title: Chronomodulated irinotecan, oxaliplatin, and leucovorin-modulated 5-Fluorouracil as ambulatory salvage therapy in patients with irinotecan- and oxaliplatin-resistant metastatic colorectal cancer.
abstract: OBJECTIVE
  To evaluate the activity and tolerability of salvage chronomodulated chemotherapy combining irinotecan (I), 5-fluorouracil/leucovorin (5-FU/LV), and oxaliplatin (O) (chronoIFLO) in patients with metastatic colorectal cancer (MCRC) and prior progression on four drugs.
  
  
  METHODS
  Seventy-seven nonhospitalized MCRC patients received chronoIFLO every 3 weeks, with day 1: I (180 mg/m2 over 6 hours, with peak infusion rate at 05:00) and days 2-5: 5-FU/LV (700/300 mg/m2 per day over 12 hours, with peak flow rate at 04:00), and O (20 mg/m2 per day over 12 hours, with peak flow rate at 16:00). Toxicity and response were assessed every 3 weeks and every 2 months, respectively. RESULTS. Three or more prior chemotherapy lines were given to 75% of the patients. Two or more organs had metastatic disease in 65% of the patients. A median number of six courses of chronoIFLO was given. The main grade 3-4 toxicities were diarrhea (39% of the patients, 9% of the courses) and neutropenia (30% of the patients and 7% of the courses). Grade 3 peripheral sensory neuropathy occurred in 14% of the patients. Two patients achieved a partial response and 61 had stable disease, resulting in disease control for 82% of the patients. The median time to progression (TTP) was 5.5 months (95% confidence interval, 3.7-6.0). The median overall survival time was 14.2 months (9.8-17.3). Baseline performance status, serum carcinoembryonic antigen (CEA) level, and CEA doubling time were independent prognostic factors of TTP.
  
  
  CONCLUSIONS
  ChronoIFLO safely and durably halted tumor progression in most extensively pretreated MCRC patients.
authors.affiliation: INSERM U776 Rythmes Biologiques et Cancers, Hôpital Paul Brousse, Villejuif, France.
authors.forename: Dany
authors.initials: D
authors.lastname: Gholam
authors.forename: Sylvie
authors.initials: S
authors.lastname: Giacchetti
authors.forename: Catherine
authors.initials: C
authors.lastname: Brézault-Bonnet
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bouchahda
authors.forename: Dominique
authors.initials: D
authors.lastname: Hauteville
authors.forename: René
authors.initials: R
authors.lastname: Adam
authors.forename: Béatrice
authors.initials: B
authors.lastname: Ducot
authors.forename: Odile
authors.initials: O
authors.lastname: Ghémard
authors.forename: Francis
authors.initials: F
authors.lastname: Kustlinger
authors.forename: Claude
authors.initials: C
authors.lastname: Jasmin
authors.forename: Francis
authors.initials: F
authors.lastname: Lévi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019454:Chronotherapy; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin