The results of the study have been published in the June 22 issue of the New England Journal of Medicine, which has revealed that this immunosuppressive drug used in treatment of cancer could slightly improve lung function as well as the quality of life for people with scleroderma-related lung disease.
According to 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 'Scleroderma can be a devastating disease for which there has been no effective therapy.'
'In our study, we found that active treatment with cyclophosphamide had a significant -- statistically and clinically -- meaningful and favorable impact on disease progression.'
Scleroderma, an autoimmune disease causes thickening of the skin, and may even involve other areas of the body such as the lungs, heart and kidneys. According to the Scleroderma Foundation 300,000 Americans have scleroderma. One-third or less of scleroderma affected-patients have widespread disease, while the remaining two-thirds mainly suffer from skin symptoms.
If the lungs are affected scarring takes place with restricted breathing because the lungs can no longer expand as they should. Doctors measure breathing capacity with a device that assesses forced vital capacity (FVC). When FVC is 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.
The mortality rate is high because of the non availability of any effective treatment. Past research and case reports had suggested that cyclophosphamide (brand name Cytoxan) might be an effective drug for scleroderma lung disease.
Tashkin and his colleagues tested this idea on some 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.
Follow-up after 12 months revealed the adjusted FVC value to be approximately 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 cyclophosphamide has significant side effects. It can increase the risk of serious infections such as pneumonia, affect the bone marrow and platelet production, and cause bleeding in the bladder. Long-term use of the drug has also been associated with an increased risk of bladder cancer.
Drs. Fernando Martinez and W. Joseph McCune, from the University of Michigan Health System, in a related editorial wrote that cyclophosphamide is 'arguably the most toxic immunosuppressive agent currently used to treat lung disease.'
But as Martinez said, there could 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.
Martinez concluded that this medication is one that patients and doctors have to discuss and decide on a case-by-case basis and decide if the potential benefit is worth the risk to that particular patient.