Only few cytostatic drugs are used for the treatment of adult soft-tissue sarcoma, with adriamycin and ifosfamide being the most active agents achieving response rates of 20-35%. In addition, for dacarbazine and cyclophosphamide responses have been reported in 10-20% of patients. A dose-response relationship for adriamycin has been suggested based on results from phase II and III studies. 70 mg/m2 single-agent adriamycin every 3 weeks is considered as standard anthracycline treatment for metastatic soft-tissue sarcomas; higher doses have been associated with cardiac and skin toxicity. Clinical studies have also indicated a dose-response relationship for ifosfamide. Tumour responses to high-dose ifosfamide regimens ( > 5 g/m2, given as continuous intravenous infusion) have been achieved in patients relapsing after or resistant to ifosfamide-based regimens at standard doses. Haematopoietic growth factors, particularly G-CSF and GM-CSF, seem to reduce the number of infectious episodes following standard-dose chemotherapy and may allow the application of full doses of chemotherapy cycles on schedule. However, only moderate dose escalations of chemotherapy regimens by factors 1.2-1.4 were possible with the use of G-CSF or GM-CSF due to severe mucositis and cumulative thrombocytopenia. Studies with ultra-high doses of melphalan, ifosfamide or ifosfamide and either carboplatin or adriamycin followed by autologous bone marrow rescue or peripheral blood progenitor cells and growth factors have demonstrated that instead of myelosuppression other toxicities will be dose-limiting. Most studies using escalated doses of active agents in soft-tissue sarcomas followed by haematopoietic support measures have consistently demonstrated response rates of 40-50% compared with 20-30% following standard-dose chemotherapy. However, only a small proportion of complete remissions was achieved, and the overall duration of responses was not longer than for standard therapy. Currently dose-intensified chemotherapy cannot be regarded as standard treatment for soft-tissue sarcomas, and its value must be studied in controlled clinical trials. With the availability of new methods for haematopoietic support, such as myeloid growth factors and peripheral blood progenitor cells, the hypothesis of a dose-response relationship in soft-tissue sarcoma can be clinically tested. Its potential implication for cure should be further studied in a neoadjuvant or adjuvant setting.

Keywords:
Soft-tissue sarcoma, Drug therapy, Dose intensification, Haematopoietic growth factors, Peripheral blood stem cells, Biological response modifiers
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© 1994 S. Karger AG, Basel
1994
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