A Phase I/II trial of continuous hepatic intra-arterial infusion of 5-fluorouracil, mitoxantrone and cisplatin for advanced hepatocellular carcinoma.
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.


CONCLUSIONS
Hepatic intra-arterial infusion therapy of FMP could not demonstrate a favorable tumor response and overall survival in patients with advanced HCC.
Department of Hepatobiliary & Pancreatic Oncology, National Cancer Center Hospital East.
Masafumi
M
Ikeda
Department of Hepatobiliary & Pancreatic Oncology, National Cancer Center Hospital.
Takuji
T
Okusaka
Department of Interventional and Diagnostic Radiology, Aichi Cancer Center.
Yozo
Y
Sato
Department of Medical Oncology, Kyorin University, Tokyo.
Junji
J
Furuse
Department of Hepatobiliary & Pancreatic Oncology, National Cancer Center Hospital East.
Shuichi
S
Mitsunaga
Department of Hepatobiliary & Pancreatic Oncology, National Cancer Center Hospital.
Hideki
H
Ueno
Department of Hepatobiliary & Pancreatic Oncology, National Cancer Center Hospital.
Chigusa
C
Morizane
Department of Interventional and Diagnostic Radiology, Aichi Cancer Center.
Yoshitaka
Y
Inaba
Department of Diagnostic Radiology, National Cancer Center Hospital.
Tatsushi
T
Kobayashi
Department of Diagnostic Radiology, National Cancer Center Hospital East, Japan.
Yasuaki
Y
Arai
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D057785:Catheters; D002945:Cisplatin / Q000008:administration & dosage* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007261:Infusions, Intra-Arterial; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
D008942:Mitoxantrone; D002945:Cisplatin; D005472:Fluorouracil
5-fluorouracil; cisplatin; hepatocellular carcinoma; intra-arterial chemotherapy; mitoxantrone