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Possible Second-Line Mesothelioma Treatment Fails

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There has been some disappointing news for mesothelioma patients who fail to respond to first-line chemotherapy treatment. A major Phase III clinical study of a potentially promising second-line drug treatment showed no effect on survival.

Mesothelioma researchers had high hopes for vorinostat (brand name Zolinza), a histone deacetylase inhibitor that alters gene expression and protein activity inside cells. Earlier studies found that a small number of mesothelioma patients treated with the drug had stable disease that lasted for 13 months. But in the current study – one of the largest mesothelioma trials of its kind – vorinostat offered no statistically significant survival advantage.

The study involved 660 mesothelioma patients from 92 sites. The median age was 65. Patients were given 300 mg of vorinostat twice daily, three days a week, for three weeks. Researchers were specifically looking at overall survival and how well the medicine was tolerated.

Although the adverse effects were slightly higher in patients taking the drug in comparison to those taking placebo, the tolerability results were comparable. Mesothelioma patients on vorinostat survived a median of 30.7 weeks compared to 27.1 weeks in the placebo group. There were no differences in terms of response rate, forced vital capacity or dyspnea (shortness of breath) score.

Lead researcher, Lee Krug, MD, of Memorial Sloan-Kettering Cancer Center in New York reported the results of the study at a presidential session of the European Multidisciplinary Cancer Congress in Stockholm, Sweden. The study was supported by the drug’s manufacturer, Merck.

The vorinostat study is a blow particularly because there is no standard second-line chemotherapy for mesothelioma patients. Mesothelioma patients who fail to respond to the standard pemetrexed/cisplatin chemotherapy combination often have difficulty determining clinical “next steps.”

An estimated 2.500 Americans are diagnosed with mesothelioma each year. Because the disease typically carries such a poor prognosis, global efforts are underway to find more effective treatments.


Fiore, Kristina, “ECCO-ESMO: Drug for Mesothelioma Fails Trial”, September 28, 2011, MedPage Today website. Krug LM, et al “Vorinostat in patients with advanced malignant pleural mesothelioma who have failed prior pemetrexed and either cisplatin or carboplatin therapy: A phase III, randomized, double-blind, placebo-controlled trial” ECCO-ESMO 2011; Abstract 3BA.

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