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.
Sharma
Sunil
S
Nevada Cancer Institute, 1, Breakthrough Way, Las Vegas, NV, 89144, USA. ssharma@nvcancer.org
Freeman
Burgess
B
Turner
Jeanette
J
Symanowski
James
J
Manno
Phillip
P
Berg
William
W
Vogelzang
Nicholas
N
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005971:Glutamates / Q000008:administration & dosage* / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D000068437:Pemetrexed; D010793:Phthalazines / Q000008:administration & dosage* / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects
D020533:Angiogenesis Inhibitors; D005971:Glutamates; D010793:Phthalazines; D011725:Pyridines; D000068437:Pemetrexed; C404768:vatalanib; D006147:Guanine; D002945:Cisplatin