Efficacy and toxicity of the angiogenesis inhibitor SU5416 as a single agent in patients with advanced renal cell carcinoma, melanoma, and soft tissue sarcoma.
BACKGROUND
Vascular endothelial growth factor (VEGF) is a key regulator in angiogenesis. Preclinical and clinical data support the role of VEGF and angiogenesis in renal cell carcinoma (RCC), melanoma (M), and soft tissue sarcoma (STS). The tyrosine kinase inhibitor SU5416 is a potent inhibitor of the VEGF receptors 1 and 2.


METHODS
We investigated 145 mg/m(2) SU5416 twice weekly in patients with advanced or metastatic RCC, M, and STS. The primary objectives were efficacy and safety. Disease assessments were performed after 4 and 8 weeks of treatment and every 2 months thereafter. Documented stable disease (SD) lasting for > or =3 months was considered an antitumor response.


RESULTS
A group of 29 patients was entered in the RCC trial, 20 patients in the M trial, and 31 patients in the STS trial. Response was observed in 6 (1 minor response and 5 SDs) of 24 evaluable patients (25%) in the RCC group, 6 (1 minor response and 5 SDs) of 26 patients (23%) in the STS group, and none of the patients in the M group. Progression-free survival ranged from 7 to 252 days (median 59 days) in the RCC group, from 7 to 260 days (median 60 days) in the STS group, and from 14 to 139 days (median 41 days) in the M group. Toxicities observed were those reported previously for SU5416.


CONCLUSIONS
SU5416 single agent is well tolerated. The antitumor response was low in patients with RCC and STS, whereas no responses were seen in patients with M.
Department of Medical Oncology, Vrije Universiteit Medical Center, 1081 HV Amsterdam, the Netherlands.
Bart C
BC
Kuenen
Jose
J
Tabernero
Jose
J
Baselga
Franco
F
Cavalli
Elisabeth
E
Pfanner
Pier Franco
PF
Conte
Siegfried
S
Seeber
Srinivasan
S
Madhusudan
Gael
G
Deplanque
Holgen
H
Huisman
Paul
P
Scigalla
Klaas
K
Hoekman
Adrian L
AL
Harris
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy; D018572:Disease-Free Survival; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000627:therapeutic use*; D012509:Sarcoma / Q000188:drug therapy / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D004791:Enzyme Inhibitors; D007211:Indoles; D011758:Pyrroles; C116890:Semaxinib; D011505:Protein-Tyrosine Kinases