Phase I trial of oral CP-547,632 (VEGFR2) in combination with paclitaxel (P) and carboplatin (C) in advanced non-small cell lung cancer (NSCLC)

3014 Background: Overexpression of vascular endothelial growth factor (VEGF) portends a poor outcome in NSCLC. Tumor angiogenesis may be mediated by VEGF signaling through the VEGF receptor-2 (VEGFR-2). CP-547, 632 is a potent, selective inhibitor of VEGFR-2 tyrosine kinase activity. The addition of CP-547,632 to chemotherapy may enhance clinical benefit. Methods: This study examined the safety and PK of escalating oral QD doses of CP-547,632 given in combination with P(225mg/m2) and C( AUC = 6) administered in 21 day cycles to chemotherapy naive patients with PS 0–1 stage IIIb or IV NSCLC with or without stable brain mets and PS 0–1. Anti-tumor activity was also assessed. Results: 29 patients received a median of 2+ cycles (range 1–13) of study therapy. In this setting, the maximum tolerable dose for CP-547,632 was 200 mg/d. Preliminary safety data reveal the most common treatment emergent adverse events to be diarrhea, fatigue, nausea, neuropathy, emesis, alopecia, dyspnea and arthralgia/myalgia. CP-547...