Phase III randomized trial of sunitinib malate (SU11248) versus interferon-alpha (IFN-alpha) as first-line systemic therapy for patients with metastatic renal cell carcinoma (mRCC).
Reviewer: John P. Plastaras, MD, PhD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 5, 2006
Presenter: Robert J. Motzer Presenter's Affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY Type of Session: Plenary
Clear cell renal cell carcinoma (RCC) is characterized by mutation or silencing of the VHL gene, which in turn leads to increased activity of hypoxia inducible factor (HIF). This in turn leads to over-expression of receptors and ligands involved in angiogenesis
Sorafenib, a multikinase inhibitor that targets Raf kinase and angiogenesis receptor tyrosine kinases, doubled progression free survival (PFS) when used as second-line treatment, which lead to FDA approval in 12/2005
Sunitinib (SU11248) is an anti-angiogenic small molecule, multikinase inhibitor that targets VEGFR-1, 2, and 3, PDGFR-alpha, beta, Ret, Flt3 and Kit
Two multicenter Phase II trials of sunitinib used as 2nd line monotherapy showed a 39-40% response rate
The FDA approved sunitinib for use as first line therapy in mRCC and second line therapy for GI stromal tumors in January 2006
This is a randomized trial that tested sunitinib vs. IFN-alpha in first line treatment of mRCC
Materials and Methods
Phase III study design:
International, multicenter, randomized
- 750 patients with mRCC accrued 8/2004-10/2005 were randomized 1:1 to:
IFN-alpha (n=350) vs. sunitinib (n=350)
IFN-alpha administration: 3 million units (MU) s.q. three times weekly x 1 wk, that was dose escalated to 6 MU x 1 wk, then 9 MU
Sunitinib administration: 50 mg daily for 4 wks, then 2 wks off. Cycles repeated.
Criteria: mRCC patients with measurable disease, no prior systemic treatment
Nov 4, 2011 - Use of zidovudine and interferon alfa with chemotherapy (combined first-line therapy) prolongs survival in patients with adult T-cell leukemia/lymphoma, according to a study published online Oct. 31 in the Journal of Clinical Oncology.