title: A multicenter phase II study of irinotecan (CPT-11) alternated with 5-fluorouracil and leucovorin as first-line treatment of patients with metastatic colorectal cancer.
abstract: OBJECTIVE
  In this multicenter phase II study the efficacy and safety of the alternating schedule of irinotecan (CPT-11) with bolus 5-fluorouracil (5-FU) and leucovorin (LV) were assessed as first-line chemotherapy in patients with metastatic colorectal cancer (CRC).
  
  
  METHODS
  Enrolled in the study were 43 patients with advanced CRC. They received CPT-11 350 mg/m2 i.v. on day 1, alternating with LV 20 mg/m2 i.v. and 5-FU 425 mg/m2 i.v. daily for five consecutive days, on days 22-26 (Mayo Clinic regimen). One cycle consisted of 6 weeks.
  
  
  RESULTS
  A total of 179 cycles were administered with a median of four per patient (range one to nine). Efficacy was analyzed on an intention-to-treat basis. The overall objective response rate was 30% (95% CI 16-44), with four complete responses and nine partial responses, whereas 20 patients (4%) showed stable disease. The median time to disease progression was 9.0 months and median survival was 18.5 months. Grade 3/4 diarrhea was mainly related to CPT-11 rather than to 5-FU (9.3% vs 4.7% of patients), whereas grade 3/4 neutropenia was higher during 5-FU administration (16.3% vs 7.0% of patients).
  
  
  CONCLUSIONS
  The alternating schedule of CPT-11 with 5 days bolus of 5-FU and low-dose LV showed a clinical benefit in terms of tumor growth control as first-line treatment of patients with metastatic CRC. The overall safety data confirmed this alternating combination as a well-tolerated treatment.
authors.affiliation: Hospital Juan Ramón Jiménez, Huelva, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Reina
authors.forename: Jorge
authors.initials: J
authors.lastname: Aparicio
authors.forename: Javier
authors.initials: J
authors.lastname: Salvador
authors.forename: José María Puerto
authors.initials: JM
authors.lastname: Pica
authors.forename: Antonio
authors.initials: A
authors.lastname: Rueda
authors.forename: Antonio
authors.initials: A
authors.lastname: Lorenzo
authors.forename: Carlos González
authors.initials: CG
authors.lastname: de la Puente
authors.forename: Pablo
authors.initials: P
authors.lastname: Borrega
authors.forename: José Andrés
authors.initials: JA
authors.lastname: Moreno-Nogueira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000931:Antidotes / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D002955:Leucovorin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016019:Survival Analysis
chemical_list: D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin