Phase II study of irinotecan in combination with bevacizumab in recurrent ovarian cancer

Objectives

To evaluate the efficacy and safety of irinotecan and bevacizumab in recurrent ovarian cancer. The primary objective was to estimate the progression free survival (PFS) rate at 6 months. Secondary objectives included estimation of overall survival (OS), objective response rate (ORR), duration of response, and an evaluation of toxicity.

Methods

Recurrent ovarian cancer patients with no limit on prior treatments were eligible. Irinotecan 250 mg/m2 (amended to 175 mg/m2 after toxicity assessment in first 6 patients) and bevacizumab 15 mg/kg were administered every 3 weeks until progression or toxicity. Response was assessed by RECIST or CA-125 criteria every 2 cycles.

Results

Twenty nine patients enrolled (10 were platinum-sensitive and 19 were platinum-resistant). The median number of prior regimens was 5 (range 1–12); 13 patients had prior bevacizumab and 11 prior topotecan. The PFS rate at 6 months was 55.2% (95% CI: 40%–77%). The median number of study cycles given was 7 (range 1–34). Median PFS was 6.8 months (95% CI: 5.1–12.1 months); median OS was 15.4 months (95% CI: 11.9–20.4 months). In this study, no complete response (CR) was observed. The objective response rate (ORR; PR or CR) for all patients entered was 27.6% (95% CI: 12.7%–47.2%) and the clinical benefit rate (CR + PR + SD) was 72.4% (95% CI: 52.8%–87.3%); twelve patients experienced duration of response longer than 6 months. In the 24 patients with measurable disease, a partial response (PR) was documented in 8 (30%) patients; 13 patients maintained stable disease (SD) at first assessment. The most common grade 3/4 toxicity was diarrhea. No treatment-related deaths were observed.

Conclusions

Irinotecan and bevacizumab has activity in heavily pre-treated patients with recurrent ovarian cancer, including those with prior bevacizumab and topoisomerase inhibitor use.