Yeung A W, Pang Y K, Tsang Y C, Wong S W
Oncology Unit, Hong Kong Sanatorium and Hospital.
Cancer. 1994 Apr 1;73(7):1960-70. doi: 10.1002/1097-0142(19940401)73:7<1960::aid-cncr2820730730>3.0.co;2-h.
High-dose chemotherapy with autologous bone marrow transplantation has been useful in some patients with advanced breast, lymphoma, or germ cell tumors. Double-cycle high-dose chemotherapy may be able to deliver an even higher total dose within a given time period. It is important to determine whether peripheral blood stem cells and hematopoietic growth factors can diminish the hematopoietic toxicity of such a treatment.
From November 1989 to May 1991, 14 patients were enrolled in two cycles of high-dose chemotherapy consisting of cyclophosphamide, 4.5 g/m2; cisplatin, 150 mg/m2; and etoposide, 900 mg/m2 in each cycle. The first five patients received peripheral blood stem cells harvested from 8-10 leukaphereses during steady state. The next nine patients, besides receiving peripheral blood stem cells mobilized by growth factors, also received either granulocyte-macrophage colony-stimulating factor (GM-CSF) at 250 micrograms/m2/day by two subcutaneous (s.c.) injections given 12 hours apart from day 6 until neutrophil recovery or granulocyte colony-stimulating factor (G-CSF) at 200 micrograms/m2 as daily s.c. injections.
For the first five patients, there was a median of 14 days from the first day of absolute marrow suppression to neutrophil count exceeding 500/microliters and a median of 15 days for a platelet count exceeding 20,000/microliters. For the next nine patients, with the use of either G-CSF or GM-CSF, there was a median of 8 days for a neutrophil count exceeding 500/microliters and and a median of 11 days for a platelet count exceeding 20,000/microliters.
With the use of peripheral stem cells and growth factors, high-dose chemotherapy could be given safely every 30 days with acceptable toxicity. A high complete response rate was seen in patients with nasopharyngeal carcinoma and in patients with small cell and non-small cell lung cancer who either had not received previous chemotherapy or who had responded to previous chemotherapy.
大剂量化疗联合自体骨髓移植对一些晚期乳腺癌、淋巴瘤或生殖细胞肿瘤患者有效。双周期大剂量化疗或许能够在给定时间内给予更高的总剂量。确定外周血干细胞和造血生长因子能否减轻此类治疗的造血毒性很重要。
1989年11月至1991年5月，14例患者接受了两个周期的大剂量化疗，每个周期包括环磷酰胺4.5 g/m²、顺铂150 mg/m²和依托泊苷900 mg/m²。前5例患者接受了在稳定状态下通过8 - 10次白细胞分离术采集的外周血干细胞。接下来的9例患者，除了接受生长因子动员的外周血干细胞外，还在第6天至中性粒细胞恢复期间，每隔12小时皮下注射250微克/m²/天的粒细胞-巨噬细胞集落刺激因子（GM-CSF），或每天皮下注射200微克/m²的粒细胞集落刺激因子（G-CSF）。
对于前5例患者，从绝对骨髓抑制的第一天到中性粒细胞计数超过500/微升的中位时间为14天，血小板计数超过20,000/微升的中位时间为15天。对于接下来的9例患者，使用G-CSF或GM-CSF后，中性粒细胞计数超过500/微升的中位时间为8天，血小板计数超过20,000/微升的中位时间为11天。
使用外周干细胞和生长因子后，每30天安全给予大剂量化疗，毒性可接受。在鼻咽癌患者以及未接受过先前化疗或对先前化疗有反应的小细胞和非小细胞肺癌患者中观察到了较高的完全缓解率。
