Preliminary study shows promise for treatment of renal cell cancer

A new study suggests that sunitinib is a promising agent for treatment of metastatic renal cell cancer, currently a disease without highly effective treatment options, according to an article in the June 7 issue of JAMA.

There is an urgent need for more active agents for the treatment of metastatic (spread of cancer from point of origin to another part of the body) renal cell carcinoma (RCC). The 5-year survival rate for metastatic RCC is estimated to be less than 10 percent, according to background information in the article. RCC is highly resistant to chemotherapy, and only a limited subset of patients (20 percent or less) benefit from cytokine (proteins from the immune system) therapy (high-dose interleukin-2 [IL-2] and/or interferon-alfa). Overall median survival following progression after cytokine therapy is approximately 10 to 13 months, and no effective treatment is available for patients whose disease progresses after an initial response, or who do not respond to cytokine therapy.

A better understanding of the genetic abnormalities associated with clear-cell RCC has helped identify new targets for therapy, and subsequently the development of a new therapy, the oral medication sunitinib, which had positive results in an initial study.

Robert J. Motzer, M.D., of Memorial Sloan-Kettering Cancer Center, New York, and colleagues conducted a multicenter phase 2 trial to confirm the antitumor efficacy of sunitinib in 106 patients with metastatic clear-cell RCC whose disease was refractory (unresponsive) to 1 prior cytokine therapy. Patients were enrolled between February and November 2004, with follow-up continuing until disease progression, unacceptable toxicity, or withdrawal of consent. Patients received repeated 6-week cycles of sunitinib, 50 mg per day given orally for 4 consecutive weeks followed by 2 weeks off per treatment cycle.

"The results of this trial confirm that sunitinib given once daily according to a 4 weeks on/2 weeks off schedule has substantial antitumor effects against metastatic clear-cell RCC. Of the 105 evaluable patients, 36 patients achieved partial response (34 percent), and a median progression-free survival of 8.3 months as evaluated by the independent third-party core imaging laboratory (resulting in a value considerably longer than expected in this clinical setting)," the authors write.

The most common adverse events experienced by patients were fatigue 30 (28 percent) and diarrhea 21 (20 percent).

"The results of this trial demonstrate the efficacy of sunitinib as a single agent in second-line therapy for patients with cytokine-refractory metastatic clear-cell RCC. The initial observation of antitumor activity for sunitinib has been confirmed in a larger trial. Sunitinib as a first-line therapy for metastatic clear-cell RCC is currently being investigated vs. interferon-alfa in a randomized phase 3 study," the researchers conclude.

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(JAMA. 2006;295:2516-2524. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: Research support for this trial was provided by Pfizer Inc. For the financial disclosures of the authors, please see the JAMA article.

Editorial: A New Strategy in the War on Renal Cell Cancer

In an accompanying editorial, Boris Pasche, M.D., Ph.D., of the Northwestern University Feinberg School of Medicine, Chicago, comments on the findings of Motzer et al.

"This trial represents another example of rational cancer therapy based on cancer-specific molecular alterations. Objective responses were observed in 34 percent of patients. Given the dismal track record of chemotherapy in the treatment of RCC, this is nothing short of remarkable. These results extend and confirm the results of a previous phase 2 study conducted on a smaller number of patients and establish sunitinib as a bona fide therapeutic agent in this disease."

"Postapproval trials will be needed to demonstrate clinical benefit, such as increased survival or improvement in disease-related symptoms. The short median progression-free survival (8.3 months) highlights the fact that sunitinib is far from a magic bullet. Nonetheless, it represents a new class of drug with a promising future for the treatment of this deadly disease. In the war on cancer, it is a small victory against one of the most ferocious enemies."

(JAMA. 2006;295:2537-2538. Available pre-embargo to the media at www.jamamedia.org)


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