title: Phase I study of CPT-11 and bolus 5-FU/ l-leucovorin in patients with metastatic colorectal cancer.
abstract: BACKGROUND
  Irinotecan (CPT-11) and bolus 5-fluorouracil (5-FU)/leucovorin (LV) administered weekly for 4 weeks every 42 days (Saltz regimen) is active but substantially toxic in patients with metastatic colorectal cancer (CRC). The efficacy and toxicity of this regimen, however, have not been determined in Japanese patients with metastatic CRC.
  
  
  METHODS
  We investigated the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and recommended phase II dose (RD) for CPT-11 given i.v. (90-min infusion) and bolus 5-FU plus biologically active l-LV administered weekly for 3 weeks every 28 days (modified Saltz regimen) in Japanese patients with metastatic CRC. Eighteen patients with measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, and adequate organ functions were enrolled.
  
  
  RESULTS
  At dose level 2 (CPT-11, 100 mg/m(2); 5-FU, 400 mg/m(2); and l-LV, 25 mg/body), 1 of 6 patients had DLT (febrile neutropenia). At dose level 3 (CPT-11, 100 mg/m(2); 5-FU, 500 mg/m(2); and l-LV, 25 mg/body), 2 of 6 patients had DLT (febrile neutropenia and grade 4 neutropenia lasting more than 4 days). To determine whether level 3 was the MTD level, an additional 3 patients were treated at this level, but no DLT was observed. Consequently, 2 of 9 patients had DLT at level 3, this level thus being considered as the RD. At this level, grade 3-4 neutropenia was common but manageable. Nonhematological toxicities were mild. Seven partial responses were observed in the 18 enrolled patients (response rate [RR], 39%), and 8 patients (44%) experienced stable disease.
  
  
  CONCLUSIONS
  This CPT-11/5-FU/ l-LV regimen administered weekly for 3 weeks every 28 days has substantial antitumor activity, with manageable toxicities. A multicenter phase II study is currently underway. Irinotecan (CPT-11) and bolus 5-fluorouracil (5-FU)/leucovorin (LV) administered weekly for 4 weeks every 42 days (Saltz regimen) is active but substantially toxic in patients with metastatic colorectal cancer (CRC). The efficacy and toxicity of this regimen, however, have not been determined in Japanese patients with metastatic CRC.
authors.affiliation: Department of Internal Medicine, Miyazaki Prefectural Hospital, Miyazaki, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Fujishima
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kikuchi
authors.forename: Osamu
authors.initials: O
authors.lastname: Miyanaga
authors.forename: Akira
authors.initials: A
authors.lastname: Ueda
authors.forename: Eishi
authors.initials: E
authors.lastname: Baba
authors.forename: Kenji
authors.initials: K
authors.lastname: Mitsugi
authors.forename: Mine
authors.initials: M
authors.lastname: Harada
authors.forename: Shuji
authors.initials: S
authors.lastname: Nakano
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D005492:Folic Acid / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D005492:Folic Acid; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin