Bunn P A, Crowley J, Kelly K, Hazuka M B, Beasley K, Upchurch C, Livingston R, Weiss G R, Hicks W J, Gandara D R
Division of Medical Oncology, University of Colorado, Denver, USA.
J Clin Oncol. 1995 Jul;13(7):1632-41. doi: 10.1200/JCO.1995.13.7.1632.
This phase III randomized trial was designed to determine if granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the hematologic toxicity and morbidity induced by chemoradiotherapy in limited-stage small-cell lung cancer (SCLC).
This multicenter prospective trial randomized 230 patients to receive chemotherapy and radiotherapy (RT) with or without GM-CSF given on days 4 to 18 of each of six cycles. The primary end point was hematologic toxicity. Secondary end points included the following: nonhematologic toxicities; days of (1) fever, (2) antibiotics, (3) hospitalization, and (4) infection; number of transfusions; drug doses delivered; and response rates and survival.
There was a statistically significant increase in the frequency and duration of life-threatening thrombocytopenia (P < .001) in patients randomized to GM-CSF. GM-CSF patients had significantly more toxic deaths (P < .01), more nonhematologic toxicities, more days in hospital, a higher incidence of intravenous (IV) antibiotic usage, and more transfusions. Patients randomized to GM-CSF had higher WBC and neutrophil nadirs (P < .01), but no significant difference in the frequency of grade 4 leukopenia or neutropenia. Patients randomized to GM-CSF had a lower complete response rate (36% v 44%), but the differences were not significant (P = .29). There were no significant differences in survival (median, 14 months on GM-CSF and 17 months on no GM-CSF; P = .15).
GM-CSF, as delivered in this study, should not be included with concurrent chemoradiotherapy treatment programs for limited-stage SCLC. The simultaneous use of hematopoietic colony-stimulating factors (CSFs) and chemoradiotherapy should be performed only in experimental settings. Chemoradiotherapy programs with cisplatin and etoposide ([VP-16] PE) and simultaneous chest RT produce grade 4 neutropenia and thrombocytopenia in a small-enough proportion of patients that prophylactic hematopoietic growth factors are clinically unnecessary.
本III期随机试验旨在确定粒细胞-巨噬细胞集落刺激因子（GM-CSF）是否能降低局限期小细胞肺癌（SCLC）放化疗所致的血液学毒性和发病率。
这项多中心前瞻性试验将230例患者随机分为两组，在六个周期的每个周期的第4至18天接受化疗和放疗（RT），一组加用GM-CSF，另一组不加。主要终点是血液学毒性。次要终点包括：非血液学毒性；（1）发热、（2）使用抗生素、（3）住院和（4）感染的天数；输血次数；给予的药物剂量；缓解率和生存率。
随机接受GM-CSF治疗的患者中，危及生命的血小板减少症的频率和持续时间有统计学显著增加（P <.001）。接受GM-CSF治疗的患者有更多的毒性死亡（P <.01）、更多的非血液学毒性、更长的住院天数、更高的静脉用抗生素使用率和更多的输血。随机接受GM-CSF治疗的患者白细胞和中性粒细胞最低点更高（P <.01），但4级白细胞减少或中性粒细胞减少的频率无显著差异。随机接受GM-CSF治疗的患者完全缓解率较低（36%对44%），但差异不显著（P =.29）。生存率无显著差异（GM-CSF组中位生存期为14个月，未用GM-CSF组为17个月；P =.15）。
本研究中使用的GM-CSF不应纳入局限期SCLC的同步放化疗治疗方案。造血集落刺激因子（CSF）与放化疗同时使用应仅在实验环境中进行。顺铂和依托泊苷（[VP-16]PE）联合同步胸部放疗的放化疗方案在足够少比例的患者中会产生4级中性粒细胞减少和血小板减少，因此临床上无需预防性使用造血生长因子。
