Phase II new drug trials in soft tissue sarcomas

As stated in chapter 6, doxorubicin remains the most active single chemother-apeutic agent in the treatment of metastatic soft tissue sarcomas. Approximately 25% of the patients treated with Doxorubicin will have a clinical response [1–5]. This was demonstrated with an interval of ten years in the USA [2] and Europe [4, 5]. A steep dose response curve documented in several series [2, 5] led to the recommendation to give the drug in a dose just tolerated by the bone marrow. Further studies with combinations in which DTIC, Vincristine, Cyclophosphamide and/or Actinomycin D were included, depicted, however not in randomized trials, a survival advantage for responders to the combinations. Median survivals of 15 months versus 8 months were reported [6–8]. Alterations in the basic CYVADIC regimen (Table 1) have been conducted in an effort to increase response and survival and to reduce toxicity [9–11] but offered no advantage over the conventional 5-day regimen. The last study [11] however revealed that the performance status of the patients was the major prognostic determinant for response. This could also explain the wide differences in response rates reported in several series. The only progress with the combinations was the observation that in a subgroup of patients the application of surgery could render these patients free of disease and a survival advantage was observed [12]. Considering this minimal advantage with the combination it is not surprising that several cooperative groups — ECOG and EORTC — have continued to use single-agent Adriamycin as their ‘standard’ of comparison, for first line treatment.