Japan Study Find Standard Chemotherapy Still Best Hope for Mesothelioma

The long-standing chemotherapy combination of cisplatin and pemetrexed will remain the front-line treatment regimen for mesothelioma patients in the foreseeable future, despite recent efforts to develop newer and more effective drugs.

Nothing better has emerged.

Researchers at the Shizuoka Cancer Center and Juntendo University in Japan recently concluded that the cisplatin/pemetrexed (Alimta) combination remains the best choice.

"It should continue to be the standard, front-line chemotherapeutic regimen for inoperable MPM (malignant pleural mesothelioma)," wrote the authors of the March study, published in Respiratory Investigation.

The medications are most effective with asbestos-related cancer when used in conjunction with surgery and radiation, but more often they are used alone with patients who are not surgical candidates because the cancer already has metastasized.

Although Alimta was not approved by the U.S. Food and Drug Administration (FDA) until 2004, it has been used since the mid-1990s after it was granted an early compassionate-use exception. It was the first medication specifically approved for the treatment of mesothelioma. It has been used for almost two decades in combination with cisplatin, and both drugs increase the effectiveness of the other.

Study Compares Chemotherapy Combinations

Gemcitabine, carboplatin, doxorubicin and vinorelbine are other chemotherapy drugs used, but often found to be less successful. More are being tested in clinical trials.

The recent study in Japan compared the combination of gemcitabine (Gemzar) and cisplatin with the combination of pemetrexed (Alimta) and cisplatin. Both Gemzar and Alimta, the two most widely used drugs, are marketed by Eli Lilly and Company and used with a variety of cancers.

The study included 30 MPM patients between 2002 and 2011, including 17 with the cisplatin/Alimta combination, and 13 with the Gemzar/cisplatin combination. Doctors analyzed the patients' medical charts for antitumor efficacy and drug toxicity.

The response rate for cisplatin/Alimta was 35 percent, but only 15 percent for Gemzar/cisplatin. The progression-free survival rate was 215 days for Alimta and 142 days for Gemzar. The median overall survival rate was 597 days for Alimta patients and 306 days for Gemzar patients.

Researchers found hematological toxicities, particularly neutropenia and thrombocytopenia, were more severe and more frequent with those in the Gemzar/cisplatin group.

Powerful Drugs

The study was in response to previous trials that showed an improvement in both response and survival rates when cisplatin (approved by the FDA in 1978) was supplemented by either Alimta or Gemzar. The study was the first to compare the two separate combinations.

Cisplatin has been used for a wide variety of cancers, both as a single-agent treatment and in conjunction with other chemotherapy drugs. As a single agent for mesothelioma, the response rate has been less than 15 percent.

Chemotherapy has been the most widely used category of drugs for mesothelioma patients, but others are growing in use as doctors and patients seek more effective treatment options.

Immunotherapy, targeted therapy, photosensitizing and anti-angiogenesis drugs also are used on various levels. Chemotherapy agents are powerful, but they attack both cancer and healthy cells, causing a variety of side effects.

Targeted therapy drugs, such as NGR-hTNF, are designed to target specific molecular alternations in cancer cells. Immunotherapy drugs are designed to help the body's immune system better recognize and attack the cancer cells. Photosensitizing drugs are constructed to make the cancer cells easier targets for particular beams of light to destroy. Anti-angiogenesis drugs help starve cancer cells and prevent them from multiplying. The newer categories of drugs are less toxic.

While the newer types of drugs have shown considerable promise, they remain in clinical trial phases, out of reach to many doctors and patients.

Researchers in Japan concede the limitations of their retrospective study â€" particularly the limited number of patients â€" but do assert the cisplatin/Alimta combination remains the best option available today.

Author: Tim Povtak

Tim Povtak is an award-winning writer with more than 30 years of reporting national and international news. His most recent experience is in researching and writing about asbestos litigation issues and asbestos-related conditions like mesothelioma.

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Study: Palliative Chemotherapy Not Meeting Patient Expectations

Mesothelioma patients and their caregivers should take a closer look and decide on their priorities before starting palliative care chemotherapy, which has disappointed many in the past, according to a recent study.

Although it is designed to prolong survival and ease symptoms for terminal cancer patients, palliative care chemotherapy often ends with a diminished quality of life, more invasive, late-stage medical procedures, and dying in a less than desirable setting.

Researchers also have found a startling gap between the type of end-of-life cancer care patients wanted, and what they actually received, according to a collaborative study of palliative care chemotherapy published recently in the British Medical Journal (BMJ). Weill Cornell Medical College, Dana-Farber Cancer Institute and Harvard Medical School officials conducted the study.

"It's hard to see in this data much of a silver lining to palliative chemotherapy for patients in the terminal stage of their cancer," said Dr. Holly Prigerson, professor of medicine at Cornell. "This study is the first step in proving evidence that specifically demonstrates what negative outcomes may result."

Palliative Chemotherapy Shortens Hospice Care

During a six-year period, investigators analyzed data from 386 terminally ill patients who were part of Coping with Cancer, a federally funded study. The American Society of Clinical Oncology recently identified palliative care chemotherapy as one of the practices that, if stopped, could improve patient care and reduce costs.

This study found the use of palliative chemotherapy was associated with late hospice referrals and higher rates of cardiopulmonary resuscitation and mechanical ventilation in the last week of life, but not increased survival. Patients also were less likely to die at home and more likely to die in intensive care, compared with those who did not receive palliative chemotherapy.

"Palliative care was intended to prolong life and ease symptom burden, but it might not do either," Prigerson said. "It might, in fact, make things worse. Patients may want [chemotherapy] if it brings hope, but it should not be false hope. They should have data from studies like this, and know what the potential costs are when they are that advanced in the illness."

Fewer Die at Home After Chemotherapy

According to the study, 47 percent of the patients who received chemotherapy died at home, compared with 66 percent of the patients who did not receive palliative chemotherapy. Only 2 percent of the patients not receiving therapy died in intensive care, compared with 11 percent of those receiving palliative chemotherapy.

The study also found that 54 percent of those receiving chemotherapy were referred late (in the last week of life) to hospice care, which is designed to provide both comfort and emotional support for patients. Only 37 percent of those not receiving chemotherapy were referred late to hospice care.

"We often wait until patients stop chemotherapy before asking them about where and how they want to die," said Dr. Alexi Wright, medical oncologist at Dana-Faber. "But this study shows we need to ask patients about their preferences while they are receiving chemotherapy to ensure they receive the kind of care they want near death."

Both researchers agreed there often is a misunderstanding of the consequences and purpose of palliative chemotherapy. The study followed each patient until they died. Afterward, researchers interviewed the caregivers about each patient's care, where the patient had wanted to die, and then compared those answers to medical charts detailing the last week of life.

"Until now, there hasn't been evidence of harmful effects of palliative chemotherapy in the last few months of life," Prigerson said. "Additional studies are needed to confirm these troubling findings."

Author: Tim Povtak

Tim Povtak is an award-winning writer with more than 30 years of reporting national and international news. His most recent experience is in researching and writing about asbestos litigation issues and asbestos-related conditions like mesothelioma.

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