title: Raltitrexed and mitomycin-C as third-line chemotherapy for colorectal cancer after combination regimens including 5-fluorouracil, irinotecan and oxaliplatin: a phase II study.
abstract: BACKGROUND
  To investigate the therapeutic value and safety of a third-line treatment with raltitrexed and mitomycin-C (MMC) in patients with advanced colorectal cancer (ACC) pretreated with combination regimens including 5-fluorouracil (5-FU), irinotecan (CPT-11) and oxaliplatin (L-OHP).
  
  
  METHODS
  A total of 21 patients (PS 1/2, 19/2; M/F 15/6; median age = 73) with ACC, all of whom had developed progressive disease while receiving or within 6 months of discontinuing two sequential chemotherapy lines with 5-FU, CPT-11 and L-OHP, were accrued in this study. At the time of their relapse, cytotoxic chemotherapy, consisting of intravenous raltitrexed 3 mg/m2 plus MMC 6 mg/m2 on therapeutic day 1, was initiated. Treatment courses were repeated every 4 weeks for a total of six courses unless there was prior evidence of progressive disease, unacceptable toxicity or patient refusal occurred.
  
  
  RESULTS
  All the patients were assessable for toxicity and 16 for response evaluation, having completed at least two courses of chemotherapy. The overall response rate was 0%. Seven patients (33.6%) had a stable disease and nine patients (43%) progressed. The median time to progression was 2.3 months (95% CI: 1.65-2.95%) and median overall survival (OS) 5 months (95% CI: 2.52-7.48%). No toxic deaths occurred. Third-line treatment tolerance was generally mild to moderate and easy to treat. WHO grade 3/4 anemia, neutro- and thrombocytopenia occurred in 9.5%, 4.7% and 4.7% of the patients, respectively. However, these toxicities did not have a significant impact on global quality of life.
  
  
  CONCLUSIONS
  Our data suggest that the association of raltitrexed and MMC in patients with ACC pretreated with combination regimens including 5-FU, CPT-11 and L-OHP is feasible and could contribute to increase patients' OS time. Further evaluation of this regimen seems to be warranted.
authors.affiliation: Medical Oncology Unit, S. Carlo Hospital, Potenza, Italy. rosatiger@yahoo.com
authors.forename: Gerardo
authors.initials: G
authors.lastname: Rosati
authors.forename: Antonio
authors.initials: A
authors.lastname: Rossi
authors.forename: Domenico
authors.initials: D
authors.lastname: Germano
authors.forename: Giorgio
authors.initials: G
authors.lastname: Reggiardo
authors.forename: Luigi
authors.initials: L
authors.lastname: Manzione
mesh_terms: 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*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011446:Prospective Studies; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D009944:Organoplatinum Compounds; D011799:Quinazolines; D013876:Thiophenes; D000077150:Oxaliplatin; D016685:Mitomycin; D000077146:Irinotecan; C068874:raltitrexed; D005472:Fluorouracil; D002166:Camptothecin