Phase 2 study of cryptophycin 52 (LY355703) in patients previously treated with platinum based chemotherapy for advanced non-small cell lung cancer

Background: Cryptophycin 52 is a novel antitubulin drug with in vitro and in vivo activity in non-small cell lung cancer. Based upon promising Phase 1 data, a multicenter trial was performed to evaluate the drug in previously treated non-small cell lung cancer (NSCLC). Methods: Patients with Stage IIIb (pleural effusion) or Stage IV NSCLC and performance status 0-1 with adequate organ function who had received at least one and no more than two prior chemotherapy regimens (one of which must have contained a platinum agent) were eligible. Cryptophycin 52 was administered at a dose of 1.5 mg/m² day 1 and 8 every 3 weeks. Patients were reassessed every two cycles. Results: Twenty-six patients were enrolled of whom 25 are evaluable for toxicity and response. There were no responders, toxicity was predominantly neurologic in the form of peripheral neuropathy and constipation. After the first 12 patients were enrolled, the dose was lowered to 1.125 mg/m² day 1 and 8. Toxicity was substantially reduced with this maneuver. Median survival was 4.1 months. The median number of cycles was two, however ten patients received four or more courses of therapy. Conclusion: Cryptophycin 52 failed to produce measurable responses utilizing this schedule. In 40% of patients there was evidence of disease stabilization. Toxicity at 1.5 mg/m² was unacceptable. Since activity and toxicity may be dose and schedule dependent, other schedules of cryptophycin 52 should be considered.