Feasibility of Interval Cytoreduction Following Neoadjuvant Chemotherapy With Carboplatin, Weekly Paclitaxel, and Bevacizumab for Advanced Ovarian Cancer—A Phase 1 Study. Issue 4 (1st May 2014)

• Record Type: Journal Article
• Authors: Salani, Ritu; O'Malley, David M.; Copeland, Larry J.; Cohn, David E.; Backes, Floor J.; Fowler, Jeffrey M.; Eisenhauer, Eric L.
• Is Part Of: International journal of gynecological cancer. Volume 24:Issue 4(2014)
• Page Start: 682
• Page End: 686
• Publication Date: 2014-05-01
• Subjects: Neoadjuvant chemotherapy -- Ovarian cancer -- Bevacizumab -- Interval cytoreductive surgery; Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1097/IGC.0000000000000107
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : Objective: The 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). Methods: Using 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/m 2 ) 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. Results: Nine patients were enrolled with a median age of 64 years. There were no dose-limiting toxicities, and weekly paclitaxel 80 mg/m 2 was 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. Conclusions: A 4-cycle neoadjuvant regimen of carboplatin area under the curve of 5, weekly paclitaxel 80 mg/m 2, 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.