title: 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: OBJECTIVE
  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.
  
  
  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.affiliation: Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Nara, Japan. hmn@naramed-u.ac.jp
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Nishiofuku
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Masaki
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Toshio
authors.initials: T
authors.lastname: Otsuji
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Anai
authors.forename: Satoru
authors.initials: S
authors.lastname: Sueyoshi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Inaba
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Koyama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sho
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kichikawa
mesh_terms: D020341:Absorbable Implants; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002406:Catheterization, Peripheral; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy*; D004338:Drug Combinations; D004621:Embolization, Therapeutic / Q000379:methods*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000556:secondary* / Q000628:therapy*; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D011208:Powders; D011859:Radiography; D013213:Starch / Q000008:administration & dosage*; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D009944:Organoplatinum Compounds; D011208:Powders; D013213:Starch; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil