A randomized phase II study of raltitrexed and gef

Authors: José María Viéitez Manuel Valladares Ignacio Peláez Luis de Sande González Jesús GarcíaFoncillas José Luis GarcíaLópez Carlos GarcíaGirón Margarita Reboredo Humberto Bovio Angel Jiménez Lacave

Publish Date: 2010/03/06

Volume: 29, Issue: 5, Pages: 1038-1044

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Abstract

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 iv every 21 days plus either daily gefitinib 250 mg po 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 79 3 patients CI 95 166–2138 versus 53 2 patients CI 064–1775 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

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