Open-label safety and efficacy pilot trial of intraperitoneal bevacizumab as palliative treatment in refractory malignant ascites

Abstract

9043 Background: One of the most burdensome complications of advanced cancer is the development of malignant ascites, impacting quality of life (QoL), gastrointestinal function, survival, and overall management costs. Recent studies have shown that malignant effusions arise in part from increased production and activity of vascular endothelial growth factors (VEGFs). VEGFs increase vascular permeability and establish an ideal environment for accumulation of malignant effusions. Methods: A pilot trial evaluating safety and efficacy of intraperitoneal administration of bevacizumab at 5 mg/kg monthly for as long as no disease progression or unacceptable toxicities are encountered. Patients with cytologically documented malignant ascites from any primary tumor refractory to standard therapy of diuretics, repeated paracentesis, and/or intraperitoneal chemotherapy were eligible. Patients were either off systemic therapy or had not had any changes in their systemic therapy for at least 4 weeks at the time of enrollment. Results: Between July 2006 and November 2006, 9 patients with refractory malignant ascites from colon cancer (3 pts), breast cancer (3 pts), uterine cancer (2 pts) and ovarian cancer (1 pt). Prior therapy included systemic chemotherapy and large volume paracentesis. Patients with ovarian and uterine cancer also received intraperitoneal cisplatin. All patients had rapid re-accumulation within 2 weeks of paracentesis before treatment. Patients were given intraperitoneal bevacizumab at 5 mg/kg monthly. Complications included grade I nausea in one patient, grade I abdominal pain in one patient, and partial small bowel obstruction in one patient that was managed conservatively. Malignant ascites resolved without reaccumulation or repeat paracentresis in 9/9 after a single intraperitoneal dose of bevacizumab over a median observation period of over two months. No objective tumor responses were observed. QoL assessment, pharmacokinetic studies of intraperitoneal Bevacizumab and pharmacodynamic studies on serum and ascites fluid VEGF are ongoing and will be reported. Conclusions: Intraperitoneal bevacizumab is a relatively safe and highly efficacious way to palliate the symptoms of refractory malignant ascites. No significant financial relationships to disclose.

Sustained response of malignant pericardial effusion to intrapericardial bevacizumab in an advanced lung cancer patient: a case report and literature review

“…El-Shami et al reported that an 82-year-old woman with refractory ovarian cancer and malignant ascites received an intraperitoneal perfusion of bevacizumab, after which her ascites symptoms were alleviated without any adverse reaction. 15 Numnum et al reported symptomatic relief of ascites without grade 3/4 toxicity in four patients after intraperitoneal bevacizumab treatment. They concluded that bevacizumab might be a viable palliative option in patients with end-stage ovarian carcinoma who have symptomatic ascites.…”

Ascites in Advanced Ovarian Cancer

“…dose (5 mg/kg) without re-accumulation or repeat paracentesis over a median observation period >2 months. Moreover, no grade 2-5 adverse events were observed [50]. To evaluate the great potential that preclinical data and clinical case reports have suggested for i.p.…”

The management of malignant ascites and impact on quality of life outcomes in women with ovarian cancer

“…With a follow-up of 6 months, intravenous bevacizumab use led to symptomatic relief in all patients, with manageable toxicity and no further paracenteses [47]. Intraperitoneal bevacizumab has also been assessed, with promising results [48, 63, 64]. In the largest series, which evaluated nine patients with colorectal, breast, uterine or ovarian cancer, intraperitoneal bevacizumab led to the resolution of refractory ascites in all patients.…”

“…In the largest series, which evaluated nine patients with colorectal, breast, uterine or ovarian cancer, intraperitoneal bevacizumab led to the resolution of refractory ascites in all patients. There was no need for repeat paracenteses over a median follow-up of >2 months, and no reported grade 2–5 adverse events [63]. When added to the survival outcomes from the GOG 218 subgroup analysis and the QOL results from the AURELIA trial, these data suggest that bevacizumab may have an important role in the management of patients with advanced/recurrent ovarian cancer with ascites.…”