Adjuvant therapy: LMS High activity of gemcitabine/docetaxel in advance disease suggests potential role as adjuvant therapy Adjuvant phase II study of dose-rated based gemcitabine/docetaxel followed by doxorubicin Endpoints: –DFS at year 2 If DFS at year 2 is promising, would propose RCT

Study/author RecurrenceN/StagesPFSComments Ifos 4.5 gm5/64—I/II 2—III/IV 65% at 1 Y 30% at 2 Y Retrospective GOG: Dox 60/m2 x 8 v. observe Obs 61% (14/23) Dox 44% (11/25) Stage I/II (no data on grade, mitotic rate) 62% at 2 Y (MMT and LMS) Prior RT allowed, no diff in Rec Rate Gaducci (Gyn Onc 1996) No chemo 25/64 (39%) Chemo 4/9 (44%) I, II60% at 2 YPFS by mitotic rate % % >20 20% GOG retrospective (Cancer 1993) 59 (83% stage I, 17% II) 29% at 3 YPFS by mitotic rate <10 100% % >20 20% Pelvic 1 st 14%

Schema Gem 900 d 1, 8 + doce 75 d 8; q 3 wk x 4 cycles Repeat CT scan Doxorubicin 60 mg/m2 q 3 w x 4 Repeat CT scan 6 weeks after CT c/a/p every 3 mo for 2 y, then every 6 mo

Objectives PRIMARY: -two-year PFS (target > 50% PFS at 2 years) SECONDARY: -safety, tolerability as adjuvant therapy -explore impact of age, “STS stage”, mitotic rate, ER and PR, menopausal status on PFS

Should we stage like STS? FIGO stage I and II -Indifferent to size, grade, depth High grade LMS -would be STS stage IIB or III

STS v. FIGO staging FIGO I (uterus) or II (uterus and cervix) grade 2, 3, or 4 T1b or T2b By definition all uterine sarcs are “deep” Explore whether STS staging is superior to FIGO in terms of ability to predict PFS

Statistical approach Target accrual 45 patients Bayesian model for continuous assessment of PFS and safety Accrue at least 15 patients per year Stop early if data suggest 2 year PFS will be no better that 30%

Data management On line SARC registration On line data entry Data monitored by SARC Real-time assessment of endpoints by statistical office

Milestones Full protocol written, reviewed, approved by SARC, industry sponsors, MSKCC IRB Contracts between SARC and Lilly, SARC and Sanofi-Aventis are completed Gemcitabine and docetaxel both supplied Drug distribution from SARC to institutions