title: Oxaliplatin and raltitrexed combined with leucovorin-modulated 5-fluorouracil i.v. bolus every two weeks: a dose finding study in advanced previously treated colorectal carcinoma. Southern Italy Cooperative Oncology Group.
abstract: OBJECTIVE
  To determine the maximum tolerated dose of oxaliplatin (L-OHP) given as a two-hour infusion followed by raltitrexed (Tomudex [TOM]) administered as a 15-min infusion on day 1, and bolus 5-fluorouracil (5-FU) modulated by a fixed dose of levo-folinic acid (LFA) 250 mg/m2 on day 2, recycling every two weeks, and to have preliminary evidence of activity of this combination in pretreated advanced colorectal cancer patients.
  
  
  METHODS
  Fifty-two patients with advanced colorectal carcinoma previously treated with one (25 cases) or two or more lines of chemotherapy, including irinotecan (26 cases), and/or modulated 5-FU (40 cases) entered this study. Starting doses of L-OHP, TOM, and 5-FU were 85, 2.5 and 750 mg/m2, respectively.
  
  
  RESULTS
  Seven dose levels were tested. Neutropenia was the main dose limiting toxicity of the dose escalation (8 of 13 cases). The recommended doses were 130 mg/m2 of L-OHP, and 3.0 mg/m2 of TOM on day 1, followed by 250 mg/m2 of LFA, and 1050 mg/m2 of 5-FU on day 2, every two weeks. Severe diarrhoea and stomatitis were rarely reported. Most patients complained of mild peripheral sensitive aeurotoxicity, which was related to the cumulative dose of L-OHP. Twelve patients were considered as having a major responses (one complete), and an additional eight patients showed a minor response; the median time to treatment failure was twenty-four weeks.
  
  
  CONCLUSIONS
  With this regimen it is possible to give full doses of all three cytotoxic drugs every two weeks. Its activity and its manageable toxicity profile deserve further evaluation in pretreated advanced colorectal cancer patients.
authors.affiliation: Medical Oncology A, National Tumour Institute, Naples, Italy. pcomella@sirio-oncology.it
authors.forename: P
authors.initials: P
authors.lastname: Comella
authors.forename: F
authors.initials: F
authors.lastname: De Vita
authors.forename: L
authors.initials: L
authors.lastname: De Lucia
authors.forename: R
authors.initials: R
authors.lastname: Casaretti
authors.forename: A
authors.initials: A
authors.lastname: Avallone
authors.forename: M
authors.initials: M
authors.lastname: Orditura
authors.forename: F
authors.initials: F
authors.lastname: Rivellini
authors.forename: S
authors.initials: S
authors.lastname: Palmeri
authors.forename: G
authors.initials: G
authors.lastname: Catalano
authors.forename: G
authors.initials: G
authors.lastname: Comella
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D011799:Quinazolines; D013876:Thiophenes; D000077150:Oxaliplatin; C068874:raltitrexed; D002955:Leucovorin; D005472:Fluorouracil