A phase I study of raltitrexed (Tomudex) combined with carmofur in metastatic colorectal cancer

Objectives: The aim of the study was to define the maximum tolerated dose ( MTD) of the combination of raltitrexed plus carmofur, and to evaluate the t olerability and efficacy of this combination in metastatic colorectal cance r. Methods: Twenty-eight patients (23 receiving first-line therapy, 5 recei ving second-line therapy) entered the study; 16 were chemonaive. Raltitrexe d (Tomudex) 1.5-3.0 mg/m(2) was given as a 15- to 30-min intravenous infusi on on day 1 of a 21-day cycle followed by carmofur 300-400 mg/m(2) orally 3 times daily on days 2-14. Therapy was given until disease progression or d ose-limiting toxicity (DLT) occurred. Results: A total of 170 cycles of the rapy were administered. The MTD was reached at the raltitrexed dose of 3.0 mg/m(2) and the carmofur dose of 400 mg/m(2). DLTs included grade 3-4 diarr hea, fatigue, anorexia, mucositis, anemia, thrombocytopenia, neutropenia, n eurological symptoms and febrile neutropenia. Eleven of the 22 evaluable fi rst-line patients achieved a partial response (response rate 50%, 95% confi dence interval 29-71%), 8 had stable disease and 3 had disease progression. One of the 5 patients who received second-line therapy responded. Conclusi ons:The recommended dose of this combination therapy for further evaluation is raltitrexed 3.0 mg/m(2) plus carmofur 300 mg/m(2). This combination has unique but manageable toxicity and promising efficacy in metastatic colore ctal cancer. Copyright (C) 2001 S. Karger AG, Basel.