Otto F, Schmid P, Mackensen A, Wehr U, Seiz A, Braun M, Galanos C, Mertelsmann R, Engelhardt R
Medizinische Klinik I der Albert-Ludwig-Universität, Germany.
Eur J Cancer. 1996 Sep;32A(10):1712-8. doi: 10.1016/0959-8049(96)00186-4.
We report the immunological and clinical results of a phase II trial with intravenously administered highly purified endotoxin (Salmonella abortus equi) in patients with advanced cancer. 15 patients with non-small cell lung cancer and 27 with colorectal cancer were entered into the study. 37 evaluable patients received at least four injections of endotoxin (4 ng/kg body weight) and 1600 mg ibuprofen orally in 2-week intervals. Transient renal (WHO grade 0-1) and hepatic (WHO grade 0-4) toxicities occurred in several patients. Constitutional side-effects such as fever, chills and hypotension could not be prevented completely by pretreatment with ibuprofen. 3 patients in the colorectal cancer group demonstrated objective responses (1 complete remission (CR), 2 partial remission (PR)). The complete remission has been maintained for more than 3 years, while the partial remissions were stable for 7 and 8 months, respectively. Only marginal antitumour effects were seen in the lung cancer group. Tolerance of the macrophage system to the stimulatory effect of endotoxin, as measured by human necrosis factor alpha (TNF-alpha) release into serum, built up after the first administration and remained at a steady-state level after each subsequent injection. In constrast, rising CD4:CD8 ratio and release of tumour necrosis factor beta (TNF-beta) indicated the continuing activation of the lymphocyte system by repetitive injections of endotoxin.
我们报告了一项针对晚期癌症患者静脉注射高纯度内毒素（马流产沙门氏菌）的II期试验的免疫学和临床结果。15例非小细胞肺癌患者和27例结直肠癌患者进入该研究。37例可评估患者接受了至少四次内毒素注射（4 ng/kg体重），并每2周口服1600 mg布洛芬。数名患者出现了短暂性肾脏毒性（世界卫生组织0 - 1级）和肝脏毒性（世界卫生组织0 - 4级）。布洛芬预处理并不能完全预防发热、寒战和低血压等全身性副作用。结直肠癌组有3例患者出现客观缓解（1例完全缓解（CR），2例部分缓解（PR））。完全缓解已持续超过3年，而部分缓解分别稳定了7个月和8个月。肺癌组仅观察到微弱的抗肿瘤作用。通过血清中人肿瘤坏死因子α（TNF-α）释放量来衡量，巨噬细胞系统对内毒素刺激作用的耐受性在首次给药后建立，并在随后每次注射后维持在稳态水平。相比之下，CD4:CD8比值升高和肿瘤坏死因子β（TNF-β）释放表明淋巴细胞系统因重复注射内毒素而持续激活。
