Masafumi Ikeda1, Takuji Okusaka2, Yozo Sato3, Junji Furuse4, Shuichi Mitsunaga1, Hideki Ueno2, Chigusa Morizane2, Yoshitaka Inaba3, Tatsushi Kobayashi5, Yasuaki Arai6. 1. Department of Hepatobiliary & Pancreatic Oncology, National Cancer Center Hospital East. 2. Department of Hepatobiliary & Pancreatic Oncology, National Cancer Center Hospital. 3. Department of Interventional and Diagnostic Radiology, Aichi Cancer Center. 4. Department of Medical Oncology, Kyorin University, Tokyo. 5. Department of Diagnostic Radiology, National Cancer Center Hospital. 6. Department of Diagnostic Radiology, National Cancer Center Hospital East, Japan.
Abstract
BACKGROUND: The aim of this study was to investigate the dose-limiting toxicities (DLTs) and determine the recommended doses in the Phase I part of the study, and to evaluate the efficacy and toxicity in the Phase II part, of continuous hepatic intra-arterial infusion therapy with 5-fluorouracil, mitoxantrone and cisplatin (FMP therapy) in patients with advanced hepatocellular carcinoma (HCC). METHODS: Forty-five patients with advanced HCC were enrolled. The therapy consisted of continuous intra-arterial infusion of 5-fluorouracil from Day 1 through Day 5, and intra-arterial administration of mitoxantrone and cisplatin on Day 1 [5-fluorouracil/mitoxantrone/cisplatin (mg/m2): Level 1; 400/4/60, Level 2; 400/6/60, Level 3; 500/6/60]. RESULTS: In the Phase I part of the study, one of the six patients at Level 1 developed DLTs, including Grade 3 pulmonary embolism, while none of the patients at either Level 2 or Level 3 exhibited any DLTs. In the Phase II part, at Level 3, 36 patients were enrolled. Nine patients (25%) showed partial response, representing a response rate of 25% (95% confidence interval: 12-42%). The overall median survival time, 1-year survival rate and median progression-free survival time were 11.3 months, 46.9% and 7.0 months, respectively. The main Grade 3 or 4 hematological and non-hematological toxicities were leukopenia (36%), neutropenia (39%), thrombocytopenia (19%), and elevated serum aspartate aminotransferase (22%), elevated serum alanine aminotransferase (14%) and occlusion of hepatic artery (22%), respectively. CONCLUSION: Hepatic intra-arterial infusion therapy of FMP could not demonstrate a favorable tumor response and overall survival in patients with advanced HCC.
BACKGROUND: The aim of this study was to investigate the dose-limiting toxicities (DLTs) and determine the recommended doses in the Phase I part of the study, and to evaluate the efficacy and toxicity in the Phase II part, of continuous hepatic intra-arterial infusion therapy with 5-fluorouracil, mitoxantrone and cisplatin (FMP therapy) in patients with advanced hepatocellular carcinoma (HCC). METHODS: Forty-five patients with advanced HCC were enrolled. The therapy consisted of continuous intra-arterial infusion of 5-fluorouracil from Day 1 through Day 5, and intra-arterial administration of mitoxantrone and cisplatin on Day 1 [5-fluorouracil/mitoxantrone/cisplatin (mg/m2): Level 1; 400/4/60, Level 2; 400/6/60, Level 3; 500/6/60]. RESULTS: In the Phase I part of the study, one of the six patients at Level 1 developed DLTs, including Grade 3 pulmonary embolism, while none of the patients at either Level 2 or Level 3 exhibited any DLTs. In the Phase II part, at Level 3, 36 patients were enrolled. Nine patients (25%) showed partial response, representing a response rate of 25% (95% confidence interval: 12-42%). The overall median survival time, 1-year survival rate and median progression-free survival time were 11.3 months, 46.9% and 7.0 months, respectively. The main Grade 3 or 4 hematological and non-hematological toxicities were leukopenia (36%), neutropenia (39%), thrombocytopenia (19%), and elevated serum aspartate aminotransferase (22%), elevated serum alanine aminotransferase (14%) and occlusion of hepatic artery (22%), respectively. CONCLUSION: Hepatic intra-arterial infusion therapy of FMP could not demonstrate a favorable tumor response and overall survival in patients with advanced HCC.