In a nutshell
The authors aimed to determine the effects of GC1008 (Fresolimumab) as a treatment option in advanced malignant melanoma.
Some background
Transforming growth factor beta (TGFβ) is a protein in the body that helps to maintain cell growth and the immune system. In advanced cancer TGFβ can lose this function and can instead promote tumor growth. Elevated levels of TGFβ can also indicate a more advanced cancer stage and poor survival and as a result is an attractive drug target. GC1008 is a drug that stops TGFβ from working, and is currently being investigated as a treatment in cancer.
Methods & findings
The aim of this study is to determine the safety and anti-tumor activity of GC1008 in patients.
29 patients were used in this study with an average age of 59 years. 28 patients had malignant melanoma and 1 patient had renal cell carcinoma (cancer of the kidney). 13 patients experienced at least one significant adverse event to GC1008, where two were drug-related and resulted in squamous cell carcinoma (cancer cell growth in upper skin layers) and shingles. Skin toxicity was the most common drug-related adverse event and occurred in 5 patients when receiving doses of 1mg/kg, 3mg/kg or 15mg/kg, with the majority occurring when higher doses of GC1008 were administered. All skin reactions cleared within weeks/months of completion of GC1008 treatment. 15mg/kg was identified as the maximal safe dose.
From 29 patients, 1 malignant melanoma patient achieved a partial response (some disappearance in signs and symptoms of cancer) when given an initial dose of 1mg/kg followed by an extended treatment of 4 doses at 3mg/kg. 6 patients experienced stable disease (no growth or reduction in tumor size) when given an initial dose of either 0.1, 0.3, 1.0, 3.0 or 15.0 mg/kg followed by an extended treatment dose of either 4 x 1mg/kg or 4 x 3mg/kg. Combined these 7 patients had an average time to disease progression of 24 weeks. The average progression free survival was 11.1 weeks for all 29 patients.
The bottom line
GC1008 demonstrates an acceptable safety profile in patients.
The fine print
The small patient numbers used in this study means that results can not be applied for larger groups of patients.
Published By :
PLOS ONE
Date :
Mar 11, 2014
