Phase II study of adjuvant gemcitabine plus docetaxel (GD) for completely resected stage I-IV high grade uterine leiomyosarcoma (HGuLMS)

Abstract

5591 Background: Patients (pts) with completely resected stage I-IV HGuLMS are at high risk for recurrence, with reported 2-year progression-free survival ranging from 19–30% (Dinh, Gyn Onc 2004; Major, Cancer 1993). No adjuvant treatment has been shown to improve survival, although prospective data are limited. GD achieves objective responses in metastatic uLMS. We sought to determine whether 4 cycles GD given after complete resection of stage I-IV HGuLMS would yield a 2-year PFS of at least 40%, in order to determine whether GD was worth pursuing as an adjuvant strategy in a randomized trial. Methods: Eligible pts with completely resected HGuLMS within 8 weeks of surgery, no prior GD, no evidence of disease on post-resection CT, KPS = 80, and adequate organ function were treated with G 900 mg/m2 over 90 minutes days 1 and 8 + D 75 mg/m2 d8, with GCSF or pegfilgrastim, every 3 weeks for 4 cycles. CT was performed at baseline, after cycle 4, and every 3 months. Progression defined as new evidence of disease on CT. Results: 25 pts (median age 49, range 37–73) enrolled; 23 evaluable (1-never treated, 1-ineligible). Grade 3 related toxicities were: neutropenia (2/23) 8.7%, febrile neutropenia (2/23) 8.7%, anemia (2/23) 8.7%, thrombocytopenia (1/23) 4.3%, diarrhea (1/23) 4.3%, hyperglycemia (2/23) 8.7%, pulmonary (2/23) 8.7%; there were no ≥ grade 4 toxicities. With median follow-up of 29 months (range 0.5 to 45 months) for all pts, PFS at 2 y and 3 y is 45%, and median OS is not yet reached. For the 18 pts with stage I or II uLMS 2-y and 3-y PFS is 58%, and median PFS is 38 months (95%C.I. 6 months to not yet reached). Sites of first recurrence were: lung only-3/23 (13%); pelvis only-5/23 (22%); both-5 (22%). Treatment of recurrence was at physician discretion and included resection, resection plus pelvic radiation, and/or chemotherapy. Conclusions: Pts treated with post-resection GD for stage I-IV HGuLMS had 2-y and 3-y PFS that appears superior to historical rates of PFS. Incorporation of GD into a randomized trial of adjuvant chemotherapy vs adjuvant pelvic radiation for resected stage I and II uLMS is planned. No significant financial relationships to disclose.