not sure if this is any help or not. from poche centre sydney. biggest melanoma clinic in australia

Australian researchers help show two-drug melanoma combination helps slow cancer in study

3rd October 2012

Australian researchers at Melanoma Institute Australia and Westmead Hospital in Sydney have published the results of a study that shows a combination of two experimental melanoma drugs helped slow the cancer’s progress longer than a single-drug treatment.

Patients taking the new melanoma drugs dabrafenib and trametinib together delayed tumors from progressing for 9.4 months, compared with 5.8 months for patients taking dabrafenib alone, according to the study of 162 patients. The trial was part of the second of three phases of studies by researchers in Australia, the US and Europe.

Dabrafenib works by blocking BRAF, a mutant gene that spurs cancer-cell growth in about half of melanoma patients, while at the same time, trametinib thwarts a related protein called MEK, which helps tumours resist an attack on BRAF.

The study, funded by the pharmaceutical company GSK, was presented at the European Society for Medical Oncology meeting in Vienna over the weekend by Dr Georgina Long from Melanoma Institute Australia, Westmead Hospital and The University of Sydney, and simultaneously published in the New England Journal of Medicine.

The phase I and II trials focused on combining two drugs to delay the resistance to BRAF inhibition. The study tested two doses of trametinib. The combination of drugs prolonged progression-free survival over single-drug therapy from 5.8 months to 9.4 months, which represented a 60% improvement. Among patients who received both drugs at the higher dose, 41 percent had not progressed 12 months after treatment began, compared with 9 percent in the single-drug arm of the study.

Patients taking the two medicines together had lower incidence side effects including rash and skin lesions, often associated with single agent dabrafenib.

Adding the MEK drug may reduce a side effect of BRAF drugs, the development of non-melanoma skin cancer, while possibly boosting efficacy, according to Dr Georgina Long, a study leader and oncologist with Melanoma Institute Australia and Westmead Hospital in Sydney.

Dr Long said, “Understanding melanoma and its mutations helps highlight more deadly weaknesses of the cancer, which we can exploit using new drugs and drug combinations.”

“We know that resistance emerges within 5-6 months of treating patients with single-agent selective BRAF inhibitor. We also know that most of the resistance mechanisms identified so far result in re-activation of the pathway that the BRAF inhibitor initially blocked (MAP kinase pathway). This was the basis of the rationale to trial the addition of a MEK inhibitor. It blocks the same pathway, but lower down, and we hoped that by combining both drugs we would see a significant delay in the emergence resistance that would impact patients lives.”

“The combination therapy of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib prolongs the progression-free survival in patients with V600 BRAF mutation-positive metastatic melanoma compared with dabrafenib monotherapy. Importantly, the combination also decreases the rate of the cutaneous toxicities compared with dabrafenib monotherapy, particularly the oncogenic cutaneous toxicity of squamous cell carcinoma,” Dr Long said.

Download press release

this is the website

http://www.melanoma.org.au/