In a nutshell
The authors investigated the effectiveness and patient response (tolerance) to vemurafenib (Zelboraf) treatment in advanced melanoma.
Some background
In advanced melanoma (stage III/ IV), cancer spreads from the skin to other parts of the body (metastasis). BRAF genes are often mutated (permanently changed) in advanced melanoma. These genes are involved in cellular signaling and important protein function, such as MAPK and MEK proteins. In BRAF mutated melanoma, these proteins remain permanently active. This results in the uncontrolled growth of cancer cells. BRAF inhibitors, such as vemurafenib, inhibits MEK and MAPK proteins in BRAF mutated cells. BRAF inhibitors have shown significant improvement in the treatment of melanoma. However, adverse events (side-effects) and resistance to vemurafenib treatment frequently occur, the reasons of which are currently unknown.
Further research is needed to determine the appropriate dosing of this drug.
Methods & findings
The aim of this study was to determine the effectiveness of vemurafenib in patients with advanced BRAF mutated melanoma.
105 blood samples from 23 patients were analyzed in this study. Blood samples were collected at each tumor response evaluation (used to assess the change in volume of tumors) or when side effects occurred. The initial vemurafenib dose was 960 mg for all patients. Later, the dose was reduced in 44% of patients due to side-effects. After a minimum of 14 days following drug or dose modification the median (mid-point) vemurafenib level in the blood was 54.0 µg/mL.
After 35 weeks of vemurafenib treatment, 12 patients experienced their first tumor progression (growth). The average vemurafenib level in the blood at the time of first progression was 38.8 µg/mL. This was compared to the average vemurafenib level when the cancer was stable or in partial or complete response (56.4 µg/mL). Partial response is a 50% decrease in tumor volume after treatment. Complete response is 100% disappearance of the tumor following treatment.
Low levels of vemurafenib in the blood and the presence of brain metastasis were independently associated with tumor growth.
The bottom line
The authors concluded that the level of vemurafenib in blood varied significantly in advanced melanoma patients. They further indicated that low levels of vemurafenib in the blood was associated with tumor growth.
The fine print
A larger patient population-based study is needed for results to be widely applied.
Published By :
Annals of oncology
Date :
Apr 21, 2015
