Description:
<jats:p> e13550 </jats:p><jats:p> Background: Ix is a semisynthetic epiothilone analog which inhibits mitosis through microtubule stabilization, with activity in multiple tumor types. Weekly dosing may have less toxicity. B improves survival in combination with carboplatin and paclitaxel for previously untreated non-squamous NSCLC. The use of B in the salvage setting has not been extensively studied. Methods: Non-randomized, open-label, single arm phase II trial of B, 10 mg/kg iv every 2 weeks and Ix, 20 mg/m2 iv weekly for 3 out of 4 weeks. An initial lead-in phase of 6 patients (pts) treated with B and Ix (16 mg/m2 iv weekly for 3 out of 4 weeks) was planned. Pts with advanced non-squamous NSCLC progressive after 1 or 2 lines of therapy are eligible, prior erlotinib is allowed, ECOG 0-1. Prior B is allowed. Pts are treated for a maximum of 6 28-day cycles, with staging every 2 cycles. Pts with response or stable disease may continue on maintenance B for up to 1 year. Primary endpoint is progression free survival, with secondary endpoints ORR, OS, toxicity, and correlative studies to assess potential predictors of response. Correlative studies include evaluations of tumor and plasma levels of VEGF, PDGF, sICAM, bFGF, and IL-8, with hypothesis that lower levels of tumor or plasma levels will correlate with improved outcomes. VEGF and IL-8 polymorphisms will be measured, as will tumor expression of Aurora B, survivin, Ki-67, hyperphosphorylation of BCL2, and overexpression of Tau. Total accrual goal is 46 pts. Results: To date, the first 6 pts for the run-in phase have been accrued. 2 pts required dose reduction in the first 2 cycles (Gr 2 thrombocytopenia, Gr 3 ALT elevation; 1 each). Max treatment cycles: 9 (Range, 2-9). 2 pts had disease progression after 2 cycles and were discontinued from study. Toxicity in the first 2 cycles is primarily hematologic, with related Gr 2 toxicity of thrombocytopenia, anemia, lymphopenia (1 each). Gr 3 lymphopenia occurred in 2 pts. Gr 3 hyperglycemia occurred in 2 pts, attributed to steroid premeds. Conclusions: With 2 pts requiring dose reduction with the run-in dose, Ix will not be increased as previously planned and the ongoing dose for the phase II study will be 16 mg/m2. Accrual to the phase II portion will continue. </jats:p>