title: A phase II study of Tomudex alternated with methotrexate, 5-fluorouracil, leucovorin in first-line chemotherapy of metastatic colorectal cancer.
abstract: OBJECTIVE
  This multicenter phase II study was designed to assess the efficacy of the alternating schedule of tomudex with methotrexate (MTX)/5-fluorouracil (5-FU)/leucovorin (LV) in first-line chemotherapy for metastatic colorectal cancer.
  
  
  METHODS
  Patients with histologically proven metastatic colorectal cancer and at least one bidimensionally measurable lesion, aged 18-70, with performance status < or = 2, normal baseline biological values, and no prior chemotherapy, were selected. Treatment was tomudex 3 mg/m2 and, after two weeks, MTX, 200 mg/m2 by 30' infusion after hydration with 1500 ml saline solution, followed on day 2 by 5-FU, 600 mg/m2 and leucovorin, orally, 15 mg for six times every 6 hours, beginning 24 hours after MTX. Cycles were repeated every four weeks. Tumor response assessment was performed after three cycles.
  
  
  RESULTS
  Thirty-four patients were enrolled in this study, of whom twenty-four had liver metastases, nine local relapse, five lymph node involvement, four lung metastases, and three peritoneal carcinomatosis. Four patients achieved objective responses (one complete and three partial), for an overall response rate of 12% (95% CI: 0%-22%). Twelve patients had stable disease and 18 progressed on therapy. Median survival for all patients was 13 months. Two patients experienced grade 3 WHO neutropenia while hepatotoxicity was reported in 13 patients (6 grade 1, 3 grade 2, 3 grade 3, 1 grade 4), suggesting that this combination could increase hepatic toxicity in comparison to tomudex or MTX/5-FU alone.
  
  
  CONCLUSIONS
  Our results suggest that this regimen does not warrant further investigation in advanced colorectal cancer patients, at least not with this schedule and doses.
authors.affiliation: Unità Operativa di Oncologia Medica, Azienda Ospedaliera Ospedale S. Salvatore, Pesaro, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cascinu
authors.forename: R R
authors.initials: RR
authors.lastname: Silva
authors.forename: R
authors.initials: R
authors.lastname: Labianca
authors.forename: S
authors.initials: S
authors.lastname: Barni
authors.forename: R
authors.initials: R
authors.lastname: Mattioli
authors.forename: G
authors.initials: G
authors.lastname: Martignoni
authors.forename: L
authors.initials: L
authors.lastname: Frontini
authors.forename: G
authors.initials: G
authors.lastname: Gasparini
authors.forename: V
authors.initials: V
authors.lastname: Catalano
authors.forename: A M
authors.initials: AM
authors.lastname: Baldelli
authors.forename: L
authors.initials: L
authors.lastname: Giuliodori
authors.forename: R
authors.initials: R
authors.lastname: Agostinelli
authors.forename: G
authors.initials: G
authors.lastname: Catalano
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008207:Lymphatic Metastasis; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage; D015996:Survival Rate; D013876:Thiophenes / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D011799:Quinazolines; D013876:Thiophenes; C068874:raltitrexed; D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate