A phase II trial of Sunitinib malate in recurrent and refractory ovarian, fallopian tube and peritoneal carcinoma

ObjectiveOvarian cancer is a highly angiogenic tumor and a model for antiangiogenic research. The tyrosine kinase receptor inhibitors target several receptors allowing for the pharmacological disruption of several independent pathways. Sunitinib malate® is a multitargeted tyrosine kinase inhibitor. A phase II study utilizing a modified dosing schedule was conducted to assess the efficacy and safety of Sunitinib® in recurrent ovarian, fallopian tube and peritoneal carcinoma.MethodsA nonrandomized phase II study was modeled as a two-stage Simon design initially enrolling 17 evaluable participants in stage one and 18 patients in stage two. Patients received the study drug at 37.5 mg every day over a 28 day treatment cycle until clinical or radiological evidence of progressive disease. Disease was evaluated radiographically and best overall response was defined using the RECIST 1.0 criteria. The primary objective of this study was to define the response rate (defined as complete response and partial response) while the secondary objectives included both the progression free rate as well as the safety of this agent in this patient population.ResultsThe response rate (PR + CR) was 8.3% (95% confidence interval: 1.8%, 22.5%). The 16-week and 24 week progression-free survival estimate was 36% (95% confidence interval and 19.2%), respectively. The median progression-free survival estimate was 9.9 weeks. Hypertension and gastrointestional events were the most common toxicities noted.ConclusionsA modest response rate of 8.3% was achieved with Sunitinib malate®. This phase II study adds to the body of literature of VEGFR inhibitors and further underscores the need of defining a genetic angiogenic signature.

► Sunitinib achieved a modest response rate of 8.3 % in ovarian cancer patients.
► Grade 1/2 toxicity with tyrosine kinase inhibitors can have significant consequences.
► Response to Sunitinib can be seen even following previous antiangiogenic therapy but further dedicated and prospective studies are needed to address this concept.