The Food & Drug Administration recently approved sunitinib (Sutent, Pfizer) for the treatment of gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib (Gleevec, Novartis). Sunitinib was also granted accelerated approval for the treatment of metastatic renal cell carcinoma (MRCC). This is the first time that the agency has approved an oncology drug for the treatment of two indications simultaneously.

"Sunitinib represents a major advance in the treatment of MRCC; traditional immunologic therapies were poorly tolerated and minimally effective," said Thomas Hutson, D.O., Pharm.D., director of genitourinary medical oncology at the Baylor Sammons Cancer Center in Dallas.

George Demetri, M.D., Quick Family Senior Investigator at the Dana-Farber Cancer Institute, Boston, noted that sunitinib inhibits multiple receptor tyrosine kinases (RTK), some of which are implicated in tumor growth, cancer metastases, and angiogenesis. He said sunitinib inhibits a broader spectrum of RTKs compared with imatinib, which explains why it was approved for two such disparate indications simultaneously.

Demetri and Hutson were pleased to report that sunitinib was fairly well tolerated in clinical studies. Hutson said hypertension was among the adverse effects he has seen most often in his clinical practice. Pfizer recommends that patients be monitored for hypertension and treated as necessary. Hutson has also seen gastrointestinal events (nausea and diarrhea) and dermatologic events (a rash on the face or body, skin discoloration, or hand/foot syndrome, which involves callus formation or blistering on the hands and/or feet).

Sunitinib's side effects are easily traceable to its mechanism of action, said Demetri. The neurotrophic-factor receptor RET, for example, is important in thyroid physiology, so hypothyroidism has been observed after several months of sunitinib therapy. Pfizer advises that patients with symptoms suggestive of hypothyroidism have their thyroid function monitored and be treated accordingly.

Anemia and neutropenia may be associated with sunitinib use, Hutson said. Pfizer suggests that those receiving sunitinib be monitored regularly for myelosuppression and recommends that complete blood counts (CBCs) with platelet count and serum chemistries, including phosphate, be done at the beginning of each sunitinib treatment cycle.

Sutent

The package insert for sunitinib contains a bold-faced warning about the risk of left ventricular dysfunction potentially associated with sunitinib. Those who present with cardiac events within 12 months prior to starting on sunitinib should be monitored for signs and symptoms of congestive heart failure (CHF) during treatment. Pfizer recommends the discontinuation of sunitinib in the presence of clinical manifestations of CHF. Other common adverse effects included mouth pain/ irritation, fatigue, asthenia, hemorrhaging, and altered taste.

The recommended dose of sunitinib for GIST and MRCC is one 50-mg oral dose once daily, on a schedule of four weeks on treatment followed by two weeks off, Hutson said. Pfizer advises a dose reduction to a minimum of 37.5 mg daily if sunitinib is to be given concomitantly with a strong cytochrome P4503A4 (CYP3A4) inhibitor, and a dose increase to a maximum of 87.5 mg daily if sunitinib is to be given concomitantly with a strong CYP3A4 inducer.