Toronto (March. 15, 2011) - For the first time, researchers at Toronto General Hospital, University Health Network (UHN), University of Cincinnati and others have found that a drug used in the treatment of cancer and transplants also stabilizes lung function in patients with lymphangioleiomyomatosis (LAM), a rare, progressive disease that affects mainly young women.

In their ground-breaking research, 13 centres in the US, Japan and Canada have shown that women with moderately severe LAM who received the drug sirolimus for one year had no decline in lung function in contrast to similar women on placebo who showed significant lung function decline.


"For patients, this means there is hope for the first time, because they now have a treatment that can prevent the loss of lung function for at least one year, and potentially even longer," said Dr. Lianne Singer, Medical Director, Toronto Lung Transplant Program at Toronto General Hospital (TGH) and the principal investigator of the sole Canadian site in the study.

The Multicentre International LAM Efficacy of Sirolimus (MILES) trial was the first randomized, controlled study designed to test a therapy for this illness, in which patients progressively lose lung function, and many die from lung failure. There is no cure for this disease, and the only treatment is a lung transplant. It is estimated that there are up to 100 women in Canada who suffer from this illness.

Results from the study called, "Efficacy and Safety of Sirolimus in Lymphangioleiomyomatosis (LAM)", are reported in the March 16, 2011, online edition of the New England Journal of Medicine.

The trial had two stages – a 12 month, randomized, double-blind trial that compared sirolimus (also called rapamycin) with placebo, followed by a year of observation in which none of the patients received the treatment. The primary outcome measure was a standard breathing test which measures the change in the volume of air that a person with fully inflated lungs can blow out in one second. This was measured repeatedly in both groups and the differences were recorded.

Results showed that lung function of the sirolimus group of 46 women stabilized in the one year of treatment, in contrast to the 43 patients in the placebo group whose lung function deteriorated. This latter group showed a 12 ml per month decline – which is more than half a cup of air in one year.

"That kind of decline continuing over time could result in more shortness of breath, more limited daily activities and an increased need for oxygen", said Dr. Singer, who is also Assistant Professor of Medicine, University of Toronto.

Kelly Tate, 48, was diagnosed seven years ago with LAM. Kelly leads a busy life, with four children, three dogs, three cats and a bunny, a luscious greenhouse and a comfortable home in the country. Kelly was glad to be in the study because she wanted to be "part of a discovery for the next group of women who have this disease."

Kelly, who was in the treatment arm of the study, noted that on the medication, her breathing was stronger and that she could walk up 12 steps easily, without the boost of extra oxygen.

"I want to hang on to my lungs as long as I can," she said cheerfully. "Who knows what else they might discover in the future…and I still have lots of flowers to grow!"

Dr. Singer noted that additional trials are needed to determine the dose and safety of sirolimus over a long-term treatment period.

The study also showed some reductions in symptoms and improvements in quality of life in the sirolimus group of patients. However, in the observation period, when treatment was stopped, the decline in lung function resumed in the sirolimus group and paralleled that in the placebo group. Adverse events were more common with sirolimus, but the frequency of serious adverse events did not differ significantly between the groups.

The clinical trial was funded by the NIH Office of Rare Disease Research, the US Food and Drug Administration, the LAM Foundation, the Japanese Ministry of Health, Labour and Welfare, the Canadian Institutes of Health Research, Cincinnati Children's Hospital, University of Cincinnati, the Tuberous Sclerosis Alliance and Vi and John Adler and the Adler Foundation.


Pfizer, maker of sirolimus, provided the drug and financial support, but had no role in the study design, conduct, analysis or reporting of the data.

About Toronto General Hospital

Toronto General Hospital is a partner in the University Health Network, along with the Toronto Western Hospital and the Princess Margaret Hospital. These research hospitals are affiliated with the University of Toronto. Toronto General Hospital is a national and international source for research, education and patient care, and is recognized internationally for its innovations in transplantation, surgical innovation, infectious diseases, diabetes and genomic medicine. The lung transplant program is one of the largest in the world, performing about 100 transplants a year. Both the pulmonary and transplant programs are renowned worldwide for their innovation and comprehensiveness in treating patients with severe and complex lung diseases.

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