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The Food and Drug Administration has approved the use of pazopanib (Votrient, made by GlaxoSmithKline) for the treatment of patients with advanced soft tissue sarcoma who have received prior chemotherapy. The U.S. label notes, however, that the efficacy of the drug, a multi-targeted receptor tyrosine kinase inhibitor that interferes with angiogenesis, has not been demonstrated for patients with adipocytic soft tissue sarcomas or gastrointestinal stromal tumors (GIST).

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The approval was based on the results of the pivotal, randomized, double-blind, placebo-controlled, multi-center Phase III "PALETTE" (PAzopanib ExpLorEd in sofT Tissue sarcoma) GlaxoSmithKline-EORTC study, which was led by George Demetri, MD, Director of the Center for Sarcoma and Bone Oncology at Dana-Farber Cancer Institute.


The approval is the first for such sarcomas overall in decades-"the last time was when Nixon was president," he noted in a telephone interview.


"This is a wonderful thing for these patients, who have looked longingly at the success of Gleevec for patients with GIST," and now patients with these other sarcomas can start to have the benefits of molecularly targeted therapy.


Richard Pazdur, MD, the FDA's Director of the Office of Hematology and Oncology Products in the Center for Drug Evaluation and Research, noted in a statement that drug development for soft tissue sarcomas, a diverse group of tumors, has been especially challenging because of the relative rarity of the cancers, and therefore the limited number of patients, as well as the fact that there are multiple subtypes of sarcomas.


The safety and effectiveness of Votrient was evaluated in a single clinical study in 369 patients with advanced soft tissue sarcoma who had received prior chemotherapy. Patients were randomly selected to receive Votrient or a placebo. The disease did not progress for a median of 4.6 months for patients receiving Votrient, compared with 1.6 months for those receiving the placebo.


The most common side effects in patients receiving Votrient were fatigue, diarrhea, nausea, weight loss, high blood pressure, decreased appetite, vomiting, tumor and muscle pain, hair color changes, headache, a distorted sense of taste, shortness of breath, and skin discoloration.


Demetri said the mechanism of action is still unclear, but it definitely does work to stabilize disease.


The drug carries a boxed warning alerting patients and health care professionals to the potential risk of fatal hepatotoxicity, and noting that patients should be monitored for liver function and treatment discontinued if liver function declines.


Votrient, which was previously approved in 2009 for the treatment of advanced kidney cancer, had also been granted Orphan Drug Status for the sarcoma indication, which is given to a drug intended to treat a disease affecting fewer than 200,000 patients in the United States.