Transcatheter arterial chemoembolization using cisplatin powder mixed with degradable starch microspheres for colorectal liver metastases after FOLFOX failure: results of a phase I/II study.

Abstract

PURPOSE:

To report the results of a phase I/II study of a transcatheter arterial chemoembolization protocol using cisplatin powder and degradable starch microspheres (DSM) for unresectable colorectal liver metastases after failure of FOLFOX (5-flourouracil, leucovorin plus oxaliplatin) chemotherapy conducted to determine the recommended dose of cisplatin powder and to assess the efficacy and safety of the protocol.

MATERIALS AND METHODS:

A fine-powder formulation of cisplatin was mixed with DSM and administered via the hepatic artery every 4 weeks. In phase I, three cohorts of patients received escalating doses of cisplatin powder: 50 mg/m(2), 65 mg/m(2), and 80 mg/m(2). In phase II, tumor response, toxicity, and survival times were assessed.

RESULTS:

The study enrolled 24 patients. Previously, FOLFOX had been administered to all patients, an irinotecan-containing regimen had been administered to 12 patients, and bevacizumab or cetuximab or both had been administered to 14 patients. In phase I, dose-limiting toxicity did not appear at any level, and the recommended dose of cisplatin powder was determined to be 80 mg/m(2). In phase II, a tumor response rate of 61.1% was achieved. The median hepatic progression-free survival and overall survival were 8.8 months (95% confidence interval [CI], 4.06-13.5 mo) and 21.1 months (95% CI, 8.37-33.8 mo). The following grade 3 toxicities were observed: thrombocytopenia (12.5%), aspartate transaminase elevation (33.3%), alanine transaminase elevation (12.5%), hyponatremia (8.3%), and cholecystitis (4.2%).

CONCLUSIONS:

This study shows that transcatheter arterial chemoembolization with cisplatin powder at a dose of 80 mg/m(2) mixed with DSM is well tolerated and can produce a high response rate with a long survival time for patients with unresectable colorectal liver metastases after failure of FOLFOX.

• Authors: Hideyuki Nishiofuku, Toshihiro Tanaka, Masaki Matsuoka, Toshio Otsuji, Hiroshi Anai, Satoru Sueyoshi, Yoshitaka Inaba, Fumikazu Koyama, Masayuki Sho, Yoshiyuki Nakajima, Kimihiko Kichikawa
• Journal: Journal of vascular and interventional radiology : JVIR (J Vasc Interv Radiol) Vol. 24 Issue 1 Pg. 56-65 (Jan 2013) ISSN: 1535-7732 [Electronic] United States
• PMID: 23194749 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article)
• Copyright: Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.

Chemical References

• Drug Combinations
• Organoplatinum Compounds
• Powders
• Starch
• Cisplatin
• Leucovorin
• Fluorouracil

Topics

• Absorbable Implants
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Catheterization, Peripheral
• Chemoembolization, Therapeutic (methods)
• Cisplatin (administration & dosage)
• Colorectal Neoplasms (diagnostic imaging, therapy)
• Drug Combinations
• Embolization, Therapeutic (methods)
• Female
• Fluorouracil (therapeutic use)
• Humans
• Leucovorin (therapeutic use)
• Liver Neoplasms (secondary, therapy)
• Male
• Microspheres
• Middle Aged
• Organoplatinum Compounds (therapeutic use)
• Powders
• Radiography
• Starch (administration & dosage)
• Treatment Failure
• Treatment Outcome