Hepatic Arterial Infusion with Irinotecan in Patients with Liver Metastases of Colorectal Cancer: Results of an Extended Phase I Study

Abstract

Background: To define the maximum tolerated dose (MTD) tolerability and efficacy of intra-arterial chemotherapy with irinotecan in patients with liver metastases of colorectal carcinoma (CRC). Methods: Superselective intra-arterial irinotecan was applied on days 1, 14, 28 and 42. The initial dose was 140 mg/m² with escalation in the subsequent patient group to 160 mg/m². The final protocol toxicity evaluation was 260 mg/m². Patients required histologically proven disease and adequate bone marrow, liver and renal function, no extrahepatic metastasis and a life expectancy >12 weeks. Results: Thirty-three patients were enrolled (median age 65, range 49-78 years). On dose level VI (240 mg/m²), 1 case of dose-limiting toxicity (DLT) (granulocytopenia) was observed, leading to an enlarged cohort of 6 patients. As no additional DLT was detected on this level, an escalation to level VII was performed. On the dose level of 260 mg/m², irinotecan DLTs were observed, resulting in the termination of escalation and the declaration of dose level VI as MTD. Imaging follow-up with Response Evaluation Criteria in Solid Tumors (RECIST) criteria revealed a complete response in 1 patient, stable disease in 31 patients, and progressed disease in 1 patient. The median time to progression was 4.7 months, the median overall survival 15.6 months. Conclusion: The method of intra-arterial chemotherapy with irinotecan is well tolerated and shows promising local response rates in liver metastases of CRC.