A phase I clinical trial of hepatic arterial infusion of oxaliplatin and oral capecitabine, with or without intravenous bevacizumab, in patients with advanced cancer and predominant liver involvement

Background: We investigated hepatic arterial infusion (HAI) oxaliplatin combined with capecitabine +/− bevacizumab in advanced cancer with predominant liver involvement. Methods: Patients received HAI oxaliplatin (140 mg/m²) and escalating doses of capecitabine (500, 750, and 1000 mg/m²), with (Group 1) or without (Group 2) bevacizumab (10 mg/kg IV). A 3 + 3 dose design was used, followed by an expansion phase. Results: From 9/2009 to 2/2014, 61 patients (34 men, 27 women) were enrolled (Group 1 = 44; Group 2 = 17). Patients were treated in Group 2 if they had contraindications to bevacizumab (n = 13) or if there was no opening in Group 1 (n = 4). The median age was 60 years (range, 20–88). The most common cancers were colorectal (22 patients), liver (12), pancreatic (7), breast (4), and biliary tract (4). The median number of prior therapies was 3 (range, 1–12); 32 (53%) patients had received oxaliplatin. The dose-limiting toxicity was Grade 3 diarrhea and occurred in 2 patients receiving 1000 mg/m² capecitabine. The maximum tolerated dose was HAI oxaliplatin 140 mg/m², capecitabine 750 mg/m², and bevacizumab 10 mg/kg. The most common toxicities were nausea/vomiting, anemia, thrombocytopenia, neutropenia, and hypomagnesemia. The rates of partial response and stable disease ≥ 4 months were 22% and 39% (Group 1) and 9% and 0% (Group 2). The respective median time to treatment failure and overall survival were 3 and 6.9 months (Group 1) and 1.5 and 5.9 months (Group 2). Conclusion: HAI oxaliplatin combined with capecitabine +/− bevacizumab was well-tolerated and was associated with favorable outcomes in selected patients.