Outcomes of a Phase I/II Trial of Hepatic Arterial Infusion of Oxaliplatin Combined with Intravenous 5-Fluorouracil and l-Leucovorin in Patients with Unresectable Liver Metastases from Colorectal Cancer After Systemic Chemotherapy Failure.

Abstract

The purpose of this study was to assess hepatic arterial infusion (HAI) of oxaliplatin combined with intravenous 5-fluorouracil (5-FU) and l-leucovorin (l-LV) in colorectal cancer (CRC) patients with systemic chemotherapy failure in a phase I/II trial. CRC patients with unresectable liver metastases following standard systemic chemotherapy failure were eligible. A catheter-port system for HAI was placed using interventional radiology. In phase I, escalating doses of oxaliplatin for levels 1 and 2 were set at 50 and 100mg/m2, respectively, and were combined with fixed doses of intravenous 5-FU (200mg/m2 bolus and 2400mg/m2/46-h continuous infusion) and l-LV (200mg/m2). The dose-limiting toxicity (DLT) was assessed, and the recommended dose (RD) was estimated. In phase II, patients receiving RD were included to assess the 6-month survival rate (the expected rate 80%), overall survival time, tumor response, and toxicity. In phase I, none of the six enrolled patients exhibited DLT. RD for oxaliplatin by HAI was estimated as 100mg/m2. In phase II, seven additional patients were enrolled. In patients receiving RD (n = 10), the disease control rates for total lesions and liver lesions were 30 and 70%, respectively. The 6-month survival rate and the overall survival time were 53.3% and 6.9months, respectively. There were no adverse reactions equivalent to DLT in any of the patients. The estimated RD for oxaliplatin by HAI in combination with intravenous 5-FU and l-LV was 100mg/m2. This combination therapy was feasible and safe, but the expected efficacy was not achieved.