The clinical trial shows that selumetinib drug can delay the progression of metastatic uveal melanoma

The clinical trial shows that selumetinib drug can delay the progression of metastatic uveal melanoma -

For the first time a therapy has been found that can delay the progression of melanoma metastatic uveal, a rare and deadly form of melanoma of the eye.
the results of a series of multicenter clinical trials of a new drug called selumetinib increases progression-free survival, duration of time during and after treatment that a patient with metastases living with the disease without it progresses. The results were published today in the online edition of JAMA on Journal of the American Medical Association .
"Although the drug effects were modest, now we know we can influence the course of the disease, and we expect to build on this success with other medications, including some already developing, "said lead author Gary K. Schwartz, MD, professor of medicine and chief of hematology / oncology at NewYork-Presbyterian / Columbia University medical Center and associate director of the Herbert Irving Comprehensive Cancer Center. ( at trial, Dr. Schwartz was head of service melanoma and Kaposi at Memorial Sloan Kettering cancer Center in New York.)
the uveal melanoma is a cancer of the iris, the ciliary body, or choroid -the eye structures collectively known as the uvea. uveal melanoma (which is biologically distinct from cutaneous melanoma) generated by the melanocytes of the uvea, the pigment cells that give the eye its color . once the disease has spread most distant metastases-existing liver treatments are largely ineffective. Approximately 1500 cases of uveal melanoma occur in the US each year, usually in the elderly. The median survival rate for patients with metastatic uveal melanoma is 12 months.
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several years, researchers found that 80 percent of patients with uveal melanoma had mutations in GNAQ or GNA11, genes that activate signals in the mitogen-activated protein kinase (MAPK) . Dr. Schwartz and others subsequently demonstrated that inhibition of MEK, a key enzyme in the MAPK pathway, can inhibit the growth of uveal melanoma cells in the laboratory. The laboratory of Dr. Schwartz was the first to show that 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 in 15 centers in the United States and Canada were randomized to receive either standard chemotherapy or selumetinib. Those of chemotherapy group could receive selumetinib at any time if they showed signs of disease progression.
The median progression-free survival in patients receiving selumetinib was more than double that of patients receiving chemotherapy (15.9 weeks against 7 weeks). Forty-nine percent of patients treated with selumetinib showed tumor regression, compared with none in the group of chemotherapy.
The median overall survival for patients on selumetinib was 11.8 months against 9.1 months for those on chemotherapy, but the difference was not statistically significant. "We suspect it may have been an improvement in survival in the selumetinib group, but it was clear, because patients who did not respond to chemotherapy were allowed to cross to selumetinib," said Dr. Schwartz . "This is something we hope to clarify in a follow-up study is underway."
The vast majority of patients taking selumetinib experienced side effects including rash, swelling and visual changes . most side effects were considered manageable, although 37 percent of patients required at least one dose reduction and 6 percent discontinued treatment.
Dr. Schwartz thinks the treatment of uveal melanoma will ultimately involve the rational design of drugs and a combination of drugs, similar to the approach used to fight against HIV. "in preclinical studies, we have shown that, when an inhibitor MEK was combined with an inhibitor of Akt, which affects a different path associated with cancer, the results were better than when using only one of MEK, "he said.
"overall," Dr. Schwartz added, "the study highlights the importance of rational drug design, in which drugs are designed to interact with specific molecular pathways involved in disease special. This is a huge improvement over chemotherapy, which is essentially a comprehensive approach to cancer that does not directly address the underlying biology. "