Livingston R B
Division of Oncology, University of Washington School of Medicine, Seattle 98195.
Anticancer Res. 1994 Jan-Feb;14(1B):255-60.
Radiation therapy may be made more effective for SCLC by modifying dose fractionation, based on laboratory observation that SCLC cell lines are often relatively deficient in the ability to recover from doses of 2 Gy or less. Results of this approach will be known within a year. Radiation damage to the lungs may be reduced through the use of agents like PTX which can inhibit production of TNF, a likely initial mediator of radiation-related toxicity. Chemotherapy effectiveness may be improved by building on the observation that etoposide is a schedule dependent drug for SCLC lines, now confirmed in part by clinical trials. The ability to detect low orders of contamination by SCLC cells in marrow or blood should make possible more rational evaluation of outcome in protocols that utilize highdose chemotherapy plus autologous blood products as a consolidation maneuver. The monoclonal antibodies which permit this detection may themselves be of value in "purging" unwanted tumor cells from these collections. It may soon become practical to eliminate amplified genes which are associated with drug resistance and/or confer a further growth advantage on tumor cells, through the use of agents like hydroxyurea that can selectively eliminate extrachromosomal DNA. The role of recombinant hematopoietic growth factors in SCLC treatment remains unclear at present. Applying the lessons of molecular biology, it may become possible to promote "differentiation" of SCLC, or at least to prevent its conversion to the variant phenotype associated with increased c-myc expression, with the use of trans-RA or related compounds. "Broad-spectrum" antagonists of neuropeptide function may be effective and relatively specific inhibitors of autocrine stimulation in SCLC, but toxicity is yet unknown. Finally, biologic response modification may be of use in patients who have had their initial tumor burden reduced by standard therapy, utilizing IL-2 (if it can be made less toxic) or monoclonal antibodies conjugated to a toxin or radioemitter (if they can be made more specific).
基于实验室观察结果，即小细胞肺癌细胞系通常在从2 Gy或更低剂量辐射中恢复的能力方面相对不足，通过调整剂量分割方式，放射治疗对小细胞肺癌可能会更有效。这种方法的结果将在一年内知晓。通过使用如紫杉醇（PTX）等药物可以减少肺部的辐射损伤，紫杉醇能够抑制肿瘤坏死因子（TNF）的产生，而TNF可能是辐射相关毒性的初始介质。依托泊苷是一种对小细胞肺癌细胞系具有时间依赖性的药物，这一观察结果现已部分得到临床试验的证实，在此基础上，化疗效果可能会得到改善。在利用高剂量化疗加自体血液制品作为巩固手段的方案中，能够检测骨髓或血液中小细胞肺癌细胞低水平污染的能力，应该会使对治疗结果的评估更加合理。能够进行这种检测的单克隆抗体本身可能在从这些采集物中“清除”不需要的肿瘤细胞方面具有价值。通过使用如羟基脲等能够选择性消除染色体外DNA的药物，消除与耐药性相关或赋予肿瘤细胞进一步生长优势的扩增基因可能很快会成为现实。目前，重组造血生长因子在小细胞肺癌治疗中的作用仍不清楚。应用分子生物学的经验教训，使用全反式维甲酸（trans-RA）或相关化合物，可能会促进小细胞肺癌的“分化”，或者至少防止其转变为与c-myc表达增加相关的变异表型。神经肽功能的“广谱”拮抗剂可能是小细胞肺癌自分泌刺激的有效且相对特异性的抑制剂，但毒性尚不清楚。最后，生物反应调节剂可能对那些通过标准治疗使初始肿瘤负荷降低的患者有用，可利用白细胞介素-2（如果能降低其毒性）或与毒素或放射性发射体偶联的单克隆抗体（如果能使其更具特异性）。
