Lasalvia-Prisco Eduardo, Garcia-Giralt Emilio, Vázquez Jesús, Aghazarian Marta, Lasalvia-Galante Eduardo, Larrañaga Joshemaria, Spera Gonzalo
Interdoctors Medical Procedures, North Miami Beach, FL, USA;
Biologics. 2008 Sep;2(3):555-61. doi: 10.2147/btt.s2685.
The purpose of this study was to compare chemotherapy-naive patients with stage IV nonsmall cell lung cancer patients treated with chemotherapy or chemoimmunotherapy. We tested doxetacel plus cisplatinum as chemotherapy protocol. An immunomodulatory adjuvant system was added as chemoimmunotherapy to the previously mentioned protocol. This system contains three well-known and complementary conditioners of protective immune-responses: cyclophosphamide low-dose, granulocyte macrophage-colony stimulant factor and magnesium silicate granuloma. Eighty-eight patients were randomly assigned to receive every 3-weeks one of the treatments under comparison. Patients received four cycles of treatment unless disease progression or unacceptable toxicity was documented. The maximum follow-up was one year. In each arm, tumor response (rate,duration), median survival time, 1-year overall survival, safety, and immunity modifications were assessed. Immunity was evaluated by submitting peripheral blood mononuclear cells to laboratory tests for nonspecific immunity: a) phytohemaglutinin-induced lymphocyte proliferation, b) prevalence of T-Regulatory (CD4+CD25+) cells and for specific immunity: a) lymphocyte proliferation induced by tumor-associated antigens (TAA) contained in a previously described autologous thermostable hemoderivative. The difference (chemotherapy vs. chemoimmunotherapy) in response rate induced by the two treatments (39.0% and 35.0%) was not statistically significant. However, the response duration (22 and 31 weeks), the median survival time (32 and 44 weeks) and 1-year survival (33.3% and 39.1%) were statistically higher with chemoimmunotherapy. No difference in toxicity between both arms was demonstrated. A switch in the laboratory immunity profile, nonspecific and specific, was associated with the chemoimmunotherapy treatment: increase of proliferative lymphocyte response, decrease of tolerogenic T-regulatory cells and eliciting TAA-sensitization.
本研究的目的是比较未经化疗的IV期非小细胞肺癌患者与接受化疗或化疗免疫疗法治疗的患者。我们测试了多西他赛加顺铂作为化疗方案。将一种免疫调节佐剂系统作为化疗免疫疗法添加到上述方案中。该系统包含三种著名且互补的保护性免疫反应调节剂：低剂量环磷酰胺、粒细胞巨噬细胞集落刺激因子和硅酸镁肉芽肿。88名患者被随机分配，每3周接受一种对比治疗。除非记录到疾病进展或出现不可接受的毒性，患者接受四个周期的治疗。最大随访时间为一年。在每组中，评估肿瘤反应（率、持续时间）、中位生存时间、1年总生存率、安全性和免疫改变。通过对外周血单个核细胞进行非特异性免疫实验室检测来评估免疫：a）植物血凝素诱导的淋巴细胞增殖，b）调节性T细胞（CD4+CD25+）的比例；以及特异性免疫：a）由先前描述的自体热稳定血液衍生物中所含肿瘤相关抗原（TAA）诱导的淋巴细胞增殖。两种治疗诱导的缓解率差异（化疗组与化疗免疫疗法组分别为39.0%和35.0%）无统计学意义。然而，化疗免疫疗法的反应持续时间（22周和31周）、中位生存时间（32周和44周）和1年生存率（33.3%和39.1%）在统计学上更高。两组之间的毒性无差异。化疗免疫疗法治疗与实验室免疫特征（非特异性和特异性）的转变相关：增殖性淋巴细胞反应增加、耐受性调节性T细胞减少以及引发TAA致敏。
