Vorinostat Treatment Study for Mesothelioma Enters Phase III

Under the brand name Zolinza®, vorinostat has been used in the treatment of skin cancer since October of 2006. On 7 September 2007, the National Institute of Health (NIH) announced that an ongoing study of the drug’s effectiveness in the treatment of malignant pleural mesothelioma is entering a Phase III clinical trial.
What Is Vorinostat? The technical name of vorinostat is suberoylanide hydroxamic acid. Approved by the FDA in the fall of 2006, the drug has been used in cases of cutaneous T-cell lymphoma, a type of cancer that starts in the lymphatic system and appears on the skin. Vorinostat is what the medical profession classifies as a “histone deacetylase inhibitor.” These drugs slow the action of enzymes, which are proteins that act as a catalyst for biological processes at the cellular level, including cell growth. Histone deacetylase is one such enzyme that assists in the organization of DNA. Vorinostat alters this process at the genetic level in a way that causes tumor cells to die off, inhibiting the spread of the cancer.

A June 2007 study at the Mayo Clinic indicated that vorinostat may be effective in the treatment of glioblastoma multiforme, a particularly deadly form of brain cancer. A New Mesothelioma Treatment? Mesothelioma, a cancer of the pleural lining of the lung, spreads in a sheet-like manner rather than as lumps, making it difficult to diagnose. As a result, most cases are not discovered until the disease has reached its later stages, at which point treatments can only relieve symptoms. Using a combination of invasive surgery, radiation treatments and chemotherapy, patients diagnosed with mesothelioma survive for 12 months on the average. Vorinostat has several advantages over traditional treatments; it can be taken orally, and is readily absorbed and utilized by the body. Among 200 test subjects in Phase I and II trials, the most common side-effects were fatigue, nausea, and hyperglycemia.

About half of the subjects experienced gastro-intestinal irritation, and a small number suffered from a decrease in white blood cells and bleeding gums and/or nose. These side effects disappeared when the drug was discontinued. The response rate among Phase I and II subjects with mesothelioma was 2 in 13. The Phase III trial currently underway will include 660 patients who have previously been treated with the chemotherapy pemetrexed, a common treatment for mesothelioma and certain “non-small cell” lung cancers.