Yozo Sato1, Yoshitaka Inaba2, Takashi Ura3, Hideyuki Nishiofuku4, Hidekazu Yamaura2, Mina Kato2, Daisuke Takahari3, Toshihiro Tanaka4, Kei Muro3. 1. Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. ysato@aichi-cc.jp. 2. Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. 3. Department of Medical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. 4. Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan.
Abstract
PURPOSE: 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. METHODS: 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 100 mg/m2, respectively, and were combined with fixed doses of intravenous 5-FU (200 mg/m2 bolus and 2400 mg/m2/46-h continuous infusion) and l-LV (200 mg/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. RESULTS: In phase I, none of the six enrolled patients exhibited DLT. RD for oxaliplatin by HAI was estimated as 100 mg/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 6.9 months, respectively. There were no adverse reactions equivalent to DLT in any of the patients. CONCLUSIONS: The estimated RD for oxaliplatin by HAI in combination with intravenous 5-FU and l-LV was 100 mg/m2. This combination therapy was feasible and safe, but the expected efficacy was not achieved.
PURPOSE: 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. METHODS:CRCpatients 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 100 mg/m2, respectively, and were combined with fixed doses of intravenous 5-FU (200 mg/m2 bolus and 2400 mg/m2/46-h continuous infusion) and l-LV (200 mg/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. RESULTS: In phase I, none of the six enrolled patients exhibited DLT. RD for oxaliplatin by HAI was estimated as 100 mg/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 6.9 months, respectively. There were no adverse reactions equivalent to DLT in any of the patients. CONCLUSIONS: The estimated RD for oxaliplatin by HAI in combination with intravenous 5-FU and l-LV was 100 mg/m2. This combination therapy was feasible and safe, but the expected efficacy was not achieved.
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