Wolf M, Maasberg M, Pfab R, Havemann K
Philipps University, Department of Internal Medicine, Marburg, Federal Republic of Germany.
J Cancer Res Clin Oncol. 1991;117 Suppl 4(Suppl 4):S187-92. doi: 10.1007/BF01613225.
The combination of radiotherapy and cytostatic drugs is of interest in the treatment of several solid tumors. In these preclinical investigations we tested whether ifosfamide and ACNU are able to enhance radiation effects. The experiments were performed by using the MTT assay. Two small cell and 2 non small cell lung cancer cell lines were involved. Ifosfamide, ACNU or both drugs together were tested in 6 different concentrations adjusted to the peak blood level. During the 1 hour drug incubation time, the cell lines were either irradiated with a single dose of 4 Gy or not. The main results were that ACNU possessed only little cytostatic activity in the cell lines under examination. In contrast, ifosfamide caused a dose related cytostatic activity in all cell lines. Concentrations of 26 micrograms/ml (NCC-SCLC H 82) or 10-12 micrograms/ml (3 other cell lines) were able to reduce the surviving cell fraction to less than 50% (IC50). While ACNU showed no clear outlined radiosensitizing properties, ifosfamide reinforced the radiation effects in 3 out of 4 cell lines indicating radiosensitizing properties of this drug. Synergistic effects of ifosfamide and ACNU have not been noticed. These preclinical investigations may constitute the basis for combined ifosfamide and irradiation therapy in future clinical trials.
放射疗法与细胞抑制药物联合使用在多种实体瘤的治疗中备受关注。在这些临床前研究中，我们测试了异环磷酰胺和阿糖胞苷是否能够增强放射效应。实验采用MTT法进行。研究涉及两种小细胞肺癌细胞系和两种非小细胞肺癌细胞系。异环磷酰胺、阿糖胞苷或两种药物联合使用，以6种不同浓度进行测试，这些浓度根据血药峰值进行调整。在1小时的药物孵育期间，细胞系分别接受4 Gy的单次照射或不照射。主要结果如下：在所检测的细胞系中，阿糖胞苷仅具有微弱的细胞抑制活性。相比之下，异环磷酰胺在所有细胞系中均呈现剂量相关的细胞抑制活性。浓度为26微克/毫升（NCC - SCLC H 82）或10 - 12微克/毫升（其他3种细胞系）能够将存活细胞分数降低至50%以下（IC50）。虽然阿糖胞苷未表现出明显的放射增敏特性，但异环磷酰胺在4种细胞系中的3种中增强了放射效应，表明该药物具有放射增敏特性。未观察到异环磷酰胺和阿糖胞苷的协同效应。这些临床前研究可能为未来临床试验中异环磷酰胺与放射治疗的联合应用奠定基础。
