Experimental Drugs Battle Melanoma Nicely

Metastatic melanoma was treated with an experimental drug combination in clinical trials

(RxWiki News) Sometimes drug combinations work better than one drug alone. First, though, studies need to determine whether the combination is safe, what the best dosage range is and evaluate overall effectiveness.

A recent clinical trial tested two unapproved melanoma drugs in a combination therapy. Many side-effects were found, but improved rates of stalling the cancer were also seen.

"Talk to your doctor about your best treatment options."

Keith T. Flaherty, MD, associate professor at Harvard Medical School and director of developmental therapeutics in the Cancer Center at Massachusetts General Hospital, and Jeffrey Weber, MD, PhD, director of the Melanoma Research Center at Moffitt Cancer Center in Florida, teamed up for a multi-phase clinical trial.

For the study, 443 melanoma patients from 16 cancer centers participated in a clinical trial to test a dual-drug combination from 2010-2011.

Melanoma can occur as a result of a gene mutation. However, not all melanomas are the result of the same gene mutations. Approximately half of melanomas are the result of changes in the BRAF gene.

Each of the patients had a history of metastatic melanoma with either BRAF V600E or BRAF V600K mutations.

Dabrafenib and trametinib are drugs designed to treat melanoma. They work by targeting different molecules.

Neither drug, individually nor in combination, have been approved by the U.S. Food and Drug Administration (FDA). The drugs have only being tested in clinical-trial settings.

Half of the patients treated with either drug, in past trials, still saw their melanoma worsen within 6-7 months.

Scientists focused on drug interactions side-effects, safety and varied dosages with the drug combination.

Dosage was at 150 mg of dabrafenib twice daily and 1 mg of trametinib once daily for one group, and went up to 150 mg of dabrafenib twice daily and 2 mg of trametinib once daily for another group.

Researchers observed:

• Melanoma tumors beneath the skin reduced to 3 percent with the combination of dabrafenib and trametinib, compared to 20 percent with dabrafenib alone

• Skin rashes present in 20 percent of the 150/1 group, 27 percent of the 150/2 group and 36 percent for the dabrafenib-only group.

• Fever, chills, fatigue, vomiting, diarrhea and headache were the most common side-effects experienced.

• A total of 58 percent of study participants had to have dosages reduced due to side-effects.

• The average patient remained on combination therapy for about 11 months. Nearly half, 41 percent, of the maximum dosage group saw no tumor progression after 12 months.

• At the maximum dosage, no tumor progression lasted for 9.4 months compared to 5.8 months for the dabrafenib-only group.

• At the 12 month mark, 79 percent of patients on 150/2 dosage were alive.

Authors concluded, “We believe that the combination of dabrafenib and trametinib warrants further evaluation as a potential treatment for metastatic melanoma with BRAF V600 mutations and other cancers with these mutations.”

This study was published in September in the New England Journal of Medicine.

Funding for the study was provided by GlaxoSmithKline.

Study authors reported no conflicts of interest.

Review Date: 
October 2, 2012