Pharmacology Update

Sunitinib Maleate Capsules (Sutent®)

By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationships to this field of study.

The FDA has approved a new drug for the treatment of gastrointestinal stromal tumor and metastatic renal cell cancer. Sunitinib is an orally active, highly selective, multi-targeted tyrosine kinase inhibitor. The drug was given a priority review and was approved in less than 6 months. Sunitinib is marketed by Pfizer as Sutent®.


Sunitinib is indicated for the treatment of gastrointestinal stromal tumor (GIST) after progression on or intolerance to imatinib. It is also indicated for the treatment of advanced renal cell carcinoma (RCC).1


The recommended dose for GIST and advanced RCC is 50 mg capsule taken once daily for 4 weeks on and 2 weeks off. Dose reduction to a minimum of 37.5 mg should be considered if sunitinib is co-administered with a strong CYP3A4 inhibitor (eg, ketoconazole, itraconazole, protease inhibitors). A dose increase should be considered to a maximum of 87.5 mg if sunitinib is co-administered with a CYP3A4 inducer (eg, rifampin). Sunitinib may be taken without regard to meals.

Sunitinib is supplied as 12.5 mg, 25 mg, and 50 mg capsules.

Potential Advantages

Sunitinib has been shown to prolong time to tumor progression in patients with GIST resistant to or intolerant to imatinib. In patients with RCC sunitinib has been shown to reduce tumor size.

Potential Disadvantages

Serious adverse events have been reported with sunitinib. These include left ventricular dysfunction, hemorrhagic events, hypertension, myelosuppression, and reduced adrenal function. Other adverse events include diarrhea, nausea, stomatitis, dyspepsia, vomiting, skin discoloration, fatigue, mouth pain/irritation, and taste disturbance.1


Sunitinib is a multitargeted tyrosine kinase inhibitor. Targets include vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2), platelet-derived growth factor receptors, and stem cell factor receptors.1,2 It has demonstrated antitumor and antiangiogenic activity. In a randomized, double-blind, placebo-controlled trial in patients with GIST whose disease progressed on imatinib or who were intolerant of imatinib (n = 312), sunitinib (50 mg daily; 4 weeks on and 2 weeks off) was found to significantly improve time-to-tumor progression and progression-free survival compared to placebo.1 The median time to tumor progression for sunitinib vs. placebo respectively was 27.3 (95% CI, 16.0%-32.1%) weeks vs 6.4 (95% CI, 4.4%-10.0%) weeks and median progression-free survival was 24.7 (95% CI, 11.1%-28.3%) and 6.6 (95% CI, 4.4%-9.9%) weeks respectively. The partial response rate was 6.85 (95% CI, 3.7%-11.1%). In 2 single-arm studies in patients with metastatic RCC (n = 106 and 63) who had progressed on cytokine-based therapy, sunitinib showed response rates of 25.5% and 36.5%.1 Objective response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST).3 Median duration of response was 54 (95% CI, 24.7-49.6) weeks in one study. The second study was still in progress when data were collected.1 Common adverse events include fatigue, myelosuppression, skin discoloration, taste disturbance, bleeding, and gastrointestinal symptoms. Patients should be monitored for left ventricular dysfunction, hypertension, CBC and platelet counts, thyroid function, and pancreatic function. Dosage adjustment is required if sunitinib is co-administered with a strong CYP3A4 inhibitors and inducers.

Clinical Implications

Imatinib is a first-line treatment for unresectable and/or metastatic GIST.4,5 Sunitinib provides a treatment option in patients who have failed or are intolerant of imatinib. For metastatic RCC, adjunct therapy with conventional chemotherapy, interferon alfa, or interleukin-2 has not been effective.3,6 Sunitinib provides an agent with a measurable response rate. It joins sorafenib as recent approvals for advanced RCC. There are approximately 32,000 new cases of advanced renal cancer and 5,000 cases of GIST annually.7


1. Sutent Product Information. Pfizer Laboratories. January 2006.

2. Faivre S, et al. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol. 2006;24:25-35.

3. Motzer RJ et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006;24:16-24.

4. van der Zwan SM, DeMatteo RP. Gastrointestinal stromal tumor: 5 years later. Cancer. 2005;104: 1781-1788.

5. Sanborn RE, Blanke CD. Gastrointestinal stromal tumors and the evolution of targeted therapy. Clin Adv Hematol Oncol. 2005;3:647-657.

6. Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med. 2005:353:2477-2490.

7. FDA News: Accessed 2/18/06.