Aglietta M, Montemurro F, Fagioli F, Volta C, Botto B, Cantonetti M, Racanelli V, Teofili L, Ferrara R, Amadori S, Castoldi G L, Dammacco F, Levis A
Divisione Universitaria di Oncologia ed Ematologia, Ospedale Mauriziano Umberto I-Istituto per la Ricerca e la Cura del Cancro (I. R.C.C.), Torino, Italy.
Cancer. 2000 Jan 15;88(2):454-60. doi: 10.1002/(sici)1097-0142(20000115)88:2<454::aid-cncr28>3.0.co;2-q.
Granulocyte-macrophage-colony stimulating factor (GM-CSF) administration stimulates the proliferation of hemopoietic progenitors. Shortly (48-96 hours) after its discontinuation, feedback phenomena occur and the progenitor proliferation rate drops below baseline levels. As the quiescence of hyperplastic bone marrow suggests that hemopoietic cells may be refractory to the toxic effects of cytostatic drugs, the decision was made to test the hypothesis that GM-CSF given before chemotherapy may be myeloprotective.
Fifty-six patients with newly diagnosed Stage II-IV Hodgkin disease, ages 18-77 years, were randomized to receive GM-CSF (5 microg/kg subcutaneously) or placebo from Day 7 to Day 4 before each chemotherapy administration (6 cycles of a hybrid of mechlorethamine, vincristine, procarbazine, and prednisone with doxorubicin, bleomycin, vinblastine, and dacarbazine). The treatment was considered a success if the delivery rate of chemotherapy was >90% after 3 cycles and >80% after 6 cycles.
Thirty patients received GM-CSF and 26 placebo. The dose intensity (85.2% vs. 79.6%) and the overall success in terms of delivery rate (56.7% vs. 50%) were higher in the GM-CSF group, although these differences were not statistically significant. The neutrophil nadirs were higher in the GM-CSF group during the first three cycles and subsequently similar in both groups.
No significant differences in terms of myelotoxicity or drug delivery were observed between the two treatment arms. Although the myeloprotective effect of the prechemotherapy administration of GM-CSF seems to be minimal, the data indicate a safe timing between GM-CSF discontinuation and further chemotherapy. Because cumulative myelotoxicity has been observed with other growth factors, given in the interval between the chemotherapy cycles, this may be relevant to the planning of rapid cycling.
给予粒细胞巨噬细胞集落刺激因子（GM-CSF）可刺激造血祖细胞增殖。在停药后不久（48 - 96小时），会出现反馈现象，祖细胞增殖率降至基线水平以下。鉴于增生性骨髓的静止状态提示造血细胞可能对细胞毒性药物的毒性作用具有抗性，因此决定检验化疗前给予GM-CSF可能具有骨髓保护作用这一假设。
56例新诊断为II - IV期霍奇金病的患者，年龄在18 - 77岁之间，在每次化疗给药前7天至第4天（采用氮芥、长春新碱、丙卡巴肼和泼尼松与多柔比星、博来霉素、长春碱和达卡巴嗪联合的6个周期化疗方案）被随机分为接受GM-CSF（5微克/千克皮下注射）或安慰剂组。如果3个周期后化疗给药率>90%且6个周期后>80%，则该治疗被视为成功。
30例患者接受GM-CSF，26例接受安慰剂。GM-CSF组的剂量强度（85.2%对79.6%）和给药率方面的总体成功率（56.7%对50%）更高，尽管这些差异无统计学意义。GM-CSF组在前三个周期中性粒细胞最低点较高，随后两组相似。
在两个治疗组之间未观察到骨髓毒性或药物给药方面的显著差异。尽管化疗前给予GM-CSF的骨髓保护作用似乎很小，但数据表明GM-CSF停药与进一步化疗之间的安全时间间隔。由于在化疗周期之间给予其他生长因子时已观察到累积骨髓毒性，这可能与快速循环的计划相关。
