title: Activity and safety of a low dose, fractional administration of irinotecan hydrochloride (CPT-11) in combination with cisplatin for relapsed gastric cancer patients: a preliminary report.
abstract: BACKGROUND
  Irinotecan hydrochloride (CPT-11) in combination with cisplatin has emerged as a new therapeutic option for the treatment of advanced gastric cancer. So far, very few combination trials have been reported, and a relatively high frequency of grade 3/4 toxicities in previous trials has been a major problem. The purpose of this study was to elucidate the efficacy and safety of a low dose, fractional administration of CPT-11 and cisplatin that is principally based on recently acquired knowledge of the synergistic antitumor activities between these two agents.
  
  
  METHODS
  Five relapsed gastric cancer patients were treated every 2 weeks with a starting dose of CPT-11 (30 mg/m(2)) and a fixed dose of cisplatin (30 mg/m(2)). All patients were of performance status 0 and had received prior chemotherapy. Dose escalation of CPT-11 to 40 mg/m(2) or to 50 mg/m(2) was performed whenever possible. Responses, toxicities, and at-home ratio during chemotherapy were evaluated.
  
  
  RESULTS
  The response rate reached 40%. Toxicities were grade 1/2, and no grade 3/4 hematological toxicities or diarrhea were observed. Repeated subsequent treatments could be performed in an outpatient setting without treatment delay or cancellations, which resulted in an 83%-92% at-home ratio in four patients receiving five or more cycles of treatment. There were no treatment-related deaths.
  
  
  CONCLUSIONS
  A low dose, fractional administration of CPT-11 and cisplatin seems rational, encouraging, and safe, and compares well with other trials of the combination. Outpatient administration provides the patients with a better quality of life, suggesting a meaningful therapeutic option for relapsed gastric cancer patients in particular.
authors.affiliation: Department of Gastrointestinal Surgery, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. shimoyama-dis@h.u-tokyo.ac.jp
authors.forename: Shouji
authors.initials: S
authors.lastname: Shimoyama
authors.forename: Fumio
authors.initials: F
authors.lastname: Aoki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shimizu
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tatsutomi
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Mafune
authors.forename: Michio
authors.initials: M
authors.lastname: Kaminishi
mesh_terms: D000368:Aged; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D002166:Camptothecin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D000077146:Irinotecan; D007564:Japan; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin