title: A phase I/II study of trimetrexate and capecitabine in patients with advanced refractory colorectal cancer.
abstract: OBJECTIVE
  We tested the hypothesis that the combination of trimetrexate (TMTX) and capecitabine (CAP) would be active in patients with previously treated metastatic colorectal cancer (CRC). Because the optimum dose of this combination was unknown, we used a phase I/II design.
  
  
  METHODS
  In the phase I cohort, patients received 110 mg/m2 TMTX intravenously weekly x6 and CAP starting at 750 mg/m2 orally twice daily from days 2 to 15 and 23 to 36 (one cycle). Cycles were repeated every 8 weeks. The phase II doses were 110 mg/m2 TMTX and 1000 mg/m2 CAP orally twice daily.
  
  
  RESULTS
  Thirty-two patients were entered. All patients had prior 5-fluorouracil therapy and 94% had prior exposure to irinotecan. Grade 3/4 toxicities included abdominal pain in 4 patients (12.5%) and vomiting in 3 patients (9.4%). Twenty-seven patients were evaluable for response: one patient each had a complete response and a partial response for an overall response rate of 7.4%. The median time to progression was 3.3 months (95% confidence interval [CI], 1.6-3.7 months) and the median overall survival was 5.9 months (95% CI, 5.2-10.2 months).
  
  
  CONCLUSIONS
  The combination of TMTX and CAP is well tolerated. However, recent studies have shown more active regimens in the second- and third-line metastatic setting.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Khalid
authors.initials: K
authors.lastname: Matin
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Jacobs
authors.forename: Thomas
authors.initials: T
authors.lastname: Richards
authors.forename: Michael K
authors.initials: MK
authors.lastname: Wong
authors.forename: Martin
authors.initials: M
authors.lastname: Earle
authors.forename: Terry
authors.initials: T
authors.lastname: Evans
authors.forename: Monica
authors.initials: M
authors.lastname: Troetschel
authors.forename: William
authors.initials: W
authors.lastname: Ferri
authors.forename: David
authors.initials: D
authors.lastname: Friedland
authors.forename: Richard
authors.initials: R
authors.lastname: Pinkerton
authors.forename: Robert
authors.initials: R
authors.lastname: Volkin
authors.forename: Samuel
authors.initials: S
authors.lastname: Wieand
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramanathan
mesh_terms: 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 / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016597:Trimetrexate / Q000008:administration & dosage
chemical_list: D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D016597:Trimetrexate