Phase I study of intraperitoneal bevacizumab for treating refractory malignant ascites

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.

Tumor vessel normalization and immunotherapy in gastric cancer

“… 168 A research study showed that an intraperitoneal injection of bevacizumab in patients with advanced ascites tumors activates the immune system, leading to an increase in effector CD8+ T-cell counts. 55 A clinical trial of patients with advanced GC/GEJC evaluating the efficacy of ramucirumab plus pembrolizumab combination showed encouraging clinical activity and manageable toxicity. 107 In the REGONIVO study, the combination of regorafenib and nivolumab showed remarkable anti-tumor activity (ORR = 44%) in patients with GC who had shown a poor response to prior therapy.…”

“…51 The concentration of pro-angiogenic factors in ascites is an indicator of poor tumor prognosis and correlates with tumor aggressiveness. 52 Ascites is a poor prognostic factor and one of the most common complications in advanced GC, with nearly half of patients with advanced disease having ascites 53,54 ; this condition is characterized by high abundance of pro-angiogenic factors 55 and immunosuppressive cells. 53 Patients with malignant ascites show a rapidly deteriorating clinical course and often have a short survival rate.…”

Curative Effect Evaluation of Intraperitoneal Hyperthermic Perfusion Chemotherapy Combined With Apatinib for Malignant Ascites

“…Hyperthermic perfusion treatment could destroy tumour cells without damaging normal tissues. It can effectively wipe out free cancer cells and remnants of tiny cancer metastases in the body cavity, and has a positive effect on improving the overall efficacy of cancer treatment and preventing cancer recurrence [19]. The clinical evaluation revealed that intraperitoneal hyperthermic perfusion chemotherapy can significantly improve the status of 80% patients with ascites.…”

Current Treatments and New Possible Complementary Therapies for Epithelial Ovarian Cancer

“…Similarly, a phase I study in patients with diverse cancers tested intraperitoneal bevacizumab for treating refractory malignant ascites. Preliminary results of this study showed that bevacizumab exhibited short-term anti-tumoral efficacy and palliated symptoms [ 94 ]. Given that over one-third of women with ovarian cancer will develop ascites [ 95 ], bevacizumab therapy should be considered in this subgroup of patients.…”