A medication used to treat some types of cancer may be promising as a lung therapy for people with a disease known as scleroderma (sclair-oh-DER-muh). That's according to a recent trial whose results were released in late May at a conference of the American Thoracic Society.1
A New Role for a Familiar Drug?
The drug is known as cyclophosphamide (sye-kloh-FAHS-fuh-mide), which is sometimes prescribed to treat a number of cancers, as well as lupus in cases in which major organs like the kidneys are affected. It's also sometimes used to treat severe inflammation that hasn't responded to corticosteroids. The medication works by slowing down the immune system so that disease activity can be reduced.2
In this study, cyclophosphamide was tested as a treatment for lung dysfunction in patients with scleroderma, a form of connective tissue disease. In the most serious cases, scleroderma causes severe damage and complications that affect the body's digestive, respiratory, and circulatory systems, and it can be difficult to diagnose since it includes a range of disorders that share symptoms. Those include skin thickening and tightening, hand and feet stiffness, swallowing difficulties, calcium deposits under the skin, dry mucous membranes, skin discoloration, and general fatigue. It's estimated that hundreds of thousands of people in the United States have the disease, and as much as 80 percent are women.3
"Until now, there has been no proven therapy for scleroderma, and 60% to 70% of patients die within 10 years," said Donald Tashkin, MD, a Professor of Medicine at the UCLA, and one of the study's investigators. Half of the deaths from scleroderma are due to lung-related problems, Tashkin added.
First Large Study for This Indication
There have been other studies to test the effectiveness of cyclophosphamide as a scleroderma therapy,4,5 However, those studies tested small numbers of patients. The latest research was the first large, randomized, controlled trial to test the medication's efficacy in scleroderma-related lung disease. (Randomized trials are those in which patients are selected at random to receive an intervention being tested or an intervention with no therapeutic value—a placebo, for example—as a comparison. Controlled trials are those that include a "control", or comparison, group of patients who are given an intervention to compare with the intervention being tested.) Randomized, controlled trials are of higher quality than other studies.
The trial involved 162 patients with lung disease due to scleroderma. Lung function had been significantly impaired and each patient was experiencing shortness of breath. Each of them had been diagnosed with scleroderma at least three years earlier.
Each patient was selected at random to enter one of two groups. One group received doses of cyclophosphamide for a total of one year. The second group was given a placebo as a comparison for the same length of time. Lung dysfunction in five patients progressed to the point at which they had to be switched to the cyclophosphamide group.
Medication Benefits Noted
After one year, Tashkin and his colleagues learned that a significantly greater number of patients receiving cyclophosphamide showed improvement in lung function compared with those in the placebo group. People in the group given the medication also had significantly better breathing ability, and their shortness of breath significantly stabilized more so than those in the group taking the placebo, the researchers noted. Those on the medication also reported having more energy during the study.
Side effects were greater in the cyclophosphamide group; five cases of pneumonia were reported compared to only one case of pneumonia in the group of placebo patients. There were two deaths, each, in both groups during the study. "Nobody died of toxicity from the drug," Tashkin said. "We know cyclophosphamide has toxic effects, but you have to balance the efficacy of the drug against its toxicity. It's a desperate disease, and nothing else has proven effective. We feel the benefits outweigh the risks."
The study was sponsored by the National Institutes of Health.
1. ATS 2005. International Conference of the American Thoracic Society. 2005 May 20-25. San Diego, CA.
2. National Institute of Arthritis and Musculoskeletal and Skin Diseases. National Institutes of Health (NIH). Lupus: A Patient Care Guide for Nurses and Other Health Professionals. Available at: http://www.niams.nih.gov/hi/topics/lupus/lupusguide/chppis16.htm. Accessed May 26, 2005.
3. Scleroderma Research Foundation. What is Scleroderma? Available at: http://www.srfcure.org/srf/patients/whatis.htm. Accessed May 26, 2005.
4. Intravenous cyclophosphamide pulse therapy for the treatment of lung disease associated with scleroderma. Clin Rheumatol 1999;18(6):455-61.
5. Varai G, Earle L, Jimenez SA, Steiner RM, Varga J. A pilot study of intermittent intravenous cyclophosphamide for the treatment of systemic sclerosis associated lung disease. J Rheumatol 1998 Jul;25(7):1325-9.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
