ABSTRACT
OBJECTIVE: This trial determined the efficacy and tolerability of sorafenib and weekly topotecan in patients with platinum-resistant ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC). METHODS: Primary endpoints were maximum tolerated dose of sorafenib with weekly topotecan (phase I) and response rate (phase II). Secondary endpoints were progression free survival (PFS), overall survival (OS), toxicity, and rate of clinical benefit. Eligibility included recurrent platinum-resistant OC or PPC, <3 prior regimens, normal end-organ function. 3+3 dose escalation was used for phase I, sorafenib being tested at 400mg and 800 mg orally daily. Topotecan dose was reduced from 4 mg/m(2) to 3.5mg/m(2) IV weekly. The phase II regimen was sorafenib 400mg daily and topotecan 3.5mg/m(2) weekly on days 1, 8, 15 of a 28 days cycle. RESULTS: 16 patients were enrolled in phase I and 14 patients in phase II. Median age was 52.5 years (range 35-79), 27 patients had OC, and 3 PPC. Median number of cycles administered was 2.5 (0-15). There were 5 partial responses (PR) (16.7%), and 14 patients (46.7%) with stable disease (SD). Four PRs were recorded during phase I and 1 during phase II. One of those PRs occurred in a patient with platinum-sensitive disease. Grade 3/4 toxicities included leukopenia/neutropenia (23%), thrombocytopenia (17%), anemia (10%), fatigue, nausea, vomiting (7% each). One case of grade 3 hand-foot syndrome was recorded. CONCLUSIONS: The combination of sorafenib and topotecan causes significant toxicity, precluding administration of full doses and resulting in modest clinical efficacy in platinum resistant OC or PPC.