Clique para editar o título mestre. Are there benefits from chemotherapy to early endometrial...
-
Upload
cecil-craig -
Category
Documents
-
view
213 -
download
0
Transcript of Clique para editar o título mestre. Are there benefits from chemotherapy to early endometrial...
Clique para editar o título mestre
Are there benefits from chemotherapy to early endometrial cancer?
Ursula Matulonis, M.D.Associate Professor of Medicine, Harvard Medical SchoolDirector/Program Leader, Medical Gynecologic Oncology
Dana-Farber Cancer InstituteBoston MA
Email: [email protected]
Risk categories for recurrence
• Low Risk•no poor prognostic features
• Intermediate Risk•deep myometrial invasion•presence of lymphovascular invasion•high grade or rare tumor histology
• High Risk•positive nodes•extrauterine disease
Creasman WT, et al. AJ Obstet Gynecol 1999;181:31-34.
Type I vs. Type II endometrial cancer
Type I: Endometrioid--Unopposed estrogen (hyperplasia)
-- Low to moderate grade, minimal myometrial invasion
-- Good prognosis
Type II: Serous--Lack of unopposed
estrogen (atrophy)-- High grade, often with
metastases--Poorer prognosis (more
rare but causes a disproportionate number of deaths)
NCCN guidelines for surgically staged stage I cancer
+/- adverse factors
Grade 1 Grade 2 Grade 3
Stage IA (<50% myometrial invasion)
Adverse risk factors not present
observe Observe or brachy
Observe or brachy
Adverse risk factors present
obs or brachy Obs or brachy +/- pelvic RT
Obs or brachy +/- pelvic RT
Stage IB (≥ 50% myometrial invasion)
Adverse risk factors not present
obs or brachy Observe or brachy
Obs or brachy +/- pelvic RT
Adverse factors present
Obs or brachy +/- pelvic RT
Obs or brachy +/- pelvic RT
Obs or pelvic RT and/or brachy +/- chemotherapy (cat 2B for chemotherapy)
Adverse risk features: age, +LVI, tumor size, lower uterine
(cervical/gland involvement)www.nccn.org
Grade 1 Grade 2 Grade 3
All Stage II
Vag Brachy +/- pelvic RT Pelvic RT + vaginal brachy
Pelvic RT + vag brachy +/- chemotherapy (category 2B)
Stage IIIA
Chemotherapy +/-RT or involved field RT +/- chemotherapy or pelvic RT +/- brachy
Chemotherapy +/-RT or involved field RT +/- chemotherapy or pelvic RT +/- brachy
Chemotherapy +/-RT or
involved field RT +/- chemotherapy or pelvic RT +/- brachy
NCCN guidelines for stage II and IIIAIIIA: Tumor invades the serosa of the uterus and/or adnexae
www.nccn.org
Is +Peritoneal cytology an independent risk factor? In the absence of adverse pathological features (high grade tumors, deep invasion, serous orclear cell path or extrauterine disease spread), + cytology is not generally treated.
Is intraluminal fallopian tube spread considered stage III?
Surgically staged Stage IIIB or higher
Stage Treatment
Stage IIIB Chemotherapy +/- RT
Stage IIIC1 (+ pelvic nodes)
Chemotherapy +/- RT
Stage IIIC2 (+para-aortic nodes)
Chemotherapy +/- RT
Stage IVA, IVB (no gross residual cancer)
Chemotherapy +/- RT
www.nccn.org
Addition of chemotherapy to RT versus RT alone
Results of 2 pooled studies:NSGO-EC-9501/EORTC-55991
(Nordic study) and MaNGO ILIADE-III
540 patients enrolled; 534 evaluable.
Eur J of Cancer 46:2422, 2010
NSGO-EC-9501/EORTC-55991 and MaNGO ILIADE-III (pooled data)
**Nordic trial showed that addition of CT to RT was associated with a significant 36% reduction in the risk of relapse or death and a sig 49% reduction in the risk of death from endometrial cancer; MaNGO trial showed same direction but not significant.
Eur J of Cancer 46:2422, 2010
Problems with these studies
Nordic trial- study closed early because of poor accrual- chemotherapy could be given either before or after RT- RT is lower than standard of care (44Gy)- serous and clear cell cancers were allowed. - no standard chemotherapy regimen prescribed.
MaNGO trial- higher staged cancers included- serous and clear cell excluded
Other problems: pooled data of different stages, histologies, treatments.
Eur J of Cancer 46:2422, 2010
Endometrial cancer: GOG 122 for advanced III/IV cancer
Phase III study: GOG 122
Doxorubicin 60 mg/m2Cisplatin 50 mg/m2
every 3 weeks x 8 cycles
WART (AP/PA)30 Gy x 20 = 150 Gy15 Gy boost to pelvic +/- PA
Primary endpoint: PFSSecondary endpoint: OSMedian F/u: 60 months- 73% were stage III
Maximum Doxorubicin total dose = 420 mg/m2
Randall et al, JCO 2006
Progression-free survival improved with chemotherapy: GOG 122
J Clin Oncol; 24:36-44 2006
HR 0.71 (95% CI, 0.55 to 0.91; P = .007)
Survival better with chemotherapy:GOG 122
J Clin Oncol; 24:36-44 2006
HR 0.68 (0.52-0.89; p<0.01)
Survival by treatment and stage
Randall, M. E. et al. J Clin Oncol; 24:36-44 2006
Ongoing studies of adjuvant therapy for endometrial cancer
Danish study, n=678 (AGO, EORTC, MaNGO, and others)
Stage I and II endometrial cancer treated with surgery. Phase III study, n = 678
Eligibility:Stage I grade 3 endometrioid adenocarcinomaStage II endometrioid adenocarcinomaStage I and II type 2 histology (clear cell, serous, squamous cell carcinoma, or undifferentiated carcinoma)
Randomized to:1) observation2) 6 cycles of carboplatin and paclitaxel.
NCT01244789
GOG 249: Phase III
Endometrial cancer1) stage I with high-intermediaterisks with +/- cytology2) stage II (any histology), +/- risk factors3) stage I/II serous or clear cellcancers with neg cytologyn= 562
Pelvic RT optional vaginal cuff boost
Vaginal cuff brachy +3 cycles of paclitaxel 175 mg/m2 +carboplatin AUC 6
High-intermediate risks:age ≥ 70 yrs with one risk factorage ≥ 50 yrs with 2 risk factorsage ≥ 18 yrs with 3 risk factors
Risk factors:grade 2 or 3 tumor+LVI outer ½ myometrial invasion
NCT00807768
NCT00411138
Clique para editar o título mestre
GOG 258
Endometrial cancerstage I-IV
Paclitaxel 175 mg/m2Carboplatin AUC 6q21 days x 6 cycles
Volume directed RT +cisplatin 50 mg/m2 days 1, 28followed by:Paclitaxel 175 mg/m2Carboplatin AUC 5q21 days x 4 cyclesOpened: 6/29/09
Phase IIIN=804
GOG 258
NCT00942357
Incorporation of bevacizumab into early stage endometrial cancer treatment
No extrauterinedisease outsideof the pelvis
NCT01005329
Conclusions
• When does our group use adjuvant chemotherapy for endometrial cancer and What type of chemotherapy?
1) Use IV carboplatin and paclitaxel2) Sequential therapy3) Clinical situations: Stage III or higher regardless of histology, Type II tumors (serous, clear cell) (any stage)Uterine carcinosarcomasAs part of a clinical trial
Follow the NCCN guidelines