DMD CLINICAL AND BIOMARKERS: P.139Paediatric use of tamoxifen: good safety profile for boys with Duchenne muscular dystrophy and X-linked myotubular myopathy

Abstract

Duchenne muscular dystrophy (DMD) is caused by the lack of dystrophin, a protein that connects the extracellular matrix to the cytoskeleton in muscle fibres. DMD boys develop progressive muscle wasting, leading to cardiac and respiratory failure and premature death. X-linked myotubular (centronuclear) myopathy (XLMTM) is a very severe myopathy characterized by generalized hypotonia from birth and death of most patients before the age of 2. Our recent preclinical data in mice demonstrated that tamoxifen (a drug used against breast cancer) may be helpful for boys with DMD and XLMTM. TAMDMD, a multicentre, randomized, placebo-controlled, phase 3 clinical trial led by Professor Dirk Fischer (Basel, Switzerland) is being conducted in 5 European countries to assess the efficacy of tamoxifen on >100 DMD boys, of which 16 non-ambulant. Dr Talya Dor (Jerusalem, Israel) is conducting an open-label trial on 30 DMD boys, which suggests that tamoxifen is safe and stops motor decline in DMD boys. A clinical trial with tamoxifen for XLMTM is about to be set in both North America and Europe. Tamoxifen is causing excitement in the Duchenne community and many families are giving the drug to their boys on their own. This goes along with concerns about off-label prescription, quality of alternative sourcing and safety of chronic modulation of the estrogen/androgen balance in boys. In the present work we have reviewed more than 30 papers dealing with paediatric usage of tamoxifen, ranging from recognized off-label application for gynecomastia and McCune Albright syndrome to clinical trials for fibrotic disorders and gliomas and to case reports of compassionate use for a variety of life-threatening diseases. By contrast to women treated for breast cancer, the use of tamoxifen seems not linked to serious adverse events in child. No concern was raised as to sexual development in pre- or peri-pubertal boys. Available data suggest that tamoxifen is safe for boys with DMD or XLMTM.