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Drug shows promise for the first time against metastatic melanoma of the eye
Date:6/19/2014

EK, a key enzyme in the MAPK pathway, can inhibit the growth of uveal melanoma cells in the laboratory. Dr. Schwartz's laboratory was the first to show this with selumetinib.

In 2013, Dr. Schwartz and his colleagues launched the first large-scale, Phase II, randomized trial of selumetinib. One hundred and one patients with metastatic uveal melanoma at 15 centers in the United States and Canada were randomized to receive either selumetinib or standard chemotherapy. Those in the chemotherapy group could receive selumetinib at any time if they showed signs of disease progression.

Median progression-free survival among patients receiving selumetinib was more than double that of patients receiving chemotherapy (15.9 weeks vs. 7 weeks). Forty-nine percent of patients treated with selumetinib exhibited tumor regression, compared with none in the chemotherapy group.

Median overall survival for patients on selumetinib was 11.8 months, compared with 9.1 months for those on chemotherapy, but the difference was not statistically significant. "We suspect that there may have been improvement in survival in the selumetinib group, but it was unclear, because patients who didn't respond to chemotherapy were allowed to cross over to selumetinib," said Dr. Schwartz. "That's something we hope to clarify in a follow-up study that is now under way."

The vast majority of patients taking selumetinib experienced side effects, including rash, swelling, and visual changes. Most of the side effects were considered manageable, although 37 percent of patients required at least one dose reduction and 6 percent discontinued therapy.

Dr. Schwartz thinks that treatment of uveal melanoma will ultimately involve rational drug design and a combination of drugs, similar to the approach used to combat HIV infection. "In preclinical studies, we've shown that when a MEK inhibitor was combined with an Akt inhibitor, which affects another cancer-related pathway, the r
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Contact: Karin Eskenazi
Ket2116@columbia.edu
Columbia University Medical Center
Source:Eurekalert  

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