Increased incidence of severe gastrointestinal events with first-line paclitaxel, carboplatin, and vorinostat chemotherapy for advanced-stage epithelial ovarian, primary peritoneal, and fallopian tube cancer

Abstract

Objectives: We sought to assess the response rate and toxicity of paclitaxel, carboplatin, and vorinostat primary induction therapy for the treatment of advanced-stage ovarian carcinoma. Methods: Patients were treated with 6 cycles of weekly paclitaxel (80 mg/m2), carboplatin (6 times area under the curve), and vorinostat (200 mg) every 28 days according to an institutional review boardYapproved protocol. The subjects were eligible for response evaluation; in patients who achieved stable disease or better following the conclusion of primary induction chemotherapy, they were subsequently treated with a planned 12 cycles of paclitaxel (135 mg/m2) and vorinostat (400 mg) maintenance chemotherapy every 28 days. Results: Eighteen patients received a combined 90 cycles (median, 6 cycles; range, 1Y6cycles) of primary induction chemotherapy. Of the 18 subjects, 7 demonstrated a complete response, and 2 subjects exhibited a partial response (a total response rate of 50.0%). Eight patients also received a combined total of 50 cycles (median, 5 cycles; range, 1Y12 cycles) of consolidation therapy. Grade 3/4 neutropenia and thrombocytopenia were observed in 9 (56.3%) and 2 (12.5%) patients. One patient (6.3%) developed grade 3 anemia, and another (6.3%) manifested a grade 3 neuropathy. Remarkably, we observed a significant gastrointestinal event (eg, bowel anastomotic perforation) in 3 patients, which effectuated the study's closure. Conclusions: Because the current study was prematurely terminated, we cannot derive a conclusive assessment regarding the efficacy of this treatment. Nevertheless, the high incidence of severe gastrointestinal toxicity warrants further consideration when using vorinostat in the adjuvant setting for patientswho have undergone a bowel resection as part of their initial tumor debulking. © 2013 by IGCS and ESGO.