title: Capecitabine and oxaliplatin in advanced colorectal cancer: a dose-finding study.
abstract: OBJECTIVE
  Capecitabine and oxaliplatin are both active anticancer agents in the treatment of patients with advanced colorectal cancer (ACRC). The aim of this dose-finding trial was to determine the maximum-tolerated dose (MTD), the dose-limiting toxicities (DLTs) and the activity of the combination in patients with advanced colorectal cancer.
  
  
  METHODS
  Twenty-five chemotherapy-pretreated patients received the combination of capecitabine and oxaliplatin. Capecitabine was administered orally twice a day continuously for 14 days in doses ranging from 1,650 to 2,500 mg/m2/d, and oxaliplatin was administered as a two-hour infusion on day 1 using dose, ranges from 100 to 130 mg/m2 repeated every three weeks.
  
  
  RESULTS
  Twenty-five patients were assessable for toxicity, and DLTs were diarrhea (grade > or = 3: 27%) and stomatitis (grade > or = 3: 9%) at dose level VI. Dose level V (capecitabine 2500 mg/m2 and oxaliplatin 120 mg/m2) was found to be the MTD. Hematological toxicity was minimal, overall neurotoxicity (grade 1-4) was 27% with 1% grade 3-4. A global response rate was 17% (95% confidence interval (95% CI): 2%-32%) and the median overall survival was 12 months.
  
  
  CONCLUSIONS
  The recommended dose for further phase II studies is capecitabine 2,500 mg/m2/d with intermittent schedule and oxaliplatin 120 mg/m2 every three weeks. The toxicities were mainly gastrointestinal: diarrhea, stomatitis and vomiting. This combination should be studied in phase II trials in advanced colorectal.
authors.affiliation: Department of Medical Oncology A, Regina Elena Cancer Institute, Rome, Italy. massimozeuli@tiscalinet.it
authors.forename: M
authors.initials: M
authors.lastname: Zeuli
authors.forename: E
authors.initials: E
authors.lastname: Di Costanzo
authors.forename: A
authors.initials: A
authors.lastname: Sdrobolini
authors.forename: S
authors.initials: S
authors.lastname: Gasperoni
authors.forename: F P
authors.initials: FP
authors.lastname: Paoloni
authors.forename: A
authors.initials: A
authors.lastname: Carpi
authors.forename: L
authors.initials: L
authors.lastname: Moscetti
authors.forename: R
authors.initials: R
authors.lastname: Cherubini
authors.forename: F
authors.initials: F
authors.lastname: Cognetti
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D012449:Safety; D015996:Survival Rate
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil