Phase I study of intraperitoneal bevacizumab for treating refractory malignant ascites

Furong Kou, Jifang Gong, Yan Li, Jian Li, Xiaotian Zhang, Jie Li, Lin Shen, Furong Kou, Jifang Gong, Yan Li, Jian Li, Xiaotian Zhang, Jie Li, Lin Shen

Abstract

Objective: This prospective, dose-escalation phase I study evaluated the safety and efficacy of intraperitoneal bevacizumab in managing refractory malignant ascites and explored the recommended dose of bevacizumab for further study.

Methods: Patients with refractory malignant ascites were enrolled. Bevacizumab was intraperitoneal administered weekly at an initial dose of 2.5 mg/kg, with dose escalation to 5 and 7.5 mg/kg performed following the standard "3 + 3" rule. The total duration of treatment was 2 or 3 weeks.

Results: Between December 2013 and September 2014, 13 patients (2.5 mg/kg, n = 4; 5 mg/kg, n = 3; 7.5 mg/kg, n = 6) with refractory malignant ascites were enrolled. Bevacizumab was well tolerated, and the most common treatment-related adverse events were abdominal pain (5/13), abdominal distension (2/13), and fatigue (2/13). The dose-limiting toxicity at 7.5 mg/kg was grade 3 bowel obstruction (1/13). The maximum tolerated dose (MTD) was not reached. The overall response and disease control rates were 7.7 and 61.5%, respectively.

Conclusions: Intraperitoneal bevacizumab safe and well tolerated for treating malignant ascites, and the MTD was not reached at doses of 2.5 to 7.5 mg/kg. Intraperitoneal bevacizumab at 7.5 mg/kg weekly is recommended for further study to verify its anti-tumor activity.Trial registration: Clinical Trials NCT01852409.

Keywords: Bevacizumab; cancer; dose-limiting toxicity; intraperitoneal treatment; malignant ascites; maximum tolerate dose; phase I study; vascular endothelial growth factor.

Conflict of interest statement

Declaration of conflicting interest: Shanghai Roche Pharmaceuticals Limited provided bevacizumab (Avastin®) in this study, as well as revised the article. The authors declare no other conflicts of interest.

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