Feasibility of Interval Cytoreduction Following Neoadjuvant Chemotherapy With Carboplatin, Weekly Paclitaxel, and Bevacizumab for Advanced Ovarian Cancer—A Phase 1 Study

Abstract

ObjectiveThe objective of this study was to determine a dosing schedule of neoadjuvant chemotherapy using carboplatin, paclitaxel, and bevacizumab in women with advanced ovarian cancer, evaluating feasibility and outcomes from interval cytoreductive surgery (ICS).MethodsUsing a “3+3” design, eligible patients received carboplatin (area under the curve, 5) and bevacizumab (15 mg/kg) every 3 weeks with escalating doses of weekly paclitaxel (60, 70, and 80 mg/m2) for 3 cycles. Patients then received 1 cycle of chemotherapy without bevacizumab followed by ICS. The primary objective was to determine a feasible dosing schedule. Secondary objectives included defining toxicity, response rates based on imaging, and surgical outcomes defined by residual disease following ICS and 30-day postoperative outcomes.ResultsNine patients were enrolled with a median age of 64 years. There were no dose-limiting toxicities, and weekly paclitaxel 80 mg/m2was deemed feasible. During chemotherapy treatment, there were a total of 7 attributable grade 3 toxicities, which most commonly included neutropenia and thromboembolism. All patients demonstrated a response on imaging before surgery, with a median reduction in disease of 56.4% (range, 36.9%–100%). Optimal ICS was performed in all patients, and 78% had no gross residual tumor. There were no intraoperative complications; however, 1 patient experienced an anastomotic leak (grade 4) 10 days after surgery requiring repeat operation.ConclusionsA 4-cycle neoadjuvant regimen of carboplatin area under the curve of 5, weekly paclitaxel 80 mg/m2, and bevacizumab 15 mg/kg for cycles 1 to 3, followed by interval cytoreduction, was feasible. Optimal ICS was achieved in all patients, and surgery was associated with acceptable morbidity.