Abstract

BackgroundThe addition of bevacizumab to standard chemotherapy prolongs progression free survival in the first line treatment of epithelial ovarian cancer (EOC), but its cost/effectiveness is debated. We assessed the safety and activity of a lower dose of bevacizumab in pretreated advanced stage EOC.MethodsWe treated 15 patients, mostly with platinum resistant EOC, who had received a median of four prior cytotoxic regimens, with bevacizumab 5–7.5 mg/kg q21 days in combination with either carboplatin (n = 8), oral cyclofosfamide (n = 5) or weekly paclitaxel (n = 2). Bevacizumab was administered until disease progression. Tumor response was assessed by CA125 and fusion 18 F-FDG PET/contrast enhanced CT.ResultsThe median number of bevacizumab cycles was 21 (range 3–59). The median baseline CA125 was 272 U/ml and decreased to 15.2 U/ml at nadir. Tumor response was 4 complete response (CR) (26.7%) and 7 partial response (PR) (46.7%) by chemotherapy (CT), with an overall response rate of 73.4% (95% CI, 51.0 – 95.8) according to Response Evaluation Criteria In Solid Tumors (RECIST), and 6 CR (40%) and 4 PR (26.7%) by PET, for an overall metabolic response rate of 67% (95%CI, 42.8 – 90.6) according to PET Response Criteria in Solid Tumors (PERCIST). Median progression free survival (PFS) was 21 months and median overall survival (OS) was 24 months. Grade 3 adverse events related to bevacizumab were hypertension (n = 2), proteinuria (n = 1) and epistaxis (n = 5). Treatment was delayed in five patients for nasal bleeding or uncontrolled hypertension.ConclusionsLow-dose bevacizumab and chemotherapy was well tolerated and active in a heavily pretreated population of advanced EOC. Further studies should assess the activity of low dose bevacizumab in EOC.

Highlights

  • Ovarian cancer is the most lethal gynecologic malignant tumor in developed countries

  • We explored the activity and safety of 5–7.5 mg/ kg q21 bevacizumab in heavily pretreated patients mostly with platinum resistant epithelial ovarian cancer (EOC)

  • The patients received a median number of four prior cytotoxic regimens

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Summary

Introduction

Ovarian cancer is the most lethal gynecologic malignant tumor in developed countries It is generally diagnosed in advanced stage and cytotoxic chemotherapy is only partially effective. A number of phase-II trials have assessed the activity of bevacizumab in the treatment of recurrent EOC, with promising results [7,8], including patients with platinum resistant disease [9,10,11]. These trials were followed by three randomized phase-3 trial in first-line treatment of EOC: GOG 218, ICON 7 and OCEAN trial [12,13,14].

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