Is Dactinomycin A Antifolate Drug Mesothelioma, Pdf Hodgkin Lymphoma Derived Cells Show High Sensitivity To Dactinomycin And Paclitaxel

Mesothelioma patients have few viable treatment options.

Focal pleural thickening ct. Pemetrexed is the first agent approved for the treatment of mpm. In august 2004 pemetrexed was approved as a second line single agent. Metabolic characterization of antifolate responsiveness and non responsiveness in malignant pleural mesothelioma cells.

Radiation therapy is limited by its. For most mesothelioma patients chemotherapy with alimta is the first treatment they receive. Antifolate drugs produce an intracellular state of folic acid deficiency in order to inhibit folate dependant enzymes along the folate metabolic pathway.

We report the presence of a novel concentrative high affinity transport activity in three human mesothelioma cell lines characterized in detail in the nci h28 line with a pemetrexed influx k t of 30 nm and v max of 10 nmolg. In a 60 patient trial high dose methotrexate yielded a 37 response rate and a median survival of 11 months the cancer and leukemia group b calgb reported a response rate of 25 and significant toxicity in a phase ii trial of edatrexate. Other common nsaid drugs like aspirin phenylbutazone salicylate probenecid and trimethoprim should also be monitored carefully during the use of antifolate drugs.

Both response and toxicity were decreased by the addition of leucovorin. New antifolate drugs pemetrexed or raltitrexed in combination with platinum are associated with longer median survival than platinum alone an increase which averages about three months. Hela sublines expressing exclusively pcft r1 11 pcft4 or rfc r1 11.

We examined whether the novel 6 substituted pyrrolo23 dpyrimidine thienoyl antifolate compound 2 might be an effective treatment for malignant pleural mesothelioma mpm reflecting its selective membrane transport by the proton coupled folate transport pcft over the reduced folate carrier rfc. Patients under the medication of antifolates should avoid drinking alcoholic drinks completely because it increases the risk of developing hepatic fibrosis and cirrhosis. There has not been a new drug for mesothelioma since alimta pemetrexed received fda approval in 2004.

Pemetrexed is a novel antifolate effective in the treatment of mesothelioma. Mesothelioma is a malignant tumour of pleura and other serosal tissues. Alimta is an antifolate that is also approved for non small cell lung cancer.

Dna synthesis and cell division processes involved in malignant tumor growth are hindered by folic acid deficiency. In order to select the most suitable patients for effective therapy with drugs targeting specific metabolic pathways there is a need for better predictive metabolic biomarkers. Studies were undertaken to characterize the transport of this antifolate in this tumor.