Sorafenib in combination with weekly topotecan in recurrent ovarian cancer, a phase I/II study of the Hoosier Oncology Group

ObjectiveThis trial determined the efficacy and tolerability of sorafenib and weekly topotecan in patients with platinum-resistant ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC).MethodsPrimary 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 400 mg and 800 mg orally daily. Topotecan dose was reduced from 4 mg/m2 to 3.5 mg/m2 IV weekly. The phase II regimen was sorafenib 400 mg daily and topotecan 3.5 mg/m2 weekly on days 1, 8, 15 of a 28 days cycle.Results16 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.ConclusionsThe 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.

► This phase I/II study determined efficacy and toxicity of the sorafenib and topotecan combination in platinum resistant ovarian cancer.
► Dose limiting toxicities were thrombocytopenia, neutropenia, rash; while myelosupression, fatigue, nausea, rash were most common toxicities during phase II.
► Efficacy was modest with only one partial response among 14 patients enrolled in the phase II trial.