Engelhardt R, Mackensen A, Galanos C
Medizinische Klinik I, Albert-Ludwigs-Universität, Freiburg, Federal Republic of Germany.
Cancer Res. 1991 May 15;51(10):2524-30.
We report a phase I study in cancer patients being treated with i.v. bolus injections of highly purified lipopolysaccharide (LPS) Salmonella abortus equi. Twenty-four patients with disseminated cancer received escalating doses of LPS at 2-week intervals. Dose escalation was performed in six dose levels treating 3-6 patients at each level. Dose levels 1 and 2 consisted of 0.15 and 0.3 ng/kg, respectively. Further dose escalation up to 5.0 ng/kg was enabled by pretreatment with ibuprofen, which attenuated the constitutional side effects of LPS. The maximum tolerated dose was 4.0 ng/kg with dose-limiting toxicity being World Health Organization grade III hepatic toxicity. Hematological changes included transient decreases in WBCs affecting granulocytes, monocytes, and lymphocytes in a marked different pattern. Endogenous cytokine release occurred in an LPS dose-dependent manner as measured by tumor necrosis factor-alpha, interleukin-6, and macrophage colony-stimulating factor serum levels. Moderate antitumor activity in colorectal cancer was observed in the case of 2 patients. Phase II trials of LPS are currently in progress.
我们报告了一项针对癌症患者的I期研究，这些患者接受静脉推注高纯度流产马流产沙门氏菌脂多糖（LPS）治疗。24例播散性癌症患者每隔2周接受递增剂量的LPS治疗。剂量递增分六个剂量水平进行，每个水平治疗3 - 6例患者。剂量水平1和2分别为0.15和0.3 ng/kg。通过布洛芬预处理实现了进一步剂量递增至5.0 ng/kg，布洛芬减轻了LPS的全身副作用。最大耐受剂量为4.0 ng/kg，剂量限制性毒性为世界卫生组织III级肝毒性。血液学变化包括白细胞短暂减少，以明显不同的模式影响粒细胞、单核细胞和淋巴细胞。通过肿瘤坏死因子-α、白细胞介素-6和巨噬细胞集落刺激因子血清水平测定，内源性细胞因子释放呈LPS剂量依赖性。2例患者的结直肠癌出现中度抗肿瘤活性。LPS的II期试验目前正在进行中。
