A medication prescribed to treat some forms of cancer, lupus, and inflammation when corticosteroids fail, may also be effective against a connective tissue disease associated with pulmonary hypertension (PH) known as scleroderma.
Researchers detailed their discovery this past May at the annual meeting of the American Thoracic Society in San Diego.1
The drug is known as cyclophosphamide (Cytoxan, CTX), and is sometimes prescribed to treat cancers like lymphoma, leukemia or multiple myeloma. It's also used as therapy for people with lupus when major organs like the kidneys are affected, as well as an anti-inflammatory in cases in which patients aren't responding to the first-line treatment, corticosteroids. Cyclophosphamide is also used to ease immune system activity in lupus.2
Scleroderma and Fibrosis: Common Features
Scleroderma is not actually a single disease, but describes a group of related disorders, all of which are manifested by the same symptoms. This, however, makes diagnosis difficult. Scleroderma shares the same features as fibrosis—an excessive accumulation of tissue and inflammation.3
Pain, ranging from uncomfortable to debilitating, is a common symptom. Other symptoms:
• General fatigue
• Joint or bone aches
• Hand and feet stiffness
• Skin discoloration
• Swallowing difficulties
• Skin thickening and tightness
• Dry mucous membranes
• Calcium deposits
• Raynaud's phenomenon (A bluish coloration of the skin as a response to cold or stress).
Scleroderma is not only a rheumatic disease, but also involves the blood vessels. Inflammation in these vessels narrows them, subsequently increasing blood pressure and potentially damaging the vessels. Destruction of much smaller arteries may also occur. In fact, pulmonary arterial hypertension is common in people with scleroderma, and is considered a leading cause of death. As a result, or in conjunction with, scleroderma, fibrosis (scarring) occurs. This can place added burdens on the heart and lungs, diminishing their function.3 Since multiple areas of the body are affected, the disease is sometimes referred to as systemic sclerosis.
The cause of scleroderma is not known, but there has been evidence of a genetic predisposition associated with the illness.4
Few Therapeutic Options
"Until now, there has been no proven therapy for scleroderma, and 60 percent to 70 percent of patients die within 10 years," said Donald Tashkin, MD, a professor of Medicine at the David Geffen School of Medicine at UCLA, who headed the study released at the medical conference.
According to Tashkin and his team, approximately 150,000 Americans have scleroderma and three times as many women develop the disease.
Though medical experts have suggested in the past that cyclophosphamide may be efficacious against scleroderma,5 the study by Tashkin and his fellow researchers was the largest randomized, clinical trial to date to test the drug's effectiveness.
Cyclophosphamide v Placebo
Tashkin and his colleagues recruited 162 patients into their study. Each of them had been diagnosed with scleroderma, which had significantly impaired their lung function, and caused significant shortness-of-breath. Each patient had had the disease for at least three years, and only those with active lung inflammation were included, since they would be more likely to respond to an anti-inflammatory.
Tashkin and his colleagues then assigned each patient at random to a group that received cyclophosphamide for a year, or a group that received a placebo—an intervention that has no therapeutic value, included as a comparison to the drug being tested—for the same time period.
Drug Caused Greater Improvement
At the end of the trial, a significantly greater proportion of patients taking cyclophosphamide showed improvement in lung function compared with those given only a placebo. Patients on the medication also had significantly more improvement in their shortness-of-breath, or in the very least, it stabilized. In fact, the lung function of five patients in the placebo group had deteriorated so significantly that researchers began giving them cyclophosphamide instead.
The patients in the medication group also reported better functional ability than those taking only a placebo. They also mentioned having more energy and pep while taking the drug.
On the downside, more side effects were reported in the group taking the drug, such as five cases of pneumonia. The number of deaths was equivalent—two patients in either group died. However, "nobody died of toxicity from the drug," Tashkin stated. "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," he said. "We feel the benefits outweigh the risks."
Now that this clinical trial has concluded, Tashkin and his co-investigators are hoping to study the safety and effectiveness of a combination of cyclophosphamide and another medication designed to fight the effects of lung scarring caused by scleroderma. "We found favorable effects with cyclophosphamide, but we want to do better," he said.
1. ATS 2005. The International Conference of the American Thoracic Society. 2005 May 20-25.
2. National Institute of Arthritis and Musculoskeletal and Skin Diseases. National Institutes of Health (NIH). Available at: http://www.niams.nih.gov/hi/topics/lupus/lupusguide/chppis16.htm. Accessed September 15, 2005.
3. Scleroderma Research Foundation. What is Scleroderma? Available at: http://www.srfcure.org/srf/patients/whatis.htm. Accessed September 15, 2005.
4. Herrick AL, Worthington J. Genetic epidemiology: systemic sclerosis. Arthritis Res 2002;4(3):165-8. Epub 2002 Jan 16.
5. White B. Evaluation and management of pulmonary fibrosis in scleroderma. Curr Rheumatol Rep 2002 Apr;4(2):108-12.
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.
