在乳腺癌和卵巢癌患者中给予紫杉醇、环磷酰胺和非格司亭后采集外周血干细胞。
Collection of peripheral blood stem cells following administration of paclitaxel, cyclophosphamide, and filgrastim in patients with breast and ovarian cancer.
作者信息
Weaver C H, Schwartzberg L S, Birch R, Greco F A, Hainsworth J, Drapkin R, Campos L, Grapski R, Schwerkoske J, Lautersztain J, Hazelton B, Schnell F, Babcock W, Buckner C D
机构信息
Clinical Research Division of Response Oncology, Inc., Memphis, TN, USA.
出版信息
Biol Blood Marrow Transplant. 1997 Jun;3(2):83-90.
PURPOSE
To determine the toxicities and efficacy of paclitaxel, cyclophosphamide (Cy), and recombinant human granulocyte-colony stimulating factor (filgrastim) administered for mobilization and collection of peripheral blood stem cells (PBSC) in patients with breast and ovarian cancer.
METHODS
One hundred and forty-one patients with breast (n = 115) or ovarian cancer (n = 26) received paclitaxel 170 mg/m2 and Cy 2 gm/m2 (n = 42) or paclitaxel 200 mg/m2, Cy 3 gm/m2 (n = 99), and filgrastim (6 micrograms/kg/day) followed by collection of PBSC by apheresis.
RESULTS
The 2 dose levels of paclitaxel and Cy tested were well tolerated. The median yield of CD34+ cells from all patients was 6.53 x 10(6)/kg (range, 0.11-51.76) collected with a median of 2 aphereses (range, 1-8). The target dose of 2.5 x 10(6) CD34+ cells/kg was achieved in 85% of patients. The mean daily collection of CD34+ cells was 5.46 x 10(6)/kg for patients receiving 200 mg/m2 of paclitaxel and 3 gm/m2 of Cy as compared to 2.77 for patients receiving the lower doses (p = 0.0005). Increasing the dose of paclitaxel and Cy did not significantly increase the fraction of patients achieving a target dose of 2.5 x 10(6) CD34+ cells/kg (87% vs 81%, p = 0.367) but did increase the fraction achieving a target of 5.0 x 10(6) CD34+ cells/kg (73% vs 45%, p = 0.002). The mean daily collection of CD34+ cells for patients who had received only 1 prior chemotherapy regimen was 6.59 x 10(6)/kg as compared to 3.47 for patients who had received more than 1 prior chemotherapy regimen (p < 0.0001). Prior radiation therapy (p = 0.003) and patient performance status (p = 0.047) were adverse risk factors for achieving a target dose of > or = 2.5 x 10(6) CD34+ cells/kg.
CONCLUSIONS
The combination of paclitaxel, Cy, and filgrastim can be administered with acceptable toxicity, allowing collection of adequate quantities of PBSC from the majority of patients with breast and ovarian cancer. Increasing the doses of paclitaxel and Cy increased the number of CD34+ cells collected and decreased the number of apheresis procedures necessary to collect target cell doses. However, increasing drug doses did not increase the fraction of patients yielding the minimum CD34+ target dose of 2.5 x 10(6)/kg. Collection of PBSC early in the disease course is the best strategy to assure optimal CD34+ cell doses in all patients.
目的
确定紫杉醇、环磷酰胺（Cy）和重组人粒细胞集落刺激因子（非格司亭）用于动员和采集乳腺癌及卵巢癌患者外周血干细胞（PBSC）的毒性和疗效。
方法
141例乳腺癌患者（n = 115）或卵巢癌患者（n = 26）接受紫杉醇170 mg/m²和Cy 2 g/m²（n = 42）或紫杉醇200 mg/m²、Cy 3 g/m²（n = 99），以及非格司亭（6微克/千克/天），随后通过单采术采集PBSC。
结果
所测试的2个紫杉醇和Cy剂量水平耐受性良好。所有患者CD34⁺细胞的中位采集量为6.53×10⁶/kg（范围为0.11 - 51.76），中位采集次数为2次（范围为1 - 8次）。85%的患者达到了2.5×10⁶个CD34⁺细胞/kg的目标剂量。接受200 mg/m²紫杉醇和3 g/m² Cy的患者CD34⁺细胞的日均采集量为5.46×10⁶/kg，而接受较低剂量的患者为2.77×10⁶/kg（p = 0.0005）。增加紫杉醇和Cy的剂量并未显著提高达到2.5×10⁶个CD34⁺细胞/kg目标剂量的患者比例（87%对81%，p = 0.367），但确实提高了达到5.0×10⁶个CD34⁺细胞/kg目标的患者比例（73%对45%，p = 0.002）。仅接受过1次既往化疗方案的患者CD34⁺细胞的日均采集量为6.59×10⁶/kg，而接受过1次以上既往化疗方案的患者为3.47×10⁶/kg（p < 0.0001）。既往放疗（p = 0.003）和患者的体能状态（p = 0.047）是达到≥2.5×10⁶个CD34⁺细胞/kg目标剂量的不良风险因素。
结论
紫杉醇、Cy和非格司亭联合应用的毒性可接受，能使大多数乳腺癌和卵巢癌患者采集到足够数量的PBSC。增加紫杉醇和Cy的剂量可增加CD34⁺细胞的采集数量，并减少采集目标细胞剂量所需的单采术次数。然而，增加药物剂量并未提高产生最低CD34⁺目标剂量2.5×10⁶/kg的患者比例。在疾病进程早期采集PBSC是确保所有患者获得最佳CD34⁺细胞剂量的最佳策略。
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