BACKGROUND: This study was conducted before the approval of oxaliplatin, cetuximab, and bevacizumab and was designed to evaluate a novel microtubule targeting agent, T138067, in patients with metastatic colorectal cancer (CRC) previously treated with irinotecan and 5-fluorouracil. PATIENTS AND METHODS: Patients from 3 institutions were enrolled over 4 months and treated with T138067 on days 1, 8, and 15 of a 21-day cycle. Disease evaluation was performed after 9 weeks. RESULTS: Treatment was tolerable with moderate hematologic and gastrointestinal toxicity. Neurotoxicity, an expected side effect, was minimal. Among 23 evaluable patients, there were no responses. Median time to tumor progression was 1.4 months and median survival was 9.3 months. CONCLUSION: T138067 at this dose and schedule was well tolerated by patients with CRC. However, there was no evidence of clinical activity for T138067 in 5-fluorouracil/irinotecan-refractory CRC. The long median survival likely reflects availability of other agents and/or patient selection.
BACKGROUND: This study was conducted before the approval of oxaliplatin, cetuximab, and bevacizumab and was designed to evaluate a novel microtubule targeting agent, T138067, in patients with metastatic colorectal cancer (CRC) previously treated with irinotecan and 5-fluorouracil. PATIENTS AND METHODS: Patients from 3 institutions were enrolled over 4 months and treated with T138067 on days 1, 8, and 15 of a 21-day cycle. Disease evaluation was performed after 9 weeks. RESULTS: Treatment was tolerable with moderate hematologic and gastrointestinal toxicity. Neurotoxicity, an expected side effect, was minimal. Among 23 evaluable patients, there were no responses. Median time to tumor progression was 1.4 months and median survival was 9.3 months. CONCLUSION:T138067 at this dose and schedule was well tolerated by patients with CRC. However, there was no evidence of clinical activity for T138067 in 5-fluorouracil/irinotecan-refractory CRC. The long median survival likely reflects availability of other agents and/or patient selection.
Authors: Cristina C Rohena; Nakul S Telang; Chenxiao Da; April L Risinger; James A Sikorski; Glen E Kellogg; John T Gupton; Susan L Mooberry Journal: Mol Pharmacol Date: 2015-12-11 Impact factor: 4.436
Authors: Rachel E Morgan; Sunnoo Ahn; Sandra Nzimiro; Jean Fotie; Mitch A Phelps; Jeffrey Cotrill; Adam J Yakovich; Dan L Sackett; James T Dalton; Karl A Werbovetz Journal: Chem Biol Drug Des Date: 2008-12 Impact factor: 2.817