New agents in the treatment of soft-tissue sarcomas

The list of agents with significant activity in soft-tissue sarcomas is very short and arguably, only includes doxorubicin and ifosfamide. Several other agents such as dacarbazine, cisplatin and etoposide, to name but a few, have marginal activity and are sometimes used in combination regimes. The need for the identification of new agents with activity against this disease is therefore paramount. Soft-tissue sarcomas are very rare and diverse and as a result, new drug trials are few and far fetched. The conventionally conducted Phase II trials, which include all histologies of soft-tissue sarcomas, run the risk of an inadequate assessment of the new drug in individual subsets, which may have variable biological behaviours. On the other hand, histology-specific Phase II trials are fraught with the problems of length due to the infrequent nature of the disease and the considerable running costs. The end result is that in this era of cost-containment, soft-tissue sarcomas are not high on the priority list of many funding agencies, thus explaining the lack of any significant progress over the past two decades. Efforts at optimising the dose intensity and schedule of administration of doxorubicin and ifosfamide, have resulted in superior activity when combined and improvement in the survival of patients with high-risk localised disease. However, efforts at identifying new agents with adequate activity have not had much success. Patients, physicians and pharmaceutical industries must be encouraged to participate in multidisciplinary clinical trials in order to improve cure rates for patients with advanced disease.