Cancer Drug May Fight Scleroderma Lung Disease

But Cytoxan's benefits may not always outweigh the risks, researchers say

WEDNESDAY, June 21, 2006 (HealthDay News) -- An immune-suppressing drug that's primarily used to treat cancer may also have a role in the treatment of lung disease associated with scleroderma.

That's the conclusion of a new study in the June 22 issue of the New England Journal of Medicine that found that treatment with the cancer medication cyclophosphamide could slightly improve lung function and quality of life for people with scleroderma-related lung disease.

"Scleroderma can be a devastating disease for which there has been no effective therapy," said the study's lead author, Dr. Donald Tashkin, a professor of medicine in the pulmonary and critical care division at the David Geffen School of Medicine at the University of California, Los Angeles.

But, he said, "In our study, we found that active treatment with cyclophosphamide had a significant -- statistically and clinically -- meaningful and favorable impact on disease progression."

Scleroderma is an autoimmune disease that causes scarring or thickening of the skin, and sometimes involves other areas of the body, including the lungs, heart and kidneys. About 300,000 Americans have scleroderma, according to the Scleroderma Foundation. One-third or less of those affected have widespread disease, while the remaining two-thirds primarily have skin symptoms.

If the disease affects the lungs, causing scarring, breathing becomes restricted because the lungs can no longer expand as they should. To measure breathing capability, doctors use a device that assesses forced vital capacity (FVC). In people with an FVC of less than 50 percent of the expected reading, the 10-year mortality rate from scleroderma-related lung disease is about 42 percent, according to the study.

One reason the mortality rate is so high is that there's no effective treatment available. Past research and case reports had suggested that cyclophosphamide (brand name Cytoxan) might be an effective drug for scleroderma lung disease.

To test that idea, Tashkin and his colleagues recruited 158 patients from 13 centers throughout the United States. FVC values at the start of the study were between 45 percent and 85 percent of the predicted value.

The patients were randomly assigned to receive either a year of treatment with cyclophosphamide or a placebo. One hundred and forty-five people completed at least six months of the trial.

After 12 months, the adjusted FVC value was close to 3 percent better in the cyclophosphamide group than for the placebo group. Lung capacity decreased by over 4 percent for the placebo group, while the treated group stayed the same. Tashkin said that those who received treatment also reported a better quality of life than those in the placebo group.

However, the news isn't all good, because cyclophosphamide has significant side effects. It can affect the bone marrow and platelet production, increase the risk of serious infections such as pneumonia, and cause bleeding in the bladder. Long-term use of the drug has also been associated with an increased risk of bladder cancer.

In a related editorial, Drs. Fernando Martinez and W. Joseph McCune, from the University of Michigan Health System, wrote that cyclophosphamide is "arguably the most toxic immunosuppressive agent currently used to treat autoimmune diseases."

Still, Martinez said, there may be patients for which the benefits of the drug outweigh the risks.

"In patients who clearly have demonstrated progression of disease or who have more severe disease, it may be reasonable to consider cyclophosphamide early on," he said.

"This is clearly a positive study. There's clearly a benefit, though not a dramatic benefit, and there is the potential for quite a bit of toxicity. The long-term toxicity remains unclear," said Martinez.

Tashkin said that these findings "suggest that the benefits of treatment outweigh the risks."

Martinez said this medication, like so many others, is one that patients and doctors have to discuss and decide on a case-by-case basis if the potential benefit is worth the risk to that particular patient.

In another study in the same issue of the journal, Italian researchers reported that they had found a blood marker associated with scleroderma that may also have a causal effect. The marker is platelet-derived growth factor (PDGF), and this finding may help researchers further understand the mechanisms behind the disease, which could eventually help lead to targeted therapies to treat scleroderma.

More information

To learn more about scleroderma, visit the Scleroderma Foundation.

SOURCES: Donald Tashkin, M.D., professor of medicine, pulmonary and critical care division, David Geffen School of Medicine, University of California, Los Angeles; Fernando Martinez, M.D., professor of internal medicine, division of pulmonary and critical care medicine, University of Michigan Health System, Ann Arbor; June 22, 2006, New England Journal of Medicine
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