Role of Doxorubicin in rhabdomyosarcoma: is the answer knowable?

The role of doxorubicin in treatment of rhabdomyosarcoma (RMS) has been controversial for 30 years. Despite its known activity in RMS, because of its risk of cardiotoxicity, its use is not justified in low-risk patients who have an excellent chance of cure with vincristine, actinomycin with or without cyclophosphamide, and primary tumor treatment. For patients with intermediate and high risks, the risk/benefit ratio must be carefully considered. In addition, the peak incidence of RMS is in toddlers, with whom the risk of cardiotoxicity of anthracyclines is higher. A number of trials both in North America and Europe, which are reviewed in this article, have investigated the role of doxorubicin in RMS, with no conclusive outcomes. In addition, differences in risk-group assignment on two sides of the Atlantic further complicate comparisons and analyses. The current European EpSSG 2005 study for high-risk RMS (by the European definition) may come closest to giving an answer to the role of doxorubicin in RMS.