Mixed Results for Mesothelioma From Targeted Therapies

A review of recent clinical trials on various targeted therapies for malignant mesothelioma indicates that, while some are helpful, none are likely to become standard treatments yet.

In an article in the international journal Cancer Chemotherapy and Pharmacology, a pair of Danish researchers reported their analysis of 32 clinical trials on 17 different targeted agents for mesothelioma. A targeted agent is a medication that takes aim at a specific cellular function within mesothelioma tumor cells. Some inhibit proteins needed for growth or replication. Others may attack the formation of blood vessels or other structures that feed the cancer cells.

The extensive look at clinical trials of these targeted agents found that, overall, those that were used as a first-line treatment for mesothelioma induced responses ranging from 0 to 14%. Those that were used as a second-line treatment, after another therapy had already been tried, induced a 0 to 16% response. One of the more effective targeted agents appears to be sunitinib (brand name Sutent), a tyrosine kinase inhibitor that triggered some tumor shrinkage in 10% of mesothelioma patients, but resulted in ‘stable disease’ for 66% of them when used as a second-line treatment.

Another potentially effective targeted agent for some mesothelioma patients is bevacizumab (brand name Avastin). Bevacizumab is a monoclonal antibody and the first FDA-approved therapy designed to inhibit angiogenesis, the process by which new blood vessels form to support cancer cells. Primarily used for the treatment of metastatic colorectal cancer, recurrent metastatic non-squamous non-small cell lung cancer, and metastatic renal cell carcinoma, it is being tested as an addition to chemotherapy for mesothelioma patients.

As reported by the Danish researchers, some of the results of Avastin trials have been positive. When added to pemetrexed and cisplatin chemotherapy drugs, bevacizumab ‘significantly improved disease control in 73.5% of mesothelioma patients, compared to 43.2% who had chemotherapy alone. Bevacizumab did not appear to offer the same advantages when used along with another chemotherapy combination – gemcitabine and cisplatin. Unfortunately, other studies suggest that the drug may increase the risk of kidney damage.

The results of these mesothelioma trials prompted the authors of the meta-analysis to cautiously conclude, “Disease stabilization is reported in some patients with several targeted treatments and might be beneficial in subgroups of patients or in combination with classic chemotherapy.” They add, however, that none of the current targeted treatments available are effective enough to be recommended as standard treatment for malignant mesothelioma.

Source:

Jakobsen, JN and Sorensen, JB, “Review of clinical trials of targeted treatments in malignant mesothelioma”, May 7, 2011, Cancer Chemotherapy and Pharmacology, Epub ahead of print. Phend, Crystal, “Kidney damage Affirmed with Biologic-Chemo Combo”, June 10, 2011, MedPage Today.