Phase I/II study of a docetaxel (DOC) and gemcitabine (GEM) combination for early recurrent (≤12 months)(ER) or refractory (R) epithelial ovarian cancer (EOC): Kansai Clinical Oncology Group, Japan

Abstract

5046 Background:There is no standard chemotherapy regimen for EOC that does not respond to platinum-based chemotherapy (R-EOC), or responds but progresses within 12 months after completing chemotherapy (ER-EOC). Purpose: To determine the efficacy of a DOC and GEM combination for R-EOC or ER-EOC, we conducted phase 1/2 study. Methods:Between October 2000 and November 2003, R-EOC or ER-EOC patients (pts) entered this multi-institutional study. Eligible criteria: histologically verified EOC, age 16 -75 years, ECOG-PS ≤2, adequate bone marrow, hepatic, and renal function, and written informed consent. GEM was administered on days 1 and 8, and DOC on day 8. This treatment was repeated every 3 weeks. The doses were escalated as follows: dose level 1 (DL1); DOC 70 mg/m2, GEM 800 mg/m2, DL2: DOC 70 mg/m2, GEM 1000 mg/m2. Toxicities were assessed according to NCI-CTC ver2.0J and responses were assessed according to both RECIST for measurable disease and Rustin's criteria for CA125. Results:Thirty-four pts were enrolled and administered 95 cycles. The median cycle was 3 (1–7 cycles), median age was 56 years (21 to 74 years), and median interval from prior chemotherapy was 2 months (1 to 12 months). Seventeen pts received more than 3 chemotherapy regimens before the enrollment. Three pts experienced no dose-limiting toxicities (DLTs) in DL1. Two of the three pts in DL2 were experienced DLTs: febrile neutropenia grade 3 (1), and thrombocytopenia grade 4 (1). Then, 28 patients were subjected to the phase 2 study with DL1 as a recommended dose. Thirty-two patients were assessable for response. Response rate was 19.1% (6/32) with 1CR (3.1%), 5PR (16%), and 9SD(28%). One-year and 2-year survival were 51.2% and 23.4%, respectively. The median survival time was 13 months. Toxicities were mainly hematological (G3/G4): neutropenia (16%/50%), thrombocytopenia (19%/0%), anemia (13%/0%), and febrile neutropenia (3%/0%). There were no grade 3 or 4 non-hematological toxicities. Conclusions:A DOC and GEM combination for R-EOC and ER-EOC with DL1 is active and well tolerable. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Japan K.K.