Gleevec (Imatinib Mesylate)

Gleevec is a chemotherapy drug developed in the 1990’s. It was originally designed to fight chronic myeloid leukemia (CML) and some rare forms of stomach cancer. CML is a condition in which there are too many white blood cells made in the bone marrow. Gleevec is manufactured by Novartis and is also known by its generic name Imatinib mesylate. It received FDA approval in 2001, specifically as a first line treatment for CML. It is also used to treat gastrointestinal stromal tumors (GIST) and other malignancies.

Gleevec was a new kind of chemotherapy drug when it was first developed. It attacks cancer cells in a different manner than the chemotherapy drugs that were available up until that time. Researchers had discovered a protein that was essential to the growth of cancer cells. They searched for a drug that would inhibit the growth of this protein and ultimately developed Gleevec.

Most chemotherapy drugs kill both cancer cells and normal cells because they do not act in a targeted way. But Gleevec, and other drugs of this class, target certain enzymes that are particular to that cancer cell and essential to the cancer’s development. Since Gleevec targets the specific cancer-causing cells, it causes less damage to non-cancerous cells. Because of the unique way in which Gleevec fights cancer, researchers have undertaken many other clinical trials to determine Gleevec’s effect on other cancers, including mesothelioma.

Initial Clinical Trials

The first clinical trials involving Gleevec were held in 1998 and were focused on its efficacy in treating leukemia, specifically CML. Like other Phase I clinical trials, the purpose was to determine whether Gleevec was safe for use in humans. Phase II trials came shortly thereafter as researchers determined that potential benefits were derived when higher doses of Gleevec were administered. In fact, the results were dramatic.

This drug was effective in leukemia patients when other chemotherapy drugs were no longer working. The results showed that Gleevec was very effective in treating CML. According to the National Cancer Institute, such dramatic results are rarely seen in early clinical studies of this nature. A larger follow-up study was conducted over the next two years and the favorable results were reported in the New England Journal of Medicine in April 2001.

Clinical Trials Related to Mesothelioma

Because of the dramatic results in the treatment of CML, researchers began to conduct clinical studies to see how effective Gleevec was in fighting other cancers. One of the clinical trials tested the effect that Gleevec alone had on mesothelioma patients. In a 2005 Phase II clinical study, the results showed that Gleevec alone produced no positive responses in patients with mesothelioma. (Reported in Lung Cancer, Volume 50, Issue 1, October 2005).

However, many chemotherapy drugs when used in combination with other chemotherapy drugs obtain much better results. A number of scientists, including Dr. Giovanni Gaudino, a visiting researcher at the Cancer Research Center of Hawaii, are combining Gleevec (Glivec in Europe) with other chemotherapy drugs to see if there may be a positive benefit in treating mesothelioma patients.

Dr. Gaudino’s research has moved from in vitro experiments with Gleevec alone on mesothelioma cells to mouse studies with Gleevec combined with Alimta (Pemetrexed) and Gleevec combined with Gemcitabine to very positive results in a Phase I clinical trial involving 21 patients with mesothelioma who received a combination of Gemcitabine and Gleevec. Now, Dr. Gaudino is moving to a Phase II trial sponsored by an Italian group where patients with unresectable and difficult to treat malignant mesothelioma will be treated with a combination of Gleevec and Gemcitabine. Dr. Gaudino is excited about this study and optimistic that it will show similar positive results that were obtained in the Phase I study. In another clinical trial, M.D. Anderson Cancer Center in Houston, Texas is currently recruiting participants with malignant mesothelioma for a Phase I study that will use a combination of Cisplatin, Gleevec, and Pemetrexed (Alimta). This study will not only look at the maximum tolerable dose of this combination of these three chemotherapy drugs, but it will also assess the patients’ response to this therapy.

Side Effects

Because Gleevec works to target cancer cells and causes less damage to other cells, the side effects have been less severe than with other chemotherapy drugs. Generally the side effects have been mild and include diarrhea, nausea, muscle pain and rashes. This chemotherapy drug is administered by mouth.