New Chemotherapy Approaches for Mesothelioma
Posted on Sunday, August 05, 2012.

A pair of new studies may help doctors improve the effectiveness of chemotherapy treatment for mesothelioma.

The first of two new chemotherapy studies tested the value of adding bevacizumab to the drug combination of cisplatin and pemetrexed often used to treat mesothelioma. Bevacizumab (Avastin) inhibits angiogenesis, the growth of new blood vessels needed to feed cancer cells. It is currently used to treat a number of different cancers, including colorectal, lung, kidney and ovarian cancer. In the U.S., it has also been used to treat the brain cancer glioblastoma.  Results have been mixed.

In a multicenter study led by researchers at the University of Texas Southwestern Medical Center, bevacizumab was added to the cisplatin/pemetrexed combination for 52 previously untreated mesothelioma patients. The patients chosen for the study could not be candidates for surgery.

Although more than half of the study participants (56%) experienced progression-free survival at 6 months, the figure did not reach the 33% improvement rate researchers were looking for. In addition, a number of patients experienced serious toxicities including neutropenia (reduction in white blood cells), hypertension and venous thromboembolism (blood clot), suggesting that bevacizumab is not an efficacious addition to the standard mesothelioma chemotherapy protocol.

Another chemotherapy study out of Egypt may be more promising. In that small study, a team of doctors tested whether adding the drug methotrexate directly to the pleural space around the lungs of mesothelioma patients could result in a higher concentration of the drug, without the toxicities associated with systemic methotrexate use. Methotrexate is an antimetabolite used to treat psoriasis, rheumatoid arthritis, lung, breast, uterine and some blood cancers.  It is one of the oldest chemotherapy agents still in use.

In the study, five mesothelioma patients were treated with 3 cycles of methotrexate, infused directly into the pleural cavity. With each treatment, the amount of drug given was increased. Levels of methotrexate in the pleural fluid and the blood serum were tested daily.

By infusing the drug directly into the pleural cavity, researchers found no grade II toxicities, even at high doses. Just as importantly, a much higher concentration of the drug stayed in the pleural space, closer to the location of the target mesothelioma cells. They wrote, “This approach allows attaining methotrexate pleural levels that are 95 to 3,000 times higher than systemic serum levels, with minimal toxicity.” 

The study’s authors conclude that their results warrant a larger, formal phase II study on the pleural infusion of methotrexate.


Dowell, JE, “A multicenter phase II study of displatin, pemetrexed, and bevacizumab in patients with advanced malignant mesothelioma”, July 4, 2012, Lung Cancer Epub ahead of print.
Ellithy, MM, “infusion of Escalated Doses of Methotrexate in Malignant Pleural Mesothelioma”, July 9, 2012, American Journal of Clinical Oncology, Epub ahead of print.


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