Retrospective Analysis of S-1 Monotherapy in Patients with Metastatic Colorectal Cancer After Failure to Fluoropyrimidine and Irinotecan or to Fluoropyrimidine, Irinotecan and Oxaliplatin

Abstract

Chemotherapy with irinotecan (CPT-11) or oxaliplatin (l-OHP) in combination with infusional 5-fluorouracil (5-FU) and their cross-over as second-line therapies are standard treatments for metastatic colorectal cancer (MCRC). Molecular target agents, which are used as third-line therapies in Western countries after failure of these three drugs, have not been available in Japan. Monotherapy with S-1 [Tegafur, Oteracil potassium and 5-chloro-2,4-dihydroxypyrimidine (CDHP)] showed activity against colorectal cancer with a response rate of 35% as a first-line therapy. It is not clear whether inhibition of dihydropyrimidine dehydrogenase by CDHP can modulate the activity of 5-FU even after patients initially fail with 5-FU. This retrospective study evaluated the efficacy and safety of monotherapy with S-1 for MCRC after the failure of standard chemotherapy. The subjects of this study comprised two cohorts; the first was 27 patients with MCRC who had failed with 5-FU and CPT-11 before approval of l-OHP in Japan (cohort 1), and the second was 23 patients who had failed with 5-FU, CPT-11 and l-OHP (cohort 2). S-1 was given orally twice daily (80 mg m(2)/day) for 28 days followed by a 14-day rest. In cohorts 1 and 2, the response rates were 7% and 0%, and the median progression-free survivals were 2.8 and 2.7 months, and overall survivals after initiation of S-1 were 10.5 and 4.7 months, respectively. The common grade 3 and 4 adverse events in cohorts 1 and 2 were diarrhea 15% and 13%, anorexia 11% and 17% and anemia 26% and 30%, respectively. S-1 monotherapy did not show promising activity against MCRC after the failures with 5-FU, CPT-11 and l-OHP.