title: Intermittent versus continuous chemotherapy in advanced colorectal cancer: a randomised 'GISCAD' trial.
abstract: BACKGROUND
  In advanced colorectal cancer, chemotherapy is usually administered without pauses and until progression but patients can experience cumulative toxicity and cannot tolerate a heavy therapeutic charge.
  
  
  OBJECTIVE
  The aim of the present trial was to evaluate whether an intermittent chemotherapy with levo-leucovorin + 5-fluorouracil (5-FU) + irinotecan (CPT-11) was at least as effective as the same regimen given continuously, both administered until progression, in patients affected with advanced colorectal cancer and not previously exposed to chemotherapy for metastatic disease.
  
  
  METHODS
  A total of 337 patients from 27 institutions were randomised between levo-leucovorin, 100/mg/m(2) i.v. + 5-FU; 400 mg/m(2) i.v. bolus + 5-FU; 600 mg/m(2) 22-h continuous infusion, days 1 and 2 + CPT-11; 180 mg/m(2) day 1, administered every 2 weeks 2 months on and 2 months off (arm A) and the same regimen administered continuously (arm B), until progression in both arms. The main end point was overall survival (OS), the secondary progression-free survival (PFS) and toxicity.
  
  
  RESULTS
  At a median follow-up of 41 months, OS was 18 months in arm A and 17 months in arm B [hazard ratio (HR), 0.88]. Also PFS was comparable in the two groups (6 months in both, with HR, 1.03), and even grades 3-4 toxicity (mainly myelosuppression, fever and diarrhoea) was similar. Second-line oxaliplatin-based treatment was administered in a similar percentage (66%) in the two arms. The median chemotherapy-free period (drug holiday) in arm A was 3.5 months.
  
  
  CONCLUSIONS
  Reducing the charge of therapy in this population did not diminish the efficacy of treatment. Further studies with this strategy, including biologicals, are warranted.
authors.affiliation: Oncologia Medica, Ospedali Riuniti, Bergamo. Electronic address: rlabian@tin.it.
authors.forename: R
authors.initials: R
authors.lastname: Labianca
authors.affiliation: Oncologia Medica, Ospedale S.Martino, Genova.
authors.forename: A
authors.initials: A
authors.lastname: Sobrero
authors.affiliation: Oncologia Medica, Ospedale Serbelloni, Gorgonzola, Milan.
authors.forename: L
authors.initials: L
authors.lastname: Isa
authors.affiliation: Oncologia Medica, Policlinico Umberto I, Roma.
authors.forename: E
authors.initials: E
authors.lastname: Cortesi
authors.affiliation: Oncologia Medica, Ospedale Treviglio-Caravaggio, Treviglio.
authors.forename: S
authors.initials: S
authors.lastname: Barni
authors.affiliation: Oncologia Medica, A.O. S.Giuseppe Moscati, Avellino.
authors.forename: D
authors.initials: D
authors.lastname: Nicolella
authors.affiliation: Oncologia Medica, Istituto Ricerca e Cura del Cancro, Candiolo.
authors.forename: M
authors.initials: M
authors.lastname: Aglietta
authors.affiliation: Oncologia Medica, Istituto Oncologico Veneto, Padova.
authors.forename: S
authors.initials: S
authors.lastname: Lonardi
authors.affiliation: Oncologia, Ospedale Fatebenefratelli-Isola Tiberina, Roma.
authors.forename: D
authors.initials: D
authors.lastname: Corsi
authors.affiliation: Oncologia e Ematologia, A.O. S.Maria delle Croci, Ravenna.
authors.forename: D
authors.initials: D
authors.lastname: Turci
authors.affiliation: Oncologia Medica, Ospedali Riuniti, Bergamo.
authors.forename: G D
authors.initials: GD
authors.lastname: Beretta
authors.affiliation: Oncologia Medica, Ospedale S.Martino, Genova.
authors.forename: G
authors.initials: G
authors.lastname: Fornarini
authors.affiliation: Oncology Department, A.O. Ospedale S.Gerardo, Monza.
authors.forename: E
authors.initials: E
authors.lastname: Dapretto
authors.affiliation: Laboratorio di Epidemiologia, Clinica Istituto, Ricerche Farmacologiche Mario Negri, Milano.
authors.forename: I
authors.initials: I
authors.lastname: Floriani
authors.affiliation: Oncologia Medica, Fondazione Poliambulanza, Brescia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Zaniboni
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D058766:Levoleucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D058766:Levoleucovorin; D005472:Fluorouracil; D002166:Camptothecin