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

J Vasc Interv Radiol. 2013 Jan;24(1):56-65. doi: 10.1016/j.jvir.2012.09.010. Epub 2012 Nov 26.

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.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

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

Substances

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

Supplementary concepts

  • Folfox protocol