Raltitrexed (tomudex) administration in patients failing multiple prior chemotherapy regimens in advanced colorectal cancer: a pilot study

Purpose: To evaluate efficacy of Raltitrexed, a specificthymidilate synthase inhibitor, in patients with advancedcolorectal cancer (ACC) failing multiple prior chemotherapyregimens (e.g. 5-FU+LV, CPT-11, etc). Methods: 20 patients with ACC; 13 males/7 females,median age 64 (range: 53–69), median Karnovsky PS: 80 (70–90), and sites of metastases; liver: 16, lung: 6, lymph nodes:9, peritoneal: 8 and a life expectancy of at least 3 months,were entered in the present pilot study of Raltitrexedadministration. All patients had progressed after priorchemotherapy with 5-FU+LV and subsequently CPT-11, and somehad received further infusional 5-FU. Raltitrexed wasadministered at a dose of 3 mg/m² i.v. every 21 days. Results: 3 patients obtained stable disease (SID), 15%,with tumor marker decline (CEA, CA-19.9). Time-to-progressionwas 4.8 months (2.2–7) and survival 7.4 months (6.0–7.8).Toxicity was in general not severe and consisted mainly ofmyelosuppression; neutropenia (WHO) grade 2: 45% and grade 3:22%, and anemia grade 1–2: 40%. Conclusion: Response to treatment with Raltitrexed islimited in patients with ACC failing multiple priorchemotherapy regimens, however, a limited percentage ofpatients with SD derived clinical benefit.