Mesothelioma Helping

Combination drug treatment helps beat mesothelioma

Medical Studies/Trials

Monday, 12-Feb-2007 - People with mesothelioma - a form of cancer associated with asbestos exposure - have a higher survival rate when treated with a combination of two cancer drugs, a large multicenter study finds.

Mesothelioma, a rare but aggressive form of cancer that occurs in the lining of the lungs, heart and abdomen, is associated with exposure to asbestos. There is no known cure.

In the study, patients receiving pemetrexed and cisplatin - along with the vitamin supplements folic acid and B12 - survived nearly three months longer than patients getting cisplatin alone.

Researchers led by John Green, M.D., at the Clatterbridge Center for Oncology in England, reviewed a study of 448 patients with advanced mesothelioma who were treated with either the single drug or the combination.

"Pemetrexed used in combination with cisplatin significantly increases the length of survival, when compared with cisplatin alone," the researchers say. "Further research is needed into the optimum treatment regimen for pleural mesothelioma."

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

The researchers examined data from a clinical trial of 20 treatment centers in Europe, the Americas, Australia and Asia. Eighty-one percent of the patients were men, with an average age of 61. Patients who received the combination treatment survived an average 2.8 months longer.

Patients receiving both medications also reported improved quality of life in terms of fatigue, loss of appetite, pain and cough.

During the early stages of the trial, patients receiving pemetrexed had serious symptoms of toxicity, including drug-related death. Other side effects included blood cell abnormalities, nausea and diarrhea, which decreased in both incidence and severity after the vitamins were added to the treatment. People who work trades such as shipbuilding, railway engineering, construction work and asbestos manufacture have higher rates of mesothelioma than the general public. The cancer may take 10 to 60 years to develop, and the risk does not diminish after exposure to asbestos has stopped. Family members of people exposed to asbestos at work also have an increased risk of developing mesothelioma from asbestos fibers carried home on the clothes of the people they live with.

Daniel Baram, M.D., a pulmonologist at the Lung Cancer Evaluation Center at the State University of New York, said, "Most cases [of mesothelioma] are still from pre-OSHA workplace improvements. I suspect that modern asbestos abatement precautions will avoid most, if not all, future cases. The latency is over 30 years, so we are still diagnosing cases with exposure during World War II and the '40s and '50s."

Mesothelioma is difficult to diagnose, Green said, because "there is a lag of many years between exposure and asbestosis, which is a nonmalignant condition, and a greater lag before the development of overt malignancy."

"There is no way of diagnosing the premalignant phase during the latent period of 15 to 20 years," Green added. "Many of these patients smoke and are in economically disadvantaged communities. Many individuals have moved away from heavy industries and may not admit or know they were exposed to asbestos as young men, with similar issues for their partners."

According to the U.S. Environmental Protection Agency, 10 percent to 15 percent of schools and other public buildings in the United States contain asbestos insulation.

Although safety measures for working with asbestos have been in place since the 1970s, mesothelioma is projected to account for 65,000 deaths between 2001 and 2050 worldwide, peaking between 2012 and 2015, according to background information in the review.

It is a personal matter as to whether the survival increase for patients receiving the two drugs is worthwhile, Baram said. "It depends in large part on the patient. A 2.8-month mean survival increase means that some patients may get even more than that, though some people will get less. Many, if not most, patients when faced with a disease with a very bad prognosis are often willing to undergo aggressive therapy, although the toxicity is serious and potentially life-threatening."

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Mesothelioma and Molecular Pathways

"Slow but definite progress" furthers understanding of mesothelioma: Molecular signaling pathways provide clues to targeted therapies by Jeni Baker

April 26, 2007 - Mesothelioma Research - If you're reading this article, you probably already know something about malignant mesothelioma, a particularly insidious form of cancer. What you may not know is that the scientific community is making important strides toward understanding how the disease works on a molecular level - and ultimately, toward developing therapies that treat it.

A recently published review* looks at some of the molecular signaling pathways currently being investigated.

The challenge of developing disease-specific treatments

The goal is to develop more - and more effective - treatments, says co-author Dan J. Raz, MD, of the University of California, San Francisco's Division of Thoracic Surgery.

"The options for mesothelioma patients have primarily been surgery, conventional chemotherapy, and radiation therapy," Raz says. "But even when a combination of treatments is used, the outcomes aren't great."

While several drugs have been approved for treating mesothelioma, there aren't a lot - largely because researchers simply haven't been able to conduct many clinical drug trials.

This is in part because, with some 5,000 Americans diagnosed with the disease annually, mesothelioma is fairly uncommon compared with other cancers. This factor, combined with mesothelioma's typically swift progression, has made it difficult to enroll enough people in drug studies.

Another obstacle has been the large spectrum of disease. "When patients present with mesothelioma, we often don't know how long they've had it, which can make it difficult to differentiate people with different levels of disease, and to know what the best treatment options might be," Raz says.

So instead of waiting for drugs to be approved for other cancers to conduct clinical trials for their use in mesothelioma - which is how it currently works - researchers are striving to develop drugs specifically for the disease.

Which brings us back to the study of its molecular signaling pathways.

Pathways to understanding

Clinical trials of several angiogenesis drugs (those that target the blood vessels that fuel tumor growth) known to be effective for other diseases suggest that two signaling pathways examined in the article - vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) - can be disrupted by these drugs.

The review also looked at the Wnt pathway, which - because it is believed to play an important role in activating mesothelioma stem cells - also shows promise as a treatment target. By learning how to target problems in this initiating pathway, scientists may discover ways to essentially nip mesothelioma in the bud, Raz says. Several Wnt antibodies will soon enter clinical trials.

Other signaling pathways currently being studied include P53 and pRB, as well as the BCL-2 family. Also significant to the molecular makeup of mesothelioma, these pathways hold valuable clues for developing effective disease-specific therapies.

In the meantime, a number of trials for drugs developed for other cancers are underway, says Raz, and many new angiogenesis therapies are in the pipeline.

Another promising avenue - for countless medical conditions, not just cancer - is genomic medicine, of which knowledge is growing every day.

"By learning about the genetic patterns of individuals, we'll eventually be able to know how someone's genes interact with the biology of tumors, which signaling pathways play which roles in different people, and how patients will respond to different therapies," Raz says. "Genetic medicine and drug development go hand in hand, and most people in the scientific community agree that this is the future of medical treatment."

Raz encourages patients diagnosed with mesothelioma to look into clinical trials, and to seek treatment from physicians with specialized training and experience, at centers with recognized mesothelioma programs.

A growing number of centers fit the bill - UCSF, Brigham and Women's Hospital, and Memorial Sloan Kettering Cancer Center, to name a few - which translates into more treatment options for patients.

"This is a very exciting time for advances in mesothelioma, and slow but definite progress is being made," Raz says. "The scientific community is starting to understand a lot more about the biology of this terrible disease, which means that more targeted therapies are being introduced that could potentially help people."


* Lee AY, Raz DJ, He B, Jablons DM, Update on the Molecular Biology of Malignant Mesothelioma. Cancer, 2007 Mar 8:109(8):1454-1461

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