Lümmen G, Sperling H, Luboldt H, Otto T, Rübben H
Department of Urology, University of Essen Medical School, Essen, Germany.
Urol Int. 1998;61(4):215-9. doi: 10.1159/000030332.
Biological response modifiers such as interferon-alpha2B (IFN-alpha2B) have well-known clinical activities against renal cell carcinoma (RCC). Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) has antitumorigenic effects both in vitro and in vivo. Therefore, a phase-I/II trial of IFN-alpha2B and GM-CSF was performed in patients with metastatic RCC.
21 patients in groups of 3 patients received GM-CSF at 7 different dose levels (15-300 microg) subcutaneously in combination with IFN-alpha2B at a fixed dose of 10 x 10(6) IU s.c. three times weekly for 12 weeks.
Two complete remissions have been observed, both with lung metastases only. With increasing dose levels of GM-CSF a slight tendency to more toxicity was detectable. Due to grade-3 toxicities 5 patients (24%) dropped out of the treatment schedule. Increases in WBC, neutrophils, lymphocytes, and monocytes were noted but were not related to the dose levels of GM-CSF.
Results demonstrate that simultaneous administration of GM-CSF and IFN-alpha2B is tolerated up to doses of 120-150 microg GM-CSF three times weekly. But there is no additional antitumorigenic effect of GM-CSF because the overall response rate of the combined administration of GM-CSF/IFN-alpha2B is similar to IFN-alpha2B alone and there is no obvious dose relationship between increasing doses of GM-CSF and the responses.
生物反应调节剂如干扰素-α2B（IFN-α2B）对肾细胞癌（RCC）具有众所周知的临床活性。重组人粒细胞-巨噬细胞集落刺激因子（GM-CSF）在体外和体内均具有抗肿瘤作用。因此，对转移性RCC患者进行了IFN-α2B和GM-CSF的I/II期试验。
21例患者分为3人一组，接受7种不同剂量水平（15 - 300微克）的GM-CSF皮下注射，联合固定剂量为10×10(6)国际单位的IFN-α2B皮下注射，每周3次，共12周。
观察到2例完全缓解，均仅伴有肺转移。随着GM-CSF剂量水平的增加，可检测到毒性略有增加的趋势。由于3级毒性，5例患者（24%）退出治疗方案。观察到白细胞、中性粒细胞、淋巴细胞和单核细胞增加，但与GM-CSF的剂量水平无关。
结果表明，每周3次同时给予GM-CSF和IFN-α2B，GM-CSF剂量高达120 - 150微克时耐受性良好。但GM-CSF没有额外的抗肿瘤作用，因为GM-CSF/IFN-α2B联合给药的总缓解率与单独使用IFN-α2B相似，且GM-CSF剂量增加与反应之间没有明显的剂量关系。
