title: Phase II study of irinotecan in the treatment of advanced colorectal cancer in chemotherapy-naive patients and patients pretreated with fluorouracil-based chemotherapy.
abstract: OBJECTIVE
  To assess the efficacy of irinotecan (CPT-11) in the treatment of advanced colorectal cancer in both chemotherapy-naive and pretreated patients.
  
  
  METHODS
  Two hundred thirteen patients (aged 18 to 75 years) with metastatic colorectal cancer, World Health Organization (WHO) performance status < or = 2, and life expectancy > or = 3 months were treated with CPT-11 350 mg/m2 every 3 weeks. All 178 patients eligible for efficacy analysis had not received more than one prior fluorouracil (5-FU)-based chemotherapy regimen (adjuvant or palliative) and had adequate hematologic, renal, and hepatic function.
  
  
  RESULTS
  Primary tumor sites were the colon (71%) and rectum (28%). Sixty-six percent of the patients had > or = two metastatic sites. Ninety-eight percent of the patients had undergone previous surgery, and 77.5% had received prior chemotherapy. Thirty-two of 178 eligible patients achieved on objective response (four complete responses [CRs] and 28 partial responses [PRs]; response rate, 18%; 95% confidence interval, 12.6% to 24.4%), 65 were stable, and 59 progressed. The response rate was 17.7% in the pretreated group and 18.8% in the chemotherapy-naive group. Within the former subgroup, response rates of 16.1% were reported in patients who were progressive on prior 5-FU chemotherapy and 19.1% in patients who were progressive off such treatment. The median duration of objective response (9.1 months) and median time to achievement of a response (9.3 weeks) did not differ between chemotherapy-naive and pretreated patients. The most frequent adverse events were neutropenia, which developed in 80% of the patients, delayed diarrhea (87%), alopecia (88%), fatigue (81%), and nausea/vomiting (77%). All these adverse events were manageable. Severe (WHO grade 3 or 4) neutropenia was only observed in 18% of the cycles, leukopenia in 11%, delayed diarrhea in 11%, and nausea and vomiting in 3%. Development of simultaneous grade 3 or 4 neutropenia and delayed diarrhea during 4% of the cycles was the safety issue of greatest concern.
  
  
  CONCLUSIONS
  CPT-11 has definite activity in the treatment of advanced metastatic colorectal cancer both in chemotherapy-naive and in pretreated patients who experienced disease progression on 5-FU, which suggests a lack of cross-resistance between CPT-11 and 5-FU. Diarrhea and neutropenia, the major toxicities of CPT-11, contribute to the risk to develop febrile neutropenic sepsis.
authors.affiliation: Institut Gustave Roussy, Villejuif, France.
authors.forename: P
authors.initials: P
authors.lastname: Rougier
authors.forename: R
authors.initials: R
authors.lastname: Bugat
authors.forename: J Y
authors.initials: JY
authors.lastname: Douillard
authors.forename: S
authors.initials: S
authors.lastname: Culine
authors.forename: E
authors.initials: E
authors.lastname: Suc
authors.forename: P
authors.initials: P
authors.lastname: Brunet
authors.forename: Y
authors.initials: Y
authors.lastname: Becouarn
authors.forename: M
authors.initials: M
authors.lastname: Ychou
authors.forename: M
authors.initials: M
authors.lastname: Marty
authors.forename: J M
authors.initials: JM
authors.lastname: Extra
authors.forename: J
authors.initials: J
authors.lastname: Bonneterre
authors.forename: A
authors.initials: A
authors.lastname: Adenis
authors.forename: J F
authors.initials: JF
authors.lastname: Seitz
authors.forename: G
authors.initials: G
authors.lastname: Ganem
authors.forename: M
authors.initials: M
authors.lastname: Namer
authors.forename: T
authors.initials: T
authors.lastname: Conroy
authors.forename: S
authors.initials: S
authors.lastname: Negrier
authors.forename: Y
authors.initials: Y
authors.lastname: Merrouche
authors.forename: F
authors.initials: F
authors.lastname: Burki
authors.forename: M
authors.initials: M
authors.lastname: Mousseau
authors.forename: P
authors.initials: P
authors.lastname: Herait
authors.forename: M
authors.initials: M
authors.lastname: Mahjoubi
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever / Q000209:etiology; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D012004:Rectal Neoplasms / Q000188:drug therapy*; D012074:Remission Induction
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin