CA-125 response as a marker of clinical benefit in patients with recurrent ovarian cancer treated with gemcitabine and sorafenib—A trial of the PMH Phase II Consortium
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5519 Background: Molecularly targeted agents are expected to have a cytostatic effect on cancers, thus traditional radiographic criteria for objective response may not be optimal in evaluating these agents. There is considerable preclinical rationale for the use of angiogenesis inhibitors in ovarian cancer (OC), and early phase trials of these agents have suggested activity. We have completed a phase II trial evaluating the efficacy of the combination of gemcitabine (GEM), a cytotoxic agent with activity in OC, and sorafenib (SOR), a novel mutitargeted kinase inhibitor with antiangiogenic activity, in patients (pts) with recurrent OC. Methods: Eligible pts had recurrent OC after platinum-based therapy and received up to 2 prior lines of chemotherapy for recurrence. All pts were gemcitabine-naive. GEM (1,000 mg/m2 i.v.) was given weekly for 7 weeks out of 8 weeks in the first cycle, then weekly for the first 3 weeks of each subsequent 4-week cycle. SOR (400 mg p.o. bid) was given continuously. The primary endpoint was objective response rate by RECIST criteria. Secondary endpoints included CA-125 response, time to progression (TTP), overall survival (OS) and toxicity. Results: 43 pts were accrued to this study. 137 (median 3; range: 1–19) cycles of treatment were given to 38 evaluable pts. 26 were evaluable for CA-125 response. Median age was 60 (range: 37–78). 44% of pts were ECOG PS 0 and 56% were PS 1. Using RECIST criteria, 2 pts (4.7%) had a confirmed partial response and 26 pts (60.4%) had a best response of stable disease. 9/26 pts (36.6%) with abnormal baseline CA-125 level achieved a CA-125 response using GCIG criteria. The median TTP was 5.4 months (95% CI: 3.5–9.5) and the median OS was 13.3 months (95% CI: 9.0-NR). The most frequent grade 3 or 4 adverse events were lymphopenia (32%), neutropenia (21%), thrombocytopenia (21%), hand-foot syndrome (21%), fatigue (16%), and hypokalemia (16%). Conclusions: The combination of GEM and SOR is well tolerated and associated with encouraging rates of disease stability. This trial illustrates the need for novel clinical trial design and response endpoints in order to more clearly identify the activity of targeted therapies in recurrent OC. No significant financial relationships to disclose.
