ON THE CURRENT MANAGEMENT OF OSTEOSARCOMA - A CRITICAL-EVALUATION ANDA PROPOSAL FOR A MODIFIED TREATMENT STRATEGY

The current management of osteosarcoma (OS) is critically reviewed and a modified treatment strategy is put forward for discussion. The over all treatment results in high-grade OS are less impressive than widely assumed. Whereas in 'classical OS' survival has indeed increased duri ng the past decades from approximately 20% to at least 60%, in other s ubgroups, comprising more than 40% of the entire OS population, the pr ognosis has been only modestly improved. Today still more than half of an unselected OS population eventually succumbs to the disease despit e the current multimodal primary treatments as well as second-line che motherapy and surgical metastasectomy(ies). Analysis of the reported r esults indicates that a survival plateau of approximately 60% can be a chieved by several different drug combinations. The inclusion of addit ional drugs and treatment with complex combinations to all patients ha s not yielded a convincing survival benefit. These expensive regimens overtreat a large number of patients, namely those who could have been cured by the previous less drastic regimens, and it increases the acu te and delayed side-effect. Toxic deaths occur and life-threatening si de-effects are not infrequent, necessitating interruption of the treat ment or reduction in the dose intensity. A possible marginal early sur vival benefit may well be offset by late side-effects. For the above r easons, we propose an alternative, risk-adapted, treatment strategy, t o retain the present results at a lower price in terms of acute toxici ty and late morbidity. It is suggested that all patients with classica l OS should be treated pre-operatively with optimal doses of only the two most active agents, methotrexate and doxorubicin. This presumably is sufficient in the majority of these patients. The most toxic treatm ent involving additional anticancer agents should be reserved for high -risk and relapsing patients, i.e. for situations where drastic measur es are necessary and warranted. An important consideration is that rel apsing patients are likely to benefit in particular from drugs to whic h they have not been previously exposed. (C) 1997 Elsevier Science Ltd .