Neha Vapiwala, MD The Abramson Cancer Center of the University of Pennsylvania
Vatalanib (PTK 787/ZK 222584)
Vatalanib is an oral drug that selectively inhibits all three types of VEGFR, as well as platelet-derived growth factor receptor (PDGFR) and c-KIT. (Note: c-KIT is a tyrosine kinase receptor pathway that is important for tumor growth and progression in several cancers, including gastrointestinal stromal tumor, acute myeloid leukemia, small cell lung carcinoma, and Ewing sarcoma.)
Phase I trials found maximally tolerated dose (MTD) of 750 mg twice daily and dose-limiting toxicity (DLT) of sudden lightheadedness.
CONFIRM I is a multinational, randomized phase III study of over 1,000 patients with previously untreated metastatic CRC, testing FOLFOX (a combination of oxaliplatin, fluorouracil (5-FU), and leucovorin) with either PTK 787 or placebo.
Preliminary results presented at ASCO 2005 show no difference to date in either RR or PFS.
CONFIRM II is also a multinational, randomized phase III trial evaluating PTK787 in patients with metastatic CRC who are refractory to irinotecan/5-FU therapy.
AZD 2171 is an oral drug that potently inhibits all three types of VEGFR as well as PDGFR.
No MTD was reached in phase I studies, and the most common toxicities seen were fatigue, nausea, and vomiting.
Several clinical trials of AZD 2171 are currently accruing for the following diseases: liver metastases, acute myelogenous leukemia, and prostate cancer.
Preliminary results on tumor response appear promising.
GW 786034 is an oral drug that selectively inhibits all three types of VEGFR.
Currently in phase I dose escalation trials, with 800 mg/daily as a potential dose for phase II trials.
Most common side effects were hypertension, diarrhea, nausea, vomiting, and fatigue.
Minor responses seen in renal cell carcinoma and leiomyosarcoma.
SU 11248 is an oral drug that inhibits VEGFR-2, PDGFR, KIT, and FLT3.
Phase I trials found DLT of fatigue, and recommended a phase II dose of 50 mg daily x 4 weeks with a 2-week break.
Two phase II trials are studying the use of sunitinib as second-line therapy for metastatic renal cell carcinoma.
Overall response rate of ~40% in both studies, almost entirely partial responses.
Stable disease for > 3 months in ~25% of patients.