1995 13/16 5/17 12.9 2.76 [ 1.28, 5.99 ]

Subtotal (95% CI) 302 263 79.9 3.03 [ 1.83, 5.01 ]

Total events: 170 (Megestrol acetate), 46 (placebo)

Test for heterogeneity chi-square=14.78 df=5 p=0.01 I² =66.2%

Test for overall effect z=4.30 p=0.00002

02 AIDS

Von Roenn 1994 181/270 19/38 17.0 1.34 [ 0.97, 1.86 ]

Subtotal (95% CI) 270 38 17.0 1.34 [ 0.97, 1.86 ]


Test for heterogeneity: not applicable


03 Other underlying pathology

Marchand 2000 6/6 0/6 3.0 13.00 [ 0.89, 189.39 ]

Subtotal (95% CI) 6 6 3.0 13.00 [ 0.89, 189.39 ]




Total (95% CI) 578 307 100.0 2.76 [ 1.65, 4.61 ]


Test for heterogeneity chi-square=30.29 df=7 p=<0.0001 I² =76.9%


0.1 0.2 0.5 1 2 5 10

Favours placebo Favours MA



Analysis 01.02. Comparison 01 Megestrol acetate vs placebo (ITT), Outcome 02 Weight gain



Outcome: 02 Weight gain

Study Megestrol acetate Placebo Weighted Mean Difference (Random) Weight Weighted Mean Difference (Random)

N Mean(SD) N Mean(SD) 95% CI (%) 95% CI

01 Cancer

Chen 1997 48 -1.71 (4.56) 40 -3.99 (5.52) 8.8 2.28 [ 0.14, 4.42 ]

De Conno 1998 21 1.06 (1.95) 21 -0.34 (1.01) 11.6 1.40 [ 0.46, 2.34 ]

Erkurt 2000 58 5.00 (6.00) 57 -5.90 (7.00) 8.3 10.90 [ 8.52, 13.28 ]

Fietkau 1996 32 -0.80 (3.60) 32 -3.20 (3.20) 10.0 2.40 [ 0.73, 4.07 ]

Loprinzi 1990b 67 1.36 (4.99) 66 -0.22 (3.01) 10.7 1.58 [ 0.18, 2.98 ]

McQuellon 2002 28 -1.22 (6.25) 29 -4.80 (4.80) 7.1 3.58 [ 0.68, 6.48 ]

Subtotal (95% CI) 254 245 56.5 3.56 [ 1.27, 5.85 ]



02 AIDS

Von Roenn 1994 75 3.54 (4.29) 38 -0.72 (2.87) 10.8 4.26 [ 2.93, 5.59 ]

Subtotal (95% CI) 75 38 10.8 4.26 [ 2.93, 5.59 ]


Test for overall effect z=6.27 p<0.00001


Eubanks 2002 10 5.30 (3.60) 7 1.50 (1.60) 7.9 3.80 [ 1.27, 6.33 ]

Weisberg 2002 72 1.20 (1.40) 73 0.60 (1.10) 12.4 0.60 [ 0.19, 1.01 ]

Yeh 2000 36 1.05 (1.00) 33 0.91 (0.68) 12.4 0.14 [ -0.26, 0.54 ]

Subtotal (95% CI) 118 113 32.7 0.65 [ -0.14, 1.44 ]



Total (95% CI) 447 396 100.0 2.78 [ 1.61, 3.95 ]



-10 -5 0 5 10

Favours Placebo Favours M A



Analysis 01.03. Comparison 01 Megestrol acetate vs placebo (ITT), Outcome 03 Weight gain





n/N n/N 95% CI (%) 95% CI

01 Cancer

Feliu 1992 21/76 5/74 7.7 4.09 [ 1.63, 10.27 ]

Lai 1994 6/20 3/19 4.9 1.90 [ 0.55, 6.54 ]

Loprinzi 1990b 11/67 1/66 2.0 10.84 [ 1.44, 81.58 ]

Rowland 1996 26/122 8/121 10.3 3.22 [ 1.52, 6.83 ]

Schmoll 1992 17/63 4/28 6.9 1.89 [ 0.70, 5.10 ]

Tchekmedyian 1992 27/49 16/40 17.4 1.38 [ 0.87, 2.17 ]

Vadell 1998 38/99 13/51 15.2 1.51 [ 0.89, 2.56 ]

Subtotal (95% CI) 496 399 64.5 2.14 [ 1.41, 3.24 ]




02 AIDS

Von Roenn 1994 127/232 8/38 12.8 2.60 [ 1.39, 4.87 ]

Subtotal (95% CI) 232 38 12.8 2.60 [ 1.39, 4.87 ]





Marchand 2000 6/6 4/6 14.3 1.50 [ 0.85, 2.64 ]

Yeh 2000 9/36 7/33 8.5 1.18 [ 0.50, 2.81 ]

Subtotal (95% CI) 42 39 22.7 1.40 [ 0.87, 2.24 ]




Total (95% CI) 770 476 100.0 1.95 [ 1.44, 2.62 ]




0.1 0.2 0.5 1 2 5 10

Favours Placebo Favours M A



Analysis 01.04. Comparison 01 Megestrol acetate vs placebo (ITT), Outcome 04 Quality of life



Outcome: 04 Quality of life


n/N n/N 95% CI (%) 95% CI

01 Cancer

Feliu 1992 26/76 10/74 18.4 2.53 [ 1.31, 4.88 ]

Lai 1994 7/20 3/19 11.6 2.22 [ 0.67, 7.34 ]

Rowland 1996 87/122 91/121 24.2 0.95 [ 0.81, 1.10 ]

Vadell 1998 18/99 7/51 16.3 1.32 [ 0.59, 2.96 ]

Subtotal (95% CI) 317 265 70.5 1.52 [ 0.79, 2.91 ]




02 AIDS

Oster 1994 5/52 6/48 12.4 0.77 [ 0.25, 2.36 ]

Von Roenn 1994 91/232 6/38 17.1 2.48 [ 1.17, 5.27 ]

Subtotal (95% CI) 284 86 29.5 1.49 [ 0.47, 4.69 ]





Subtotal (95% CI) 0 0 0.0 Not estimable



Test for overall effect: not applicable

Total (95% CI) 601 351 100.0 1.52 [ 0.87, 2.66 ]




0.1 0.2 0.5 1 2 5 10

Favours placebo Favours M A



Analysis 01.05. Comparison 01 Megestrol acetate vs placebo (ITT), Outcome 05 Side effects



Outcome: 05 Side effects

Study Megestrol acetate Placebo Relative Risk (Random) Weight Relative Risk (Random)

n/N n/N 95% CI (%) 95% CI

01 Edema

Beller 1997 4/161 0/79 1.1 4.44 [ 0.24, 81.54 ]

Bruera 1998 1/84 0/84 0.9 3.00 [ 0.12, 72.61 ]

Chen 1997 1/48 0/40 0.9 2.51 [ 0.11, 59.98 ]

Feliu 1992 7/76 3/74 5.2 2.27 [ 0.61, 8.45 ]

Loprinzi 1990b 18/67 8/66 15.6 2.22 [ 1.04, 4.74 ]

Rowland 1996 44/122 24/121 49.1 1.82 [ 1.18, 2.79 ]

Schmoll 1992 2/63 0/28 1.0 2.27 [ 0.11, 45.71 ]

Tchekmedyian 1992 8/49 6/40 9.6 1.09 [ 0.41, 2.88 ]

Vadell 1998 2/99 0/51 1.0 2.60 [ 0.13, 53.16 ]

Von Roenn 1994 14/232 4/38 8.1 0.57 [ 0.20, 1.65 ]

Weisberg 2002 11/72 4/73 7.5 2.79 [ 0.93, 8.35 ]

Total (95% CI) 1073 694 100.0 1.74 [ 1.29, 2.35 ]

Total events: 112 (Megestrol acetate), 49 (Placebo)



0.1 0.2 0.5 1 2 5 10

Favours M A Favours Placebo



Analysis 02.01. Comparison 02 Megestrol acetate vs other drugs (ITT), Outcome 01 Appetite improvement


Comparison: 02 Megestrol acetate vs other drugs (ITT)

Outcome: 01 Appetite improvement

Study Megestrol acetate Other drugs Relative Risk (Random) Weight Relative Risk (Random)

n/N n/N 95% CI (%) 95% CI

01 Cancer

Lai 1994 11/20 6/19 20.3 1.74 [ 0.81, 3.77 ]

Loprinzi 1999a 26/79 64/159 41.5 0.82 [ 0.57, 1.18 ]

Loprinzi 1999b 26/79 39/158 38.2 1.33 [ 0.88, 2.02 ]

Subtotal (95% CI) 178 336 100.0 1.15 [ 0.75, 1.76 ]

Total events: 63 (Megestrol acetate), 109 (Other drugs)



02 AIDS










Total (95% CI) 178 336 100.0 1.15 [ 0.75, 1.76 ]




0.1 0.2 0.5 1 2 5 10

Favours other drugs Favours treatment



Analysis 02.02. Comparison 02 Megestrol acetate vs other drugs (ITT), Outcome 02 Weight gain




Study Megestrol acetate Other drugs Weighted Mean Difference (Random) Weight Weighted Mean Difference (Random)


01 Cancer

Chen 1997 48 -1.71 (4.56) 41 -5.41 (3.19) 20.6 3.70 [ 2.08, 5.32 ]

Loprinzi 1999a 79 2.50 (4.45) 159 2.01 (3.24) 21.0 0.49 [ -0.61, 1.59 ]

Loprinzi 1999b 79 2.50 (4.45) 158 1.77 (2.58) 21.1 0.73 [ -0.33, 1.79 ]

Subtotal (95% CI) 206 358 62.7 1.53 [ -0.18, 3.25 ]



02 AIDS

Batterham 2001 4 10.20 (4.51) 6 4.01 (1.68) 16.2 6.19 [ 1.57, 10.81 ]

Timpone 1997 12 6.50 (1.10) 12 -2.00 (1.30) 21.1 8.50 [ 7.54, 9.46 ]

Subtotal (95% CI) 16 18 37.3 8.40 [ 7.46, 9.35 ]







Total (95% CI) 222 376 100.0 3.82 [ 0.06, 7.57 ]



-10 -5 0 5 10

Favours other drugs Favours M A



Analysis 02.03. Comparison 02 Megestrol acetate vs other drugs (ITT), Outcome 03 Weight gain





n/N n/N 95% CI (%) 95% CI

01 Cancer

Lai 1994 6/20 4/19 8.1 1.43 [ 0.48, 4.27 ]

Loprinzi 1999a 6/79 8/159 9.3 1.51 [ 0.54, 4.20 ]

Loprinzi 1999b 5/79 5/158 6.6 2.00 [ 0.60, 6.71 ]

Subtotal (95% CI) 178 336 24.0 1.60 [ 0.85, 3.03 ]




02 AIDS

Batterham 2001 4/4 5/6 76.0 1.20 [ 0.84, 1.72 ]

Subtotal (95% CI) 4 6 76.0 1.20 [ 0.84, 1.72 ]









Total (95% CI) 182 342 100.0 1.29 [ 0.94, 1.76 ]




0.1 0.2 0.5 1 2 5 10




Analysis 02.04. Comparison 02 Megestrol acetate vs other drugs (ITT), Outcome 04 Quality of life



Outcome: 04 Quality of life


n/N n/N 95% CI (%) 95% CI

01 Cancer

Lai 1994 7/20 5/19 9.8 1.33 [ 0.51, 3.48 ]

Loprinzi 1999a 22/79 45/159 48.1 0.98 [ 0.64, 1.52 ]

Loprinzi 1999b 21/79 37/158 42.1 1.14 [ 0.71, 1.80 ]

Subtotal (95% CI) 178 336 100.0 1.08 [ 0.80, 1.45 ]




02 AIDS










Total (95% CI) 178 336 100.0 1.08 [ 0.80, 1.45 ]




0.1 0.2 0.5 1 2 5 10




Analysis 03.01. Comparison 03 Sensitivity analysis, Outcome 01 Appetite improvement, treatment duration


Comparison: 03 Sensitivity analysis

Outcome: 01 Appetite improvement, treatment duration


n/N n/N 95% CI (%) 95% CI

01 treatment duration more than 6 weeks

Erkurt 2000 55/58 7/57 24.6 7.72 [ 3.85, 15.49 ]

Feliu 1992 30/76 8/74 24.4 3.65 [ 1.79, 7.44 ]

Loprinzi 1990b 24/67 16/66 27.1 1.48 [ 0.87, 2.52 ]

Schmoll 1992 37/63 6/28 23.9 2.74 [ 1.31, 5.74 ]

Total (95% CI) 264 225 100.0 3.21 [ 1.54, 6.70 ]




0.1 0.2 0.5 1 2 5 10

Favours placebo Favours MA

Analysis 03.02. Comparison 03 Sensitivity analysis, Outcome 02 Weight gain, treatment duration



Outcome: 02 Weight gain, treatment duration

Study Treatment Control Relative Risk (Random) Weight Relative Risk (Random)

n/N n/N 95% CI (%) 95% CI

01 Treatment duration more than 6 weeks

Feliu 1992 21/76 5/74 10.9 4.09 [ 1.63, 10.27 ]

Loprinzi 1990b 16/67 11/66 16.5 1.43 [ 0.72, 2.85 ]

Rowland 1996 26/122 8/121 14.7 3.22 [ 1.52, 6.83 ]

Schmoll 1992 17/63 4/28 9.7 1.89 [ 0.70, 5.10 ]

Tchekmedyian 1992 27/49 16/40 25.9 1.38 [ 0.87, 2.17 ]

Vadell 1998 38/99 13/51 22.3 1.51 [ 0.89, 2.56 ]

Total (95% CI) 476 380 100.0 1.86 [ 1.31, 2.63 ]

Total events: 145 (Treatment), 57 (Control)



0.1 0.2 0.5 1 2 5 10

Favours treatment Favours control



Analysis 03.03. Comparison 03 Sensitivity analysis, Outcome 03 Weight gain, treatment duration



Outcome: 03 Weight gain, treatment duration

Study Treatment Control Weighted Mean Difference (Random) Weight Weighted Mean Difference (Random)


01 Treatment duration more than 6 weeks

Chen 1997 48 -1.71 (4.56) 40 -3.99 (5.52) 25.2 2.28 [ 0.14, 4.42 ]

Erkurt 2000 58 5.00 (6.00) 57 -5.90 (7.00) 24.8 10.90 [ 8.52, 13.28 ]

Loprinzi 1990b 67 1.36 (4.99) 66 -0.22 (3.01) 26.2 1.58 [ 0.18, 2.98 ]

McQuellon 2002 28 -1.22 (6.25) 29 -4.80 (4.80) 23.8 3.58 [ 0.68, 6.48 ]

Total (95% CI) 201 192 100.0 4.54 [ 0.43, 8.66 ]



-10 -5 0 5 10

Favours Placebo Favours MA

Analysis 03.04. Comparison 03 Sensitivity analysis, Outcome 04 Appetite improvement, study quality



Outcome: 04 Appetite improvement, study quality

Study Megestrol acetate Control Relative Risk (Random) Weight Relative Risk (Random)

n/N n/N 95% CI (%) 95% CI

01 Study quality (Jadad score 3, 4 or 5)

Feliu 1992 30/76 8/74 17.0 3.65 [ 1.79, 7.44 ]

Loprinzi 1990b 24/67 16/66 19.9 1.48 [ 0.87, 2.52 ]

Subtotal (95% CI) 143 140 36.9 2.25 [ 0.92, 5.52 ]

Total events: 54 (Megestrol acetate), 24 (Control)



02 Study quality (Jadad score 2 or low)

Erkurt 2000 55/58 7/57 17.2 7.72 [ 3.85, 15.49 ]

Lai 1994 11/20 4/19 13.3 2.61 [ 1.00, 6.80 ]

Schmoll 1992 37/63 6/28 16.5 2.74 [ 1.31, 5.74 ]

Zeca 1995 13/16 5/17 16.0 2.76 [ 1.28, 5.99 ]

Subtotal (95% CI) 157 121 63.1 3.63 [ 2.06, 6.39 ]


0.1 0.2 0.5 1 2 5 10

Favours Control Favours MA (Continued . . . )



(. . . Continued)

Study Megestrol acetate Control Relative Risk (Random) Weight Relative Risk (Random)

n/N n/N 95% CI (%) 95% CI



Total (95% CI) 300 261 100.0 3.03 [ 1.83, 5.01 ]




0.1 0.2 0.5 1 2 5 10

Favours Control Favours MA

Analysis 03.05. Comparison 03 Sensitivity analysis, Outcome 05 Weight gain, study quality



Outcome: 05 Weight gain, study quality

Study Megestrol acetate Control Weighted Mean Difference (Random) Weight Weighted Mean Difference (Random)


01 Study quality (Jadad score 3,4 or 5)

De Conno 1998 21 1.06 (1.95) 21 -0.34 (1.01) 18.5 1.40 [ 0.46, 2.34 ]

Fietkau 1996 32 -0.80 (0.20) 32 -3.20 (3.20) 18.3 2.40 [ 1.29, 3.51 ]

Loprinzi 1990b 67 1.36 (4.99) 66 -0.22 (3.01) 17.7 1.58 [ 0.18, 2.98 ]

McQuellon 2002 28 -1.22 (6.25) 29 -4.80 (4.80) 14.1 3.58 [ 0.68, 6.48 ]

Subtotal (95% CI) 148 148 68.6 1.87 [ 1.20, 2.54 ]



02 Study quality (Jadad score o or low)

Chen 1997 48 -1.71 (4.56) 40 -3.99 (5.52) 16.0 2.28 [ 0.14, 4.42 ]

Erkurt 2000 58 5.00 (6.00) 57 -5.90 (7.00) 15.4 10.90 [ 8.52, 13.28 ]

Subtotal (95% CI) 106 97 31.4 6.57 [ -1.87, 15.02 ]



Total (95% CI) 254 245 100.0 3.53 [ 1.43, 5.62 ]



-10 -5 0 5 10

Favours control Favours MA



Analysis 03.06. Comparison 03 Sensitivity analysis, Outcome 06 Weight gain, study quality



Outcome: 06 Weight gain, study quality

Study Treatment Control Relative Risk (Random) Weight Relative Risk (Random)

n/N n/N 95% CI (%) 95% CI

01 Study quality (Jadad score 3,4 or 5)

Feliu 1992 21/76 5/74 9.5 4.09 [ 1.63, 10.27 ]

Loprinzi 1990b 16/67 11/66 15.2 1.43 [ 0.72, 2.85 ]

Tchekmedyian 1992 27/49 16/40 26.2 1.38 [ 0.87, 2.17 ]

Vadell 1998 38/99 13/51 21.8 1.51 [ 0.89, 2.56 ]

Subtotal (95% CI) 291 231 72.7 1.66 [ 1.13, 2.44 ]




02 Study quality (Jadad score 2 or low)

Lai 1994 6/20 3/19 5.7 1.90 [ 0.55, 6.54 ]

Rowland 1996 26/122 8/121 13.3 3.22 [ 1.52, 6.83 ]

Schmoll 1992 17/63 4/28 8.4 1.89 [ 0.70, 5.10 ]

Subtotal (95% CI) 205 168 27.3 2.49 [ 1.45, 4.27 ]




Total (95% CI) 496 399 100.0 1.83 [ 1.35, 2.50 ]




0.1 0.2 0.5 1 2 5 10

Favours treatment Favours control



Meg Acet in Anorexia

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