PLX4032
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Early-stage melanoma that is confined to a spot on the skin can be surgically removed and
in most cases stopped. But patients’ prospects take a deadly turn if the cancer
metastasizes, or spreads, to other parts of the skin or to internal organs. Chemotherapy
drugs benefit fewer than 20 percent of such patients.

The drug, PLX4032 (also known as RG7203), just completed a phase 1 clinical trial in which
81 percent of participants with a particular gene mutation had a partial response, meaning
at least some shrinkage of the tumor. The current standard treatments for metastatic
melanoma -- chemotherapy and interleukin-2 (IL2) -- only have response rates in about 15
percent of these patients and so this is a good news.

Currently, PLX4032 is the first potent inhibitor of BRAF that has made it to the clinical trial
stage. In this phase I trial, 10 of the 16 patients with melanoma tumors carrying the V600E
mutation in the serine–threonine protein kinase B-RAF (BRAF) gene had a partial response
when treated with at least 240 mg of PLX4032A.

The study released in August 2010 documented the results of two phases of tests involving
PLX4032, the first to determine the optimum dose and the second to examine the drug's
effectiveness.

During the first phase, 55 patients received gradually escalating doses that allowed
scientists to determine that a twice-daily dose of 960 milligrams would be optimal.

The second stage involved 32 patients with BRAF-mutated melanomas, 26 of whom saw
their tumors shrink more than 30 percent, including two whose tumors disappeared
altogether.

The drug proved capable of shrinking metastatic tumors in the liver, small bowel, bone and
thyroid and produced minor side-effects.

In the entire treated cohort, the estimated median progression-free survival extended more
than seven months with a substantial proportion still on study. Recently, scientists reported
that another experimental drug, ipilimumab, prolonged median survival in patients with
metastatic melanoma from 6.4 months to 10 months.

So the novel agent isn't a cure for melanoma.

SOURCES
[1] Crystal Phend, Targeted Therapy Shows Early Promise in Melanoma, medpagetoday.
com, August 2010 [2] Amanda Gardner In Early Trial, Targeted Therapy Fights Advanced
Melanoma HealthDay News Aug. 25 2010 [3] New drug shrinks many advanced
melanomas: study AFP Aug. 25 2010[4] Aug. 26 New England Journal of Medicine [5] New
drug fights metastatic melanoma sciencenews.org Aug 2010