Edmonson J H, Ryan L M, Blum R H, Brooks J S, Shiraki M, Frytak S, Parkinson D R
Mayo Clinic, Rochester, MN 55905.
J Clin Oncol. 1993 Jul;11(7):1269-75. doi: 10.1200/JCO.1993.11.7.1269.
This three-armed phase III study in adults with advanced soft tissue sarcomas was planned as a comparison of objective regression rates, toxicity, and survival of patients receiving doxorubicin alone, ifosfamide plus doxorubicin, and mitomycin plus doxorubicin plus cisplatin.
Between December 1987 and July 1990, 279 patients with histologically confirmed sarcomas were enrolled to receive treatment A (doxorubicin 80 mg/m2), treatment B (ifosfamide 7.5 g/m2 plus doxorubicin 60 mg/m2), or treatment C (mitomycin 8 mg/m2 plus doxorubicin 40 mg/m2 plus cisplatin 60 mg/m2).
Of 262 assessable patients, 74 (29%) achieved objective tumor regression. Objective regression occurred in 20% of the 90 patients who received doxorubicin alone (complete remission [CR] rate, 2%), in 34% of the 88 who received ifosfamide plus doxorubicin (CR rate, 3%), and in 32% of the 84 who received mitomycin plus doxorubicin plus cisplatin (CR rate, 7%). With grade 3 or greater myelosuppression in 53% of group A, 80% of group B, and 55% of group C, regimen B was significantly more myelosuppressive than either regimen A or C (P = .01) with two, three, and one treatment-related deaths, respectively. Synovial sarcomas were responsive to ifosfamide plus doxorubicin, especially among patients younger than 40 years of age.
Ifosfamide plus doxorubicin produced a significantly higher regression rate (P = .03) than did doxorubicin alone; however, this was achieved at a level of myelosuppression significantly more intense than that produced by the single agent or by the three-drug combination. Mitomycin, doxorubicin, and cisplatin also appeared to be more active than the single agent; however, at a myelosuppression level similar to that of doxorubicin alone, this trend (P = .07) did not attain the usual level for significance. No significant survival differences were observed.
本三项臂的III期研究针对患有晚期软组织肉瘤的成人患者，旨在比较单独接受阿霉素、异环磷酰胺加阿霉素以及丝裂霉素加阿霉素加顺铂治疗的患者的客观缓解率、毒性和生存率。
在1987年12月至1990年7月期间，279例经组织学确诊为肉瘤的患者入组，接受治疗A（阿霉素80mg/m²）、治疗B（异环磷酰胺7.5g/m²加阿霉素60mg/m²）或治疗C（丝裂霉素8mg/m²加阿霉素40mg/m²加顺铂60mg/m²）。
在262例可评估患者中，74例（29%）实现了客观肿瘤缓解。单独接受阿霉素治疗的90例患者中，20%出现客观缓解（完全缓解[CR]率为2%）；接受异环磷酰胺加阿霉素治疗的88例患者中，34%出现客观缓解（CR率为3%）；接受丝裂霉素加阿霉素加顺铂治疗的84例患者中，32%出现客观缓解（CR率为7%）。A组53%、B组80%和C组55%的患者出现3级或更高级别的骨髓抑制，方案B的骨髓抑制作用明显强于方案A或C（P = 0.01），分别有2例、3例和1例与治疗相关的死亡。滑膜肉瘤对异环磷酰胺加阿霉素有反应，尤其是在40岁以下的患者中。
异环磷酰胺加阿霉素产生的缓解率（P = 0.03）明显高于单独使用阿霉素；然而，这是在骨髓抑制程度明显高于单药或三药联合方案的情况下实现的。丝裂霉素、阿霉素和顺铂似乎也比单药更有效；然而，在与单独使用阿霉素相似的骨髓抑制水平下，这种趋势（P = 0.07）未达到通常的显著性水平。未观察到显著的生存差异。
