title: High dose-intensity of irinotecan administered every 3 weeks in advanced cancer patients: a feasibility study.
abstract: OBJECTIVE
  To assess, on a multicenter basis, the feasibility of treating advanced cancer patients with high-dose irinotecan.
  
  
  METHODS
  Thirty-five patients who met the usual phase I criteria (26 men and nine women) were included. Primary tumor sites were colon, head and neck, unknown primary, kidney, liver, and others. All had been previously treated. Irinotecan was given at the maximum-tolerated dose (MTD) (600 mg/m2) or the level below (500 mg/m2) as a 30-minute infusion once every 3 weeks.
  
  
  RESULTS
  Eighteen patients were entered in the four participating centers at the MTD of 600 mg/m2. This dose level was clearly shown not to be feasible: 14 patients (78%) had grade 3 to 4 neutropenia, with febrile episodes in 11 patients; grade 3 to 4 diarrhea was observed in nine patients; and one toxic death occurred. Subsequently, 17 not heavily pretreated patients were included at 500 mg/m2 and carefully monitored. The safety of this dose level was considered acceptable: 41% of patients had grade 3 to 4 neutropenia, 24% experienced grade 3 to 4 diarrhea, and no febrile granulocytopenia or toxic death occurred. Six partial responses were documented in metastatic colorectal cancer, all in patients who had previously received conventional chemotherapy, four in patients who had exhibited progressive disease under fluorouracil (5FU)-based chemotherapy.
  
  
  CONCLUSIONS
  We plan to study the higher dose-intensity 500-mg/m2 level on good-risk and carefully monitored patients. This could enlarge the spectrum of tumors sensitive to irinotecan and improve the already good results observed in colorectal cancers.
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, Lyon, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Merrouche
authors.forename: J M
authors.initials: JM
authors.lastname: Extra
authors.forename: D
authors.initials: D
authors.lastname: Abigerges
authors.forename: R
authors.initials: R
authors.lastname: Bugat
authors.forename: G
authors.initials: G
authors.lastname: Catimel
authors.forename: E
authors.initials: E
authors.lastname: Suc
authors.forename: M
authors.initials: M
authors.lastname: Marty
authors.forename: P
authors.initials: P
authors.lastname: Hérait
authors.forename: M
authors.initials: M
authors.lastname: Mahjoubi
authors.forename: J P
authors.initials: JP
authors.lastname: Armand
mesh_terms: D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D003967:Diarrhea / Q000139:chemically induced; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin