A randomized phase II study of raltitrexed and gefitinib versus raltitrexed alone as second line chemotherapy in patients with colorectal cancer. (1839IL/0143)

Purpose To determine the efficacy of the addition of gefitinib to raltitrexed in patients with colorectal cancer (CRC) that have progressed after first line chemotherapy. The study also sought to explore the safety of the combination and to investigate biomarkers predictive outcome. Methods A total of 76 patients were randomized to raltitrexed (3 mg/m² i.v.) every 21 days plus either daily gefitinib (250 mg p.o.) or placebo. The primary endpoint of the study was progression free survival (PFS). Tumor tissues were collected to determine the expression of EGFR, pEGFR, pMAPK, and pAkt. Results Both groups were well balanced with regard to prognostic factors. Treatment was well tolerated with no increased in toxicity except diarrhea and skin rash in the combination group. There were no differences in PFS between the combination arm [63 days (95% CI: 57–84)] compared to the raltitrexed alone arm [72 days (95% CI: 59–132)], or overall survival 361 days (95% CI: 283–533 days) versus 291 days (95% CI: 255–539 days) respectively. The objective response rate was 7.9% (3 patients) (CI 95%: 1,66–21,38) versus 5.3% (2 patients) (CI 0,64–17,75), respectively. The biomarker studies were not conclusive. Conclusion The combination of raltitrexed and gefitinib was well tolerated although was not associated with improved progression free survival in patients with refractory CRC.