Largest-Yet Mesothelioma Study Shows Survival Benefit with New Drug

Largest-Yet Mesothelioma Study Shows Survival Benefit with New Drug

Researchers with the largest phase III trial to date for mesothelioma, an aggressive cancer affecting the lining of the lung, reported results showing that patients on a new chemotherapy drug regimen live longer and have less pain than those on an older drug. The findings were announced at the annual meeting of the American Society of Clinical Oncology meeting in Orlando, Fla., on May 20, 2002. (NOTE: The final data were subsequently published in the July 15, 2003, issue of the Journal of Clinical Oncology; see the journal abstract).

Pemetrexed (brand name Alimta™) is a novel antifolate, a class of drugs that targets the folic acid metabolic pathway, which effects availability of certain B complex vitamins. The results of the trial show that tumors shrank in 41 percent of patients on pemetrexed in combination with a more commonly used chemotherapy agent called cisplatin. Only 17 percent of patients receiving cisplatin alone experienced tumor shrinkage. Additionally, those on the pemetrexed combination lived nearly three months longer than those on cisplatin alone.

According to lead author, Nicholas J. Vogelzang, M.D., University of Chicago Cancer Research Center, "This is the largest clinical trial ever conducted in this disease and the 25 to 30 percent improvement in survival for patients on the combination therapy is the first time anyone has documented a significant improvement in patients treated for mesothelioma."

Malignant pleural mesothelioma is associated with a history of asbestos exposure in about 70 to 80 percent of all cases and there is no approved or very effective chemotherapy for the disease. Researchers hypothesized that pemetrexed might prove effective in treating this disease because it targets key enzymes (molecules that speed up chemical reactions in the body) thought to play a role in allowing the rapid growth of this tumor.

Early phase I trial results in 11 patients tested with pemetrexed and cisplatin were promising and a definitive randomized phase III trial was developed. Since there are no established therapies for this condition, a standard chemotherapy agent called cisplatin that has shown efficacy in treating other diseases, was used as the control group. The phase III study initially planned to enroll 456 patients from April 1999 to March 2001. However, after enrolling 150 patients, a high rate of severe toxicity and death was associated with the pemetrexed and cisplatin arm of the trial. Elevated levels of homocysteine, a chemical byproduct that results when proteins are broken down in the blood, were found, which provided a basis for redesign of the trial to reduce the dangerous drug side effects.

Two hundred and eighty patients were enrolled to the revised protocol. Using a strategy to reduce drug side effects that has been successful in the past, this new protocol added folic acid to the regimen because pemetrexed as an antifolate agent reduces levels of this important vitamin. Folic acid was given prior to and during the trial, and vitamin B12 was given only during the trial. Both vitamins should boost folic acid levels, reduce homocysteine formation, and hence reduce toxicity to pemetrexed. "We now have a significantly less toxic regimen than the one we started with," said Vogelzang.

Because of the presumed importance of the vitamins to the study, the researchers examined not only the combination therapy versus the single drug therapy, but also looked at the results of patients on the vitamin supplements versus those early enrollees who had not initially received vitamins.

Standard treatment for malignant mesothelioma has been surgery. Surgical treatment rarely results in cure and long-term survival is unusual. Use of radiation therapy and/or chemotherapy following surgery has not improved survival for patients but radiation treatments may alleviate some pain associated with the disease

Lung Cancer Trial Targets Asbestos-Related Disease

Tuesday, July 22, 2008 Source:

Us News And World Report

U.S. News and World Report has recently written about a clinical trial for an experimental mesothelioma treatment that is being conducted at the Mesothelioma Center at New York-Presbyterian Hospital and Columbia University Medical Center.

The trial is investigating the combined use of chemotherapy and radiation in the treatment of pleural mesothelioma, which is a departure from the standard therapies that normally specify some form of curative surgery. Patients who are enrolled in the trial will receive multiple cycles of a chemotherapy regimen consisting of either cisplatin and doxorubicin orcisplatin and pemetrexed (alimta). The latter chemotherapy regimen is the current standard of care in chemotherapy for mesothelioma. All of these patients will receive radiation that is targeted directly at the pleural tissue on the lung.

Although the treatment regimen does not specify curative surgery, it will be available for patients who elect to undergo it. Patients can choose between extrapleural pneumonectomy and pleurectomy/decortication.

The trial is investigating whether this regimen will demonstrate any improvements in overall patient outcome than do the standard therapies.

The Mesothelioma Center at New York-Presbyterian Hospital and Columbia University Medical Center is the only cancer center in the country to offer this therapy.

posted by Belluck & Fox

Chemotherapy is the use of drugs to fight mesothelioma cancer. It is one of the major therapeutic options available for cancer treatment and many of the great success stories in the recent fight against the disease are due to improvements of the chemotherapy agents. To understand how these drugs work we have to understand what cancer is and how it works.

Cancer including mesothelioma is the name of a family of diseases whose fundamental behavior involves the uncontrolled division of cells and the subsequent invasion of these cells into other parts of the body. It's a cellular growth that will never stop without intervention. Although people often speak of cancer as if it were a single entity, it is in fact a number of highly-individualized diseases that all work along these same two principles. For our discussion of chemotherapy, the nature of cell division and replication is the most important area to understand about cancer because this is the domain that chemotherapy targets for treatment.

As we said above, chemotherapy refers to the use of drugs and other chemical (“chemo” is a derivative of “chemical”) agents to fight cancer. Most traditional chemotherapy drugs fight cancer by inhibiting the process of cell division (mitosis) among rapidly dividing cells, although some drugs may work along a different framework. There are drugs which enhance the apoptotic process by which malformed cells are removed from the body and others that target different phases in the cell cycle.

In all cases, successful chemotherapy cures the body of cancer by arresting the production of new cancer cells and killing off whatever malignant structures remain. As such, chemotherapy drugs are considered cytotoxic agents which means drugs that kill cells.

But one of the biggest problems with chemotherapy is its lack-of-specificity for cancer cells. Chemotherapy is considered a broad-scope treatment because it attacks all rapidly dividing cells—not just cancer cells. This is the primary reason for the side effects that are commonly associated with it, such as anemia, digestive disorders and hair loss. The natural activity of bone marrow cells, as is also the case with the cells that control the growth of hair follicles and those that line the digestive track, is also characterized by rapid division, so they, too, are affected by chemotherapy. Science is only now beginning to map the different internal structures between normal cells and cancerous ones, so traditional cancer treatments, such as chemotherapy, have been unable to distinguish between these cell types in meaningful ways. Even as recent years have shown a great increase in the overall efficacy of many chemotherapy agents—as well as a reduction in the severity of many of the side effects associated with treatment—chemotherapy is still considered a systemic therapy because of the wide scope of cells that are subject to its cytotoxic effects.

Within the standard framework of cancer treatments, chemotherapy is considered the most effective single modality for the treatment of mesothelioma and is likely to be the most commonly deployed treatment as well. Most people who are diagnosed with the disease in its later stages are not eligible for “curative” surgeries, so chemotherapy becomes their best chance at extending life. For patients who are diagnosed in an earlier stage or are otherwise candidates for surgery, chemotherapy is likely to be used along with surgery and radiation therapy.

Even though chemotherapy can be effective at extending life, it is not a curative treatment for the disease because mesothelioma has not cure at this time. Even as advancements in our treatments have led to longer survival times and better control of patient symptoms, the disease continues to resist long-term management and survival.