Giaccone Giuseppe, Debruyne Channa, Felip Enriqueta, Chapman Paul B, Grant Stefan C, Millward Michael, Thiberville Luc, D'addario Giannicola, Coens Corneel, Rome Lisa S, Zatloukal Petr, Masso Oriol, Legrand Catherine
Division of Medical Oncology, Vrije Universiteit Medical Center, 1117 De Boelelaan, Amsterdam, the Netherlands.
J Clin Oncol. 2005 Oct 1;23(28):6854-64. doi: 10.1200/JCO.2005.17.186.
Bec2 is an anti-idiotypic antibody that mimics GD3, a ganglioside that is expressed on the surface of tumor cells and is of neuroectodermal origin. We assessed whether Bec2/bacille Calmette-Guerin (BCG) vaccination prolongs survival in patients with limited-disease small-cell lung cancer (SCLC) after a major response to chemotherapy and chest radiation.
Patients were randomly assigned to receive five vaccinations of Bec2 (2.5 mg)/BCG vaccine or follow-up. Vaccination was given over a 10-week period. The sample size was targeted to detect an increase in median survival of 40% after random assignment, and stratification was by performance status, response, and institution. Quality of life was assessed by using the European Organisation for Research and Treatment of Cancer instrument. Humoral response was assessed in patients who received vaccination.
A total of 515 patients were randomly assigned. The primary toxicities of vaccination were transient skin ulcerations and mild flu-like symptoms. There was no improvement in survival, progression-free survival, or quality of life in the vaccination arm. Median survival from randomization was 16.4 and 14.3 months in the observation and vaccination arms (P = .28), respectively. Among vaccinated patients, a trend toward prolonged survival was observed in those (one third) who developed a humoral response (P = .085). Multivariate analysis showed a positive impact on survival by prior treatment with concomitant chemoradiotherapy, prophylactic cranial irradiation, female sex, low lactate dehydrogenase, and normal platelets.
Vaccination with Bec2/BCG has no impact on outcome of patients with limited-disease SCLC responding to combined-modality treatment. Vaccination strategies in SCLC may still be warranted using vaccines that produce a better immunologic response.
Bec2是一种抗独特型抗体，可模拟GD3（一种在肿瘤细胞表面表达且起源于神经外胚层的神经节苷脂）。我们评估了Bec2/卡介苗（BCG）疫苗接种能否延长对化疗和胸部放疗有显著反应的局限性小细胞肺癌（SCLC）患者的生存期。
患者被随机分配接受5次Bec2（2.5毫克）/BCG疫苗接种或随访。接种在10周内完成。样本量旨在检测随机分组后中位生存期增加40%，并按体能状态、反应和机构进行分层。使用欧洲癌症研究与治疗组织的工具评估生活质量。对接种疫苗的患者评估体液反应。
共515例患者被随机分配。疫苗接种的主要毒性为短暂性皮肤溃疡和轻度流感样症状。接种组在生存期、无进展生存期或生活质量方面均无改善。随机分组后的中位生存期在观察组和接种组分别为16.4个月和14.3个月（P = 0.28）。在接种疫苗的患者中，出现体液反应的患者（三分之一）有生存期延长的趋势（P = 0.085）。多因素分析显示，先前接受同步放化疗、预防性颅脑照射、女性、低乳酸脱氢酶和正常血小板对生存期有积极影响。
Bec2/BCG疫苗接种对接受综合治疗的局限性SCLC患者的预后无影响。使用能产生更好免疫反应的疫苗，SCLC的疫苗接种策略可能仍有必要。
