title: Oxaliplatin and protracted continuous 5-fluorouracil infusion in patients with pretreated advanced colorectal carcinoma.
abstract: BACKGROUND
  Both OHP and 5-FU are clinically active as single agents in the treatment of metastatic colorectal cancer (MCRC). Clinical and laboratory studies suggest a synergistic interaction between these agents. This phase II study was performed to evaluate the activity of a schedule including OHP and protracted 5-FU infusion in 5-FU-resistant MCRC.
  
  
  METHODS
  From October 1997 to January 2000, 50 patients with measurable progressive MCRC after one or more 5-FU-based regimens were treated. OHP (2-3-hour i.v. infusion) on day 1 and 5-FU (protracted i.v. infusion using elastomeric/electronic pump through a central venous catheter) on days 1-21 were administered every 3 weeks, at the following 4 dose levels: 1) OHP 100 mg/m2 + 5-FU 200 mg/m2 (21 patients); 2) OHP 100 mg/m2 + 5-FU 250 mg/m2 (3 patients); 3) OHP 130 mg/m2 + 5-FU 200 mg/m2 (10 patients); 4) OHP 130 mg/m2 + 5-FU 250 mg/m2 (6 patients).
  
  
  RESULTS
  Objective responses were 1 (2%) CR; 10 (20%) PR, for a median duration of 8 months; 23 (46%) stable diseases, for a median duration of 6 months: 16 (32%) progressions. CR + PR was higher in patients who had previously received no more than one line of chemotherapy for metastatic disease as compared with patients who had received two or more lines of therapy (33% vs. 5%, P < 0.01). The median time to progression was four months (one to nine). All dose levels (313 cycles) were well tolerated with mild toxicity. Major toxicity (grade 3 WHO) included: anaemia in 1 patient (2%), nausea and vomiting in 1 patient (2%), diarrhoea in 4 patients (8%) and stomatitis in 1 patient (2%); grade I and 2 peripheral neuropathy were encountered, respectively, in 30 (60%) and 8 (16%) patients. The median survival was 13 months (9-17), with 32 patients still alive after a median follow-up of 8 months.
  
  
  CONCLUSIONS
  This study suggests that 1) OHP plus protracted 5-FU infusion is an active combination in MCRC patients resistant to pre-treatment bolus 5-FU; 2) it has a good tolerability profile and 3) the optimum dose level is OHP 130 mg/m2 and 5-FU 250 mg/m2.
authors.affiliation: Department of Oncology and Haematology, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Martoni
authors.forename: E
authors.initials: E
authors.lastname: Mini
authors.forename: C
authors.initials: C
authors.lastname: Pinto
authors.forename: S
authors.initials: S
authors.lastname: Nobili
authors.forename: A L
authors.initials: AL
authors.lastname: Gentile
authors.forename: P
authors.initials: P
authors.lastname: Dentico
authors.forename: B
authors.initials: B
authors.lastname: Angelelli
authors.forename: S
authors.initials: S
authors.lastname: Scicolone
authors.forename: E
authors.initials: E
authors.lastname: Piana
authors.forename: T
authors.initials: T
authors.lastname: Mazzei
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D015996:Survival Rate
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil