Joann Lim

Exploratory Study of Hepatic Arterial Infusion Oxaliplatin With Systemic 5-Fluorouracil/ Bevacizumab in Patients With Refractory Solid Tumor and Extensive Liver Metastases

PURPOSE This pilot clinical trial explored the feasibility, safety, and efficacy of regional hepatic therapy combined with systemic anticancer agents in patients with refractory solid tumors and extensive unresectable liver involvement, including those with compromised hepatic function. PATIENTS AND METHODS Six patients with colorectal (N = 3), ovarian (N = 2), and hepatocellular carcinoma (N = 1) received intra-arterial hepatic oxaliplatin followed by intravenous 5-fluorouracil, leucovorin, and bevacizumab every 2 weeks until disease progression. All had extensive liver metastases; four had elevated baseline serum total bilirubin. Median total bilirubin was 2.8 mg/dL (range, 0.2-5.2 mg/dL). Median Child-Pugh score was 7 (range, 5-10). RESULTS Thirty treatments were delivered (2-7 per patient). Median age of patients was 57 years (range, 25-69 years). Three patients (1 with colorectal, 1 with hepatocellular, and 1 with ovarian cancer) attained partial responses. Two had failed previous oxaliplatin and cisplatin treatment. Some with elevated bilirubin at baseline had a significant drop in bilirubin with treatment (bilirubin 5.2 → 1 mg/dL, 4.8 → 1.1 mg/dL, and 5.2 → 1.8 mg/dL). The regimen was generally well tolerated; the most common side effects were grade 1 fatigue, anorexia, and/or hypertension. One patient died of enzyme-linked, immunoassay-confirmed, heparin-induced thrombocytopenia during the sixth cycle of therapy. CONCLUSION At doses tested, this regimen was safe and demonstrated antitumor activity in patients with advanced refractory malignancies involving the liver, including those with hepatic insufficiency. Further study is warranted.

A phase I study of hepatic arterial infusion of oxaliplatin plus intravenous fluorouracil, leucovorin, and bevacizumab in patients with predominant hepatic metastases

2534 Background: The liver is a common site of metastatic involvement in advanced cancer patients. Hepatic arterial infusion (HAI) displayed benefit on overall and progression-free survival. HAI oxaliplatin plus intravenous fluorouracil (5FU) and leucovorin (LV) was well tolerated and effective in those with inoperable colorectal cancer. Pilot data from our group suggested that this proposed regimen could induce responses in patients who had failed systemic therapy including those with compromised hepatic function. We therefore initiated a formal trial of this regimen. Methods: Cohorts of 3–6 patients with predominant hepatic metastases with serum bilirubin less than 3.0 mg/dL will receive escalating dose of HAI oxaliplatin (ranging from 60 mg/m2 to 150 mg/m2 over 2 hours) followed by the standard LV/5FU2 protocol plus intravenous bevacizumab 10 mg/kg once every 3 weeks. Results: Of enrolled 38 patients, toxicities and responses were evaluated. Six dose levels were escalated. DLT was observed in 2 out of ...