Lucidarme N, Valteau-Couanet D, Oberlin O, Couanet D, Kalifa C, Beaujean F, Lapierre V, Hartmann O
Pediatrics Department, Institut Gustave Roussy, Villejuif, France.
Bone Marrow Transplant. 1998 Sep;22(6):535-40. doi: 10.1038/sj.bmt.1701395.
From 1987 to 1995, 22 children with refractory solid tumors entered a phase II study of high-dose thiotepa (HDT) (900 mg/m2) followed by stem cell transplantation (SCT) in the Pediatrics Department of the Institut Gustave Roussy. Tumor types were rhabdomyosarcoma (eight), osteosarcoma (seven), neuroblastoma (three), Ewing's sarcoma (three) and Burkitt's lymphoma (one). Before HDT, all had been extensively treated with conventional chemotherapy, surgical resection of the primary tumor (13/22) and of metastases (6/22), and radiotherapy of the primary tumor in three patients. All had measurable disease, at the site of the primary tumor (3 patients), of the metastases (9 patients) or both (10 patients). Toxicity from the HDT was severe but acceptable. No toxicity-related death occurred. The median duration of neutropenia and thrombocytopenia was 18 days (5-37) and 30 days (7-377), respectively. Septicemia was documented in four patients. Severe diarrhea was observed in seven patients. Mild hepatic toxicity occurred 18 times. No CR and 11/22 PR were documented: osteosarcoma 4/7, rhabdomyosarcoma 4/8, Ewing's sarcoma 2/3; 1/1 Burkitt's lymphoma progressed. We conclude that at a dose of 900 mg/m2 followed by SCT support in these heavily pretreated children, the main toxicity induced by thiotepa was digestive. The response rate observed, especially in sarcoma, is particularly encouraging. Thiotepa should be further evaluated in HDC regimens either in combination with other alkylating agents or in rapidly cycled courses of HDC with SCT.
1987年至1995年，22例患有难治性实体瘤的儿童进入了古斯塔夫·鲁西研究所儿科的一项II期研究，接受大剂量噻替派（HDT）（900 mg/m²）治疗，随后进行干细胞移植（SCT）。肿瘤类型包括横纹肌肉瘤（8例）、骨肉瘤（7例）、神经母细胞瘤（3例）、尤因肉瘤（3例）和伯基特淋巴瘤（1例）。在进行HDT之前，所有患儿均已接受过广泛的传统化疗、原发性肿瘤（13/22）和转移灶（6/22）的手术切除，3例患儿还接受了原发性肿瘤的放射治疗。所有患儿均有可测量的疾病，位于原发性肿瘤部位（3例）、转移灶部位（9例）或两者皆有（10例）。HDT的毒性严重但可接受。未发生与毒性相关的死亡。中性粒细胞减少和血小板减少的中位持续时间分别为18天（5 - 37天）和30天（7 - 377天）。4例患儿记录有败血症。7例患儿观察到严重腹泻。轻度肝毒性发生18次。未记录到完全缓解（CR），11/22例部分缓解（PR）：骨肉瘤4/7、横纹肌肉瘤4/8、尤因肉瘤2/3；1/1例伯基特淋巴瘤病情进展。我们得出结论，在这些经过大量预处理的儿童中，给予900 mg/m²剂量的噻替派并辅以SCT支持，噻替派诱导的主要毒性是消化系统毒性。观察到的缓解率，尤其是在肉瘤患者中，特别令人鼓舞。噻替派应在大剂量化疗（HDC）方案中进一步评估，可与其他烷化剂联合使用，或在快速循环的HDC联合SCT疗程中使用。
