Researchers in Slovenia say they may have found a method for determining which mesothelioma patients are most likely to respond to chemotherapy and which may have toxic side effects. The answers may lie in subtle genetic differences called polymorphisms.
Chemotherapy with pemetrexed (Alimta) and a platinum-based drug like cisplatin is the primary first-line treatment for pleural mesothelioma. However, as the authors of the new report point out, there is great inconsistency in patient response to this treatment. The goal of their new study was to determine how polymorphisms impact the way mesothelioma patients respond to pemetrexed treatment.
Mesothelioma patients treated with pemetrexed as part of a randomized clinical trial were sorted according to two types of polymorphisms – those of the folate pathway and those related to six transporter genes. The folate pathway is the biochemical pathway for the nutrient folate and transporter genes regulate how compounds enter cells.
According to the report in Radiology and Oncology, patients with at least one polymorphism in the folate pathway had a significantly lower response rate and shorter progression-free survival than non-carriers. Polymorphisms in the transporter genes did not appear to influence mesothelioma survival but several were associated with toxicity. Mesothelioma patients with a certain type of transporter gene variation had a much lower chance of liver toxicity with pemetrexed treatment while those with another type of polymorphism had less gastrointestinal toxicity.
“These polymorphisms could serve as potential markers of pemetrexed treatment outcome in patients with malignant pleural mesothelioma,” writes lead investigator Katja Goricar, a pharmacogeneticist with the Institute of Biochemistry at the University of Ljubljana.
As with most types of cancer, early diagnosis and treatment is the key to improved outcomes with mesothelioma. If polymorphisms could be used to help predict patient response, patients could potentially save valuable treatment time by avoiding therapies that are unlikely to be effective .
Goricar, K, et al, “Polymorphisms in folate pathway and pemetrexed treatment outcome in patients with malignant pleural mesothelioma”, April 25, 2014, Radiology and Oncology, pp. 163-172.