Sutton G P, Blessing J A, Rosenshein N, Photopulos G, DiSaia P J
Department of Obstetrics and Gynecology, Indiana University Medical School, Indianapolis 46223.
Am J Obstet Gynecol. 1989 Aug;161(2):309-12. doi: 10.1016/0002-9378(89)90507-3.
A phase II trial of ifosfamide (isophosphamide, NSC 109724) and mesna (2-mercaptoethane sodium sulfonate, NSC 113891) in women with advanced or recurrent mixed mullerian tumors of the uterus was conducted by the Gynecologic Oncology Group. The starting dose of ifosfamide was 1.5 gm/m2 daily, intravenously, for 5 days. The starting dose of ifosfamide was reduced 1.2 gm/m2 daily in patients who had received prior radiotherapy. Mesna was given intravenously immediately and at 4 and 8 hours after the administration of ifosfamide. Each mesna dose was 20% of the total daily dose of ifosfamide. Twenty-nine patients are evaluable for toxicity, and 28 patients are evaluable for response. Twenty-one patients had received prior abdominal hysterectomy, and eight patients had prior radiotherapy. Thirteen tumors were homologous and 15 heterologous. Gynecologic Oncology Group grade 3 or 4 granulocytopenia occurred in seven (25%) patients and two (7.1%) had grade 3 or 4 thrombocytopenia. Two patients (7.1%) had grade 3 or 4 neurotoxicity. One patient experienced lethargy and confusion that responded to discontinuation of the ifosfamide. A second patient developed progressive cerebellar dysfunction, left hemiparesis, and coma. This patient died after 3 days of therapy. Complete responses were seen in five (17.9%) patients and partial responses occurred in four (14.3%) patients for a total response rate of 32.2%. These results indicate that ifosfamide is an unusually active drug in patients with advanced or recurrent mixed mullerian tumors of the uterus. Studies with combination regimens incorporating ifosfamide are warranted. The toxicity of ifosfamide in Gynecologic Oncology Group studies is being evaluated retrospectively.
妇科肿瘤研究组对异环磷酰胺（异磷酰胺，NSC 109724）和美司钠（2-巯基乙烷磺酸钠，NSC 113891）用于晚期或复发性子宫混合性苗勒管肿瘤女性患者进行了一项II期试验。异环磷酰胺的起始剂量为每日1.5 g/m²，静脉给药，共5天。对于之前接受过放疗的患者，异环磷酰胺的起始剂量减至每日1.2 g/m²。美司钠在异环磷酰胺给药后即刻、4小时和8小时静脉给药。美司钠的每次剂量为异环磷酰胺每日总剂量的20%。29例患者可评估毒性，28例患者可评估疗效。21例患者之前接受过腹式子宫切除术，8例患者之前接受过放疗。13例肿瘤为同源性，15例为异源性。7例（25%）患者发生了妇科肿瘤研究组3级或4级粒细胞减少，2例（7.1%）发生了3级或4级血小板减少。2例患者（7.1%）发生了3级或4级神经毒性。1例患者出现嗜睡和意识模糊，停用异环磷酰胺后症状缓解。另1例患者出现进行性小脑功能障碍、左侧偏瘫和昏迷。该患者在治疗3天后死亡。5例（17.9%）患者出现完全缓解，4例（14.3%）患者出现部分缓解，总缓解率为32.2%。这些结果表明，异环磷酰胺在晚期或复发性子宫混合性苗勒管肿瘤患者中是一种活性异常高的药物。有必要开展含异环磷酰胺联合方案的研究。正在对妇科肿瘤研究组研究中异环磷酰胺的毒性进行回顾性评估。
