CORRESPONDENCE

Dr. Bhargava has received honorarium for partic-ipating in an advisory board meeting for Sanofi-Synthelabo US, the manufacturer of oxaliplatin.

Hypersensitivity and Idiosyncratic Reactionsto Oxaliplatin

In their review of hypersensitivity and idiosyncratic reactions tooxaliplatin, Thomas et al.1 concluded that patients who develop

severe hypersensitivity reactions (HSRs) to oxaliplatin are unlikelyto tolerate further therapy. We wish to report a desensitizationprotocol developed at our institution that allowed successful re-treatment of a patient who had experienced a severe HSR tooxaliplatin.

A 50-year-old female with metastatic colon carcinoma hadpreviously received 12 courses of oxaliplatin on a clinical trialwithout any allergic reactions. Although her tumor was respondingto oxaliplatin-based chemotherapy, she had to be removed fromthe study because of persistent neutropenia. Subsequent treat-ments for her tumor proved ineffective. Approximately 18 monthslater, oxaliplatin became commercially available in the U.S. and wedecided to reinstitute treatment with this agent. The patient begantreatment with a combination of oxaliplatin and capecitabine andtolerated her first cycle well. Approximately 15 minutes after hersecond infusion of oxaliplatin, the patient reported palpitationsand flushing and was found to be hypotensive (blood pressurereading of 70/40 mm Hg) with mild pulmonary wheezing. Theoxaliplatin infusion was immediately withdrawn and she wastreated with intravenous (i.v.) fluids, diphenhydramine at a dose of50 mg i.v., and hydrocortisone at a dose of 100 mg i.v.. The patientalso developed a diffuse macular rash over her body and rigors thatwere treated with meperidine at a dose of 25 mg i.v.. Her symptomsresolved within 90 minutes. For her next cycle of treatment, thepatient was premedicated with oral dexamethasone beginning 24hours prior to chemotherapy and she also received i.v. dexameth-asone and diphenhydramine 30 minutes prior to treatment. Inaddition, the rate of infusion of oxaliplatin was reduced by 50%.Despite these measures, the patient experienced a similar HSRapproximately 20 minutes after the oxaliplatin infusion was initi-ated.

Because the patient wanted to continue treatment with oxalipla-tin, we devised a 4-hour desensitization protocol adapted from aprevious report for anaphylaxis to carboplatin.2 Four serial dilutionsof oxaliplatin were prepared based on the calculated total dose(1:10,000, 1:1000, 1:100, and 1:10), each in 100 mL of D5W. Startingwith the lowest dilution, each bag of oxaliplatin was infused over 1hour with careful monitoring of vital signs. The patient tolerated thedesensitization well and the remainder of her dose was infused over2 hours. During infusion of the final dose, she developed a faintmacular rash with itching over her lower extremities, which re-sponded to i.v. hydrocortisone. For her subsequent treatments, thelength of the final infusion of oxaliplatin was prolonged to 4 hoursand she was premedicated with hydrocortisone at a dose of 100 mg

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i.v. prior to her desensitization, which resulted in nofurther reactions. The patient was able to tolerate sixcycles of treatment with the desensitization regimen.Her tumor regressed after three cycles but unfortu-nately grew back after six cycles of therapy, leading todiscontinuation of treatment.

Treatment options for metastatic colorectal car-cinoma are limited, and oxaliplatin is a useful agentin the treatment of this disease. In clinical trials withcolorectal carcinoma patients, 10% of patients ex-perienced allergic reactions to combination chemo-therapy with oxaliplatin.3 In all cases of a severeHSR, treatment had to be discontinued.4,5 To theour knowledge, this is the first report of successfuldesensitization after a severe HSR to oxaliplatin.This desensitization regimen may allow physiciansto continue treatment with oxaliplatin in patientswho have experienced a severe HSR and have ex-hausted other treatment options for colorectal car-cinoma.

REFERENCES1. Thomas RR, Quinn MG, Schuler B, Grem JL. Hypersensitiv-

ity and idiosyncratic reactions to oxaliplatin [review]. Can-cer. 2003;97:2301–2307.

2. Windom HH, McGuire WP, Hamilton RG, Adkinson NF.Anaphylaxis to carboplatin- a new platinum chemothera-peutic agent. J Allergy Clin Immunol 1992;90:681– 683.

3. Sanofi-Synthelabo US. Oxaliplatin–manufacturer’s packageinsert. New York: Sanofi-Synthelabo US, 2003. Availablefrom URL: www.eloxatin.com [accessed 28 July 2003].

4. Tournigand C, Maindrault-Goebel F, Louvet C, et al. Severeanaphylactic reactions to oxaliplatin. Eur J Cancer. 1998;34:1297–1298.

5. Medioni J, Coulon MA, Morere JF, et al. Anaphylaxis afteroxaliplatin [letter]. Ann Oncol. 1999;10:610.

Pankaj Bhargava, M.D.David Gammon, R.Ph.

Division of Hematology/OncologyUniversity of Massachusetts Medical School

UMass Memorial Medical CenterWorcester, Massachusetts

Michael J. McCormick, M.D.

Division of Pulmonary, Allergyand Critical Care Medicine

University of Massachusetts Medical SchoolUMass Memorial Medical Center

Worcester, MassachusettsDOI 10.1002/cncr.11901

Second Neoplasms FollowingMegavoltage Radiationfor Pediatric Tumors

We recently published a report on the developmentof second neoplasms after the treatment of child-

hood malignancies with radiotherapy.1 Second neo-plasms were observed in 8.3% of patients, at a medianof 15.5 years after radiotherapy. We now wish to ana-lyze the incidence of neoplasms after the treatment ofbenign childhood tumors with radiotherapy, whichwas not considered in our recent report.

We reviewed the medical records of 39 patientswho were age 17 years or younger (median age, 5.2years) at the time of treatment with megavoltageradiation for benign disease; who were treated be-tween December 6, 1957, and April 1, 1980, at theUniversity of Minnesota Hospitals (Minneapolis,Minnesota); and who survived for at least 5 yearsafter radiotherapy. The benign conditions treatedincluded Langerhans cell histiocytosis (n � 23), an-eurysmal bone cysts (n � 6), pituitary adenoma (n� 4), hemangioma (n � 3), angiofibroma (n � 2),and lymphoid hyperplasia (n � 1). Follow-up infor-mation was acquired as described previously,1 witha median follow-up period of 26.7 years. The stan-dardized incidence ratio (i.e., the ratio of observedcases of neoplasms to expected cases) was calcu-lated as described previously.1

Three of 39 patients (7.7%) had developed asubsequent neoplasm at last follow-up. The firstpatient, age 13 years at the time of treatment for anangiofibroma, developed squamous cell carcinomaof the nasopharynx within the radiation treatmentfield 33 years later. The second patient, age 10months at the time of treatment for Langerhans cellhistiocytosis, developed an ependymoma within theoriginal radiation treatment field 15 years later. Thethird patient, age 4 months at the time of treatmentfor Langerhans cell histiocytosis, developed acutemyelogenous leukemia 9 years later; it is noteworthythat this patient also was treated with etoposide,chlorambucil, and cyclophosphamide, which havebeen associated with the subsequent developmentof acute leukemias.2 The standardized incidence ra-tio for development of a subsequent neoplasm inthe current cohort was 5.10 (95% confidence interval[CI], 1.03–14.27).

In our recent report,1 the standardized inci-dence ratio for development of a second neoplasmfollowing the treatment of childhood malignancieswith radiotherapy was 5.2 (95% CI, 3.4 –7.6), similar

212 CANCER January 1, 2004 / Volume 100 / Number 1

to the standardized incidence ratio in the currentreport (5.10). Both of the patient groups studieddeserve increased surveillance (e.g., early mammo-grams, thorough examinations of previously irradi-ated areas) with respect to the development ofsubsequent neoplasms and active counseling re-garding behaviors that can be modified (e.g., sunexposure, smoking) to reduce the risk of secondmalignancies.

REFERENCES1. Gold DG, Neglia JP, Dusenbery KE. Second neoplasms fol-

lowing megavoltage radiation for pediatric tumors. Cancer.2003;97:2588 –2596.

2. Karp J, Sarkodee-Adoo C. Therapy-related acute leukemia.Clin Lab Med. 2000;20:71– 81.

Douglas G. Gold, M.D., Ph.D.Department of Radiation Therapy

University of Minnesota Medical SchoolMinneapolis, Minnesota

Joseph P. Neglia, M.D., M.P.H.Department of Pediatrics

University of Minnesota Medical SchoolMinneapolis, Minnesota

Roger A. Potish, M.D.Kathryn E. Dusenbery, M.D.

Department of Therapeutic RadiologyUniversity of Minnesota Medical School

Minneapolis, MinnesotaDOI 10.1002/cncr.11870

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