Related Pages Search for Clinical Trials 1 NCI's PDQ® Cancer Clinical Trials Registry. Highlights from ASCO 2002 2 A collection of links to material summarizing some of the important clinical trial results announced at the 2002 annual meeting of the American Society of Clinical Oncology (ASCO). Malignant Mesothelioma Home Page 3 NCI's gateway for information about malignant mesothelioma. Lung Cancer Home Page 4 NCI's gateway for information about lung cancer.

Key Words: chemotherapy, lung cancer, mesothelioma, pemetrexed. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ⁵.)

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.

Glossary Terms

A group of minerals that take the form of tiny fibers. Asbestos has been used as insulation against heat and fire in buildings. Loose asbestos fibers breathed into the lungs can cause several serious diseases, including lung cancer and malignant mesothelioma (cancer found in the lining of the lungs, chest, or abdomen). Asbestos that is swallowed may cause cancer of the gastrointestinal tract.

Treatment with drugs that kill cancer cells.

A drug used to treat many types of cancer. Cisplatin contains the metal platinum. It kills cancer cells by damaging their DNA and stopping them from dividing. Cisplatin is a type of alkylating agent. Also called Platinol.

In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works.

A benign (not cancer) or malignant (cancer) tumor affecting the lining of the chest or abdomen. Exposure to asbestos particles in the air increases the risk of developing malignant mesothelioma.

A drug used alone or with another drug to treat certain types of non-small cell lung cancer and malignant pleural mesothelioma. It is being studied in the treatment of other types of cancer. Pemetrexed disodium blocks DNA synthesis and may kill cancer cells. It is a type of folate antagonist. Also called Alimta and LY231514.

The first step in testing a new treatment in humans. These studies test the best way to give a new treatment (for example, by mouth, intravenous infusion, or injection) and the best dose. The dose is usually increased a little at a time in order to find the highest dose that does not cause harmful side effects. Because little is known about the possible risks and benefits of the treatments being tested, phase I trials usually include only a small number of patients who have not been helped by other treatments.

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

A detailed plan of a scientific or medical experiment, treatment, or procedure. In clinical trials, it states what the study will do, how it will be done, and why it is being done. It explains how many people will be in the study, who is eligible to take part in it, what study drugs or other interventions will be given, what tests will be done and how often, and what information will be collected.

The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiotherapy.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

A treatment plan that specifies the dosage, the schedule, and the duration of treatment.