Drug Detail

Information about Sutent

Generic Name	Sunitinib
IND	SU11248
Brand Name (US)	Sutent
Manufacturer	Pfizer
Drug Type	Tyrosine Kinase Inhibitor
Delivery	Oral
Approval Status	Approved for GIST (2nd line)
Indications
Overall Strategy	KIT Protein Based
Strategy	Block KIT
Drug Category	KIT/PDGFRA inhibitor

The United States Food and Drug Administration (FDA) announced Jan. 26 2006, that it has approved Sutent (sunitinib) for patients with GISTs that had stopped responding to Gleevec or that were unable to tolerate Gleevec. It is also approved for advanced kidney cancer and for pancreatic neuroendocrine tumors (pNET).

Sutent is also approved in a number of countries outside of the United States.

Sutent® is known by several different names:

* Sutent®, the brand name
* Sunitinib malate, the generic name
* SU11248 (sometimes written as SU011248) in clinical trials

Sutent is a pill that is taken once daily. The usual dosage is 50 mg per day. It is given daily for four weeks, before a two week rest period. This cycle is then repeated as long as the patient continues to show benefit. A phase II trial examining the effects of giving a lower dose of Sutent (37.5 mg) on a continuous basis concluded that Sutent appeared to be a safe and potentially effective dosing strategy for GIST patients. Although significant caution should be applied when comparing two different trial results, the median progression-free survival time of continuous dosing was 34 weeks (7.8 months). This compares favorably with the standard dosing schedule which produced a median progression-free survival time of 6.3 months. For GIST and Renal Cell Carcinoma, the FDA approved dosage remains (2011) at 50 mg on a 4/2 schedule. Interestingly, a later approval (2011) for pancreatic neuroendocrine tumors (pNET), is for the continuous dosing schedule at 37.5 mg.

Sutent is a tyrosine kinase inhibitor that is similar to Gleevec in some ways. Both drugs inhibit the KIT protein (mutated in 80-85% of GISTs) and the PDGFRα protein (mutated in 5-7% of GISTs). Inhibition of these proteins provides a direct anti-tumor effect when the target protein (KIT or PDGFRα) is mutated. In addition, some tumors that don't have KIT or PDGFRα mutations (called "wild-type" GISTs) might still provide a growth/survival signal through KIT activation and might still benefit from KIT inhibition (either by Gleevec or by Sutent).

Both Sutent and Gleevec also provide an antiangiogenic effect through inhibition of PDGFRβ. PDGFRβ is involved in the recruitment of pericytes, which are needed to form new blood vessels to feed the tumors.

In addition to inhibiting these three proteins, Sutent provides an additional antiangiogenic effect that Gleevec does not; Sutent inhibits the "VEGF" receptors. VEGF is one of the most promising of the antiangiogenesis targets. For detailed information about angiogenesis visit the website of The Angiogenesis Foundation.
Caution: Proper monitoring is required for patients on Sutent. This includes, but is not limited to, monitoring thyroid function, blood pressure, blood counts and monitoring for heart problems. See the Sutent prescribing information and the links below.

A possible drug interaction with bisphophonates (drugs used to treat osteoporosis and bone metastastes) has been reported.