title: Phase II study of first-line LY231514 (multi-targeted antifolate) in patients with locally advanced or metastatic colorectal cancer: an NCIC Clinical Trials Group study.
abstract: BACKGROUND
  Metastatic colon cancer is difficult to treat with treatment being palliative and with little effect on survival. This trial has evaluated the effects of LY231514 (Multitargeted antifolate (MTA)) given to previously untreated patients with recurrent or metastatic colorectal carcinoma.
  
  
  METHODS
  All patients were required to have a histological diagnosis of colorectal adenocarcinoma with measurable disease and no prior chemotherapy for metastatic disease. Patients had to have had performance status of 0-2, pretreatment absolute granulocyte count of > or = 1.5 x 10(9)/l and a platelet count of > or = 150 x 10(9)l. Patients received MTA at a dose of 600 mg/m2 by 10 minute infusion on day 1 repeated every 21 days. After the first 9 patients, this dose was reduced down to 500 mg/m2 every 21 days because of toxicity. Doses of MTA were modified depending on nadir counts.
  
  
  RESULTS
  Thirty-two eligible patients were enrolled and twenty-nine were evaluable for response. Three patients did not have repeat radiological testing to determine response because they went off study after only one cycle of treatment due to toxicity. In the 29 evaluable patients, there was 1 complete response, 4 partial responses and 14 patients with stable disease. Response rate was 17.2% (95% confidence intervals: 5.8%-35.8%). All responses occurred in the patients receiving a starting dose of MTA 500 mg/m2. Median time to progression for all eligible patients was 3.3 months. The most common toxicities experienced were mild to moderate fever, lethargy, anorexia, nausea, vomiting, stomatitis, abdominal pain, diarrhea, and skin rash. There was one death due to sepsis.
  
  
  CONCLUSIONS
  Single-agent MTA at 500 mg/m2 given every three weeks has modest activity in metastatic colorectal carcinoma.
authors.affiliation: Ottawa Regional Cancer Centre, Ontario, Canada. ccripps@cancercare.on.ca
authors.forename: C
authors.initials: C
authors.lastname: Cripps
authors.forename: M
authors.initials: M
authors.lastname: Burnell
authors.forename: J
authors.initials: J
authors.lastname: Jolivet
authors.forename: G
authors.initials: G
authors.lastname: Batist
authors.forename: W
authors.initials: W
authors.lastname: Lofters
authors.forename: J
authors.initials: J
authors.lastname: Dancey
authors.forename: J
authors.initials: J
authors.lastname: Iglesias
authors.forename: B
authors.initials: B
authors.lastname: Fisher
authors.forename: E A
authors.initials: EA
authors.lastname: Eisenhauer
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D010166:Palliative Care; D000068437:Pemetrexed; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D013940:Thymidylate Synthase