Doxorubicin (or epidoxorubicin) combined with ifosfamide in the treatment of adult advanced soft tissue sarcomas

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Abstract
The results of the association of doxorubicin plus ifosfamide in the treatment of locally advanced and/or metastatic adult soft tissue sarcomas as reported in the literature from 1986 up to the present time are reviewed. The data confirm the effectiveness of the association doxorubicin plus ifosfamide, with an objective response rate of 33.25% (range, 22% to 42%), with 9.3% of complete responses. The highest percentages were reported in studies using doses of doxorubicin of 60 mg/m2 or higher, with a suggested dose-response correlation. The pattern is generally well tolerated, with a prevalently haematological toxicity. Results being equal, the use of epidoxorubicin seems to allow a lower incidence of high grade leukopenia, and an higher dose-intensity of the drug administered. The two randomized studies by EORTC and ECOG indicate superiority of this combination compared to doxorubicin on its own or with other polychemotherapeutic regimens containing doxorubicin, without ifosfamide. However, the actual contribution of ifosfamide deserves further investigation. The impact on long-term disease-free survival is, however, poor and median survival time ranges from 8 to 12 months in responder patients. Future studies should be aimed at increasing the dosages of the drugs without a significant increase of toxicity, by administering them in continuous infusion or by the use of growth factors.