title: High activity and reduced neurotoxicity of bi-fractionated oxaliplatin plus 5-fluorouracil/leucovorin for elderly patients with advanced colorectal cancer.
abstract: BACKGROUND
  The proportion of elderly within the general population is increasing and the incidence of colorectal cancer increases with age. Oxaliplatin and 5-fluorouracil (FU) combination is active in this disease.
  
  
  METHODS
  This multicenter phase II study was designed to investigate feasibility, efficacy, activity of daily living (ADL) and instrumental activity of daily living (IADL) in elderly patients with metastatic colorectal cancer treated, as first-line chemotherapy, with a bi-fractionated oxaliplatin/5-FU based regimen. Treatment was oxaliplatin 45 mg/m2, leucovorin 200 mg/m2, 5-FU 400 mg/m2 and 22 h continuous infusion of 5-FU 600 mg/m2, all given intravenously on days 1 and 2, every 2 weeks.
  
  
  RESULTS
  Seventy-eight patients were enrolled; median age was 75 years (range 70-85). Among 77 evaluable patients, we observed seven complete responses and 32 partial responses, for an overall response rate of 51% (95% confidence interval 40% to 62%). A stabilization of disease was observed in 25% of patients while 19 patients progressed. Canadian NCI grade 3/4 toxicities were: neutropenia in 32% of patients (febrile in two), diarrhea in 10%, mucositis in 4%, and fatigue in 4%. Sensory neuropathy was mild and occurred as grade 3 in 6% of patients. ADL and IADL scores did not change significantly during treatment.
  
  
  CONCLUSIONS
  The bi-fractionated delivery of oxaliplatin plus 5-FU/leucovorin demonstrated high antitumor activity in elderly patients with advanced colorectal cancer. Splitting oxaliplatin administration might reduce incidence of severe neuropathy, although this has to be confirmed by further studies.
authors.affiliation: S. Croce Hospital, Medical Oncology Unit, Fano.
authors.forename: R
authors.initials: R
authors.lastname: Mattioli
authors.forename: C
authors.initials: C
authors.lastname: Massacesi
authors.forename: F
authors.initials: F
authors.lastname: Recchia
authors.forename: F
authors.initials: F
authors.lastname: Marcucci
authors.forename: C
authors.initials: C
authors.lastname: Cappelletti
authors.forename: L
authors.initials: L
authors.lastname: Imperatori
authors.forename: A
authors.initials: A
authors.lastname: Pilone
authors.forename: M
authors.initials: M
authors.lastname: Rocchi
authors.forename: A
authors.initials: A
authors.lastname: Cesta
authors.forename: G
authors.initials: G
authors.lastname: Laici
authors.forename: M
authors.initials: M
authors.lastname: Bonsignori
authors.forename: P
authors.initials: P
authors.lastname: Lippe
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil