PURPOSE: To determine the tolerability and efficacy of ABT-751, an oral antimitotic agent that inhibits polymerization of microtubules, in patients with advanced taxane-refractory non-small cell lung carcinoma (NSCLC). PATIENTS AND METHODS: Eligibility was limited to patients with recurrent or metastatic NSCLC who had received one to two cytotoxic chemotherapy regimens, had a performance status of zero to one, and adequate organ function. Treatment included ABT-751 200 mg daily for 21 consecutive days, followed by 7 days off drug. Objectives were to determine response rate, time to tumor progression, survival, and tolerability of ABT-751. RESULTS: All 35 enrolled patients were assessable for survival, response, and tolerability. Median time to tumor progression and overall survival were 2.1 and 8.4 months, respectively. The objective response rate was 2.9%. One patient achieved a partial response that was ongoing 567 days after initial documentation. Treatment was well tolerated; fatigue, constipation, and dehydration were the only treatment related, grade three adverse events occurring in more than one patient. Incidence of grade 3/4 hematologic and blood chemistry toxicities was acceptable, and ABT-751 was not associated with myelosuppression. CONCLUSIONS: ABT-751 associated toxicity was acceptable. The median time to progression and overall survival as demonstrated for ABT-751 were comparable to other agents considered active in this patient population and to current treatments approved for second-line NSCLC. The novel antimitotic targeting of ABT-751 in combination with the compound's acceptable nonmyelosuppressive toxicity profile and efficacy similar to agents currently in use in this setting, warrant further evaluation of this compound in combination with other cytotoxic agents in advanced NSCLC.
All Science Journal Classification (ASJC) codes
- Pulmonary and Respiratory Medicine