A phase I trial of PTK787/ZK222584 in combination with pemetrexed and cisplatin in patients with advanced solid tumors.

Angiogenesis is recognized as an important biological process that allows growth of a tumor beyond an initial small size. PTK787/ZK222584, a potent orally active angiogenesis inhibitor capable of inhibiting all known isoforms of Vascular Endothelial Growth Factor (VEGF) receptor, belongs to the class of aminophthalazines. This study investigated a combination of chemotherapy (Cisplatin and Pemetrexed) with PTK787/ZK222584. Eight patients were enrolled but PTK787/ZK222584 dose could not be escalated as planned because of dose limiting toxicities (DLTs) observed on the first dose level. Limited pharmacokinetic profiling of PTK787/ZK222584 revealed no evidence of drug-drug interactions. No responses were seen for this combination. This study was closed secondary to toxicity and lack of efficacy of the designed regimen.