A phase II, open-label, non-randomized, prospective study assessing paclitaxel, carboplatin and metformin in the treatment of advanced stage ovarian carcinoma.

OBJECTIVE: The purpose of this study was to assess the efficacy and tolerability of a paclitaxel, carboplatin and metformin regimen in the first-line treatment of advanced-stage ovarian, fallopian tube, and primary peritoneal carcinoma. METHODS: Eligible subjects underwent surgery and 6 cycles of neoadjuvant or adjuvant dose-dense intravenous paclitaxel (80 mg/m²), carboplatin (area under the curve 5 or 6 on Day 1), and oral metformin (850 mg daily). Study participants who completed their primary therapy and attained a clinically defined complete or partial response (PR) were treated with a planned 12 cycles of paclitaxel (135 mg/m² every 21 days) and metformin (850 mg twice daily) maintenance therapy. RESULTS: Thirty subjects received a median of 6 cycles (range, 5-6) of primary induction chemotherapy and were eligible for response evaluation; twenty-three patients exhibited a complete response, while 3 study patients obtained a PR (an overall response rate of 86.7%). Grade 3-4 hematological toxicity included neutropenia (43.3%), thrombocytopenia (10%) and anemia (36.7%). There was no incidence of grade 3-4 neuropathy although 15 patients (50%) developed grade ≤2 neurotoxicity. Additionally, we observed grade ≤2 diarrhea in 20 (66.7%) subjects. The median progression-free survival was 21 months (range, 3-52) and overall median survival was 35 months (range, 15-61). The subjects also received an aggregate 103 cycles (median, 12; range, 6-12) of maintenance chemotherapy. CONCLUSION: The study results suggest that the combination of paclitaxel, carboplatin and metformin is associated with moderate efficacy and a reasonable toxicity profile.