Phase II study of first-line LY231514 (multi-targeted antifolate) in patients with locally advanced or metastatic colorectal cancer: An NCIC ClinicalTrials Group study

Background: Metastatic colon cancer is difficult to treat with treatment be ing palliative and with little effect on survival. This trial has evaluated the effects of LY231514 (Multitargeted antifolate (MTA)) given to previous ly untreated patients with recurrent or metastatic colorectal carcinoma. Patients and methods: All patients were required to have a histological dia gnosis of colorectal adenocarcinoma with measurable disease and no prior ch emotherapy for metastatic disease. Patients had to have had performance sta tus of 0-2, pretreatment absolute granulocyte count of greater than or equa l to 1.5 x 10(9)/l and a platelet count of greater than or equal to 150 x 1 0(9)l. Patients received MTA at a dose of 600 mg/m(2) by 10 minute infusion on day 1 repeated every 21 days. After the first 9 patients, this dose was reduced down to 500 mg/m(2) every 21 days because of toxicity. Doses of MT A were modified depending on nadir counts. Results: Thirty-two eligible patients were enrolled and twenty-nine were ev aluable for response. Three patients did not have repeat radiological testi ng to determine response because they went off study after only one cycle o f treatment due to toxicity. In the 29 evaluable patients, there was 1 comp lete response, 4 partial responses and 14 patients with stable disease. Res ponse 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/m(2). Medi an time to progression for all eligible patients was 3.3 months. The most c ommon toxicities experienced were mild to moderate fever, lethargy, anorexi a, nausea, vomiting, stomatitis, abdominal pain, diarrhea, and skin rash. T here was one death due to sepsis. Conclusion: Single-agent MTA at 500 mg/m(2) given every three weeks has mod est activity in metastatic colorectal carcinoma.