Frustaci S, De Paoli A, Bidoli E, La Mura N, Berretta M, Buonadonna A, Boz G, Gherlinzoni F
Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano, General Hospital, Gorizia, Italy.
Oncology. 2003;65 Suppl 2:80-4. doi: 10.1159/000073366.
Ifosfamide and anthracyclines are the only active agents in advanced soft tissue sarcomas. Doxorubicin was always used in sarcomas, whereas ifosfamide was reintroduced in the clinic after the discovery of mesna which prevents its typical dose-limiting toxicity: hemorrhagic cystitis. In the adjuvant setting, doxorubicin was used alone or in combination in the first-generation trials, whereas its parent compounds epirubicin and ifosfamide were employed in the second-generation adjuvant trials, which started in the early 90s. Other relevant aspects of the second-generation trials are the use of the hematopoietic growth factors and the increase of the dose intensity, the introduction of more restrictive selection criteria and the use of the two most active agents, ifosfamide and anthracyclines. Only the Italian cooperative trial has been concluded, and the results reported and updated. After a median follow-up of 89.6 months (range 56-119), the intention-to-treat analysis still reveals a difference in overall survival which, however, is not statistically significant. However, the 5-year overall survival estimate, which is a reasonable end point for the survival analysis of adjuvant treatment in soft tissue sarcomas, was 66.0 and 46.1% for the treatment and the control groups, respectively (p = 0.04).
异环磷酰胺和蒽环类药物是晚期软组织肉瘤仅有的有效药物。多柔比星一直用于肉瘤治疗，而异环磷酰胺在发现美司钠（可预防其典型的剂量限制性毒性：出血性膀胱炎）后重新应用于临床。在辅助治疗方面，第一代试验单独或联合使用多柔比星，而第二代辅助试验始于20世纪90年代初，使用其母体化合物表柔比星和异环磷酰胺。第二代试验的其他相关方面包括造血生长因子的使用和剂量强度的增加、引入更严格的选择标准以及使用两种最有效的药物——异环磷酰胺和蒽环类药物。只有意大利的合作试验已经结束，并报告和更新了结果。中位随访89.6个月（范围56 - 119个月）后，意向性分析仍显示总生存存在差异，但无统计学意义。然而，5年总生存估计值（这是软组织肉瘤辅助治疗生存分析的一个合理终点）在治疗组和对照组分别为66.0%和46.1%（p = 0.04）。
