Demirer T, Ilhan O, Mandel N M, Arat M, Günel N, Celebi H, Ustün C, Akan H, Demirer S, Aydintuğ S, Uysal A, Koç H
Ankara University Medical School, Ibni Sina Hospital, Department of Hematology/Oncology and Bone Marrow Transplant Unit, Ankara, Turkey.
Bone Marrow Transplant. 2000 Apr;25(7):697-703. doi: 10.1038/sj.bmt.1702239.
The purpose of this study was to determine the maximum tolerated dose of carboplatin administered with 500 mg/m2 thiotepa and 100 mg/m2 melphalan followed by autologous peripheral blood stem cell (PBSC) infusion in patients with refractory malignancies. Twenty-eight patients with refractory malignancies received high-dose thiotepa (500 mg/m2, melphalan (100 mg/m2) and escalating doses of carboplatin 900-1500 mg/m2) followed by infusion of cryopreserved autologous PBSCs. The maximum tolerated doses were determined to be 500 mg/m2 thiotepa, 100 mg/m2 melphalan and 1350 mg/m2 carboplatin. Two consecutive patients receiving 1500 mg/m2 carboplatin experienced grade 3 mucositis and colitis. Ten patients were enrolled at the maximum tolerated dose and none had grade 3-4 regimen-related toxicity and mortality. All patients at this level experienced grade 1-2 mucositis, 90% grade 1-2 gastrointestinal toxicity, 30% grade 1-2 cardiac and renal toxicity, and 10% experienced grade 1 hepatic toxicity. The median time to achieve a granulocyte count of 0.5x10(9)/l was 9 days (range 7-12 days) and platelet count of 20x10(9)/l was 10 days (range 7-15 days). Of eight patients with stage IV refractory breast cancer, even were evaluable for response, one patient on day 75 will be evaluated soon. Five of seven (71.5%) evaluable patients achieved a complete remission (CR) and two had no response. Of seven patients with non-Hodgkin's lymphoma (n = 4) or Hodgkin's disease (n = 3), five achieved a CR (71.5%). Thiotepa, melphalan and carboplatin can be administered in high doses with tolerable mucositis as the major side-effect. This combination has significant activity in patients with breast cancer, and phase II studies in patients with breast cancer and other chemotherapy-sensitive malignancies are warranted.
本研究的目的是确定在难治性恶性肿瘤患者中，与500mg/m²的噻替派和100mg/m²的美法仑联合使用时卡铂的最大耐受剂量，随后进行自体外周血干细胞（PBSC）输注。28例难治性恶性肿瘤患者接受了高剂量的噻替派（500mg/m²）、美法仑（100mg/m²）以及递增剂量的卡铂（900 - 1500mg/m²），随后输注冷冻保存的自体PBSC。确定的最大耐受剂量为500mg/m²的噻替派、100mg/m²的美法仑和1350mg/m²的卡铂。连续两名接受1500mg/m²卡铂的患者出现3级粘膜炎和结肠炎。10例患者按最大耐受剂量入组，无一例出现3 - 4级与治疗方案相关的毒性反应和死亡。在此剂量水平下，所有患者均出现1 - 2级粘膜炎，90%出现1 - 2级胃肠道毒性，30%出现1 - 2级心脏和肾脏毒性，10%出现1级肝脏毒性。达到粒细胞计数0.5×10⁹/L的中位时间为9天（范围7 - 12天），血小板计数20×10⁹/L的中位时间为10天（范围7 - 15天）。在8例IV期难治性乳腺癌患者中，7例可评估疗效，1例患者在第75天即将接受评估。7例可评估疗效的患者中，5例（71.5%）达到完全缓解（CR），2例无反应。在7例非霍奇金淋巴瘤（n = 4）或霍奇金病（n = 3）患者中，5例达到CR（71.5%）。噻替派、美法仑和卡铂可以高剂量给药，主要副作用为可耐受的粘膜炎。这种联合方案在乳腺癌患者中具有显著活性，有必要对乳腺癌和其他化疗敏感的恶性肿瘤患者进行II期研究。
