Cook J A, Glass J, Lebovics R, Bobo H, Pass H, DeLaney T F, Oldfield E H, Mitchell J B, Glatstein E, Goffman T E
Radiation Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Cancer Res. 1992 Feb 1;52(3):719-25.
Based upon the radiation sensitization properties of the halogenated pyrimidines, 5-iododeoxyuridine (IdUrd) and 5-bromodeoxyuridine, long term i.v. infusions of halogenated pyrimidines in conjunction with fractionated radiation therapy have been evaluated in the treatment of a variety of human malignancies. While clinical studies have attempted to measure the halogenated pyrimidine incorporation, few have successfully related tumor response to the incorporation of IdUrd by the tumor. The present study reports the continuous IdUrd labeling index (number of cells labeled) and the IdUrd corrected replacement (percentage of thymidine replacement in the labeled cells of the population) from the tumors of 17 patients who received continuous infusions of IdUrd (1000 mg/m2/24 h). The tumors treated included four high grade gliomas, five head and neck tumors, four high grade sarcomas, and five other tumors of varying types. Less than 25% of the cells in three of four gliomas incorporated IdUrd after 5-7-day IdUrd infusion time. Corrected replacement for the gliomas ranged from 0 to 4%. In contrast, 63-85% of the cells in the head and neck biopsies were labeled with IdUrd after 3-7-day IdUrd infusions suggesting that these large tumors (3-12 cm diameter) have a high fraction of dividing cells. Corrected replacements values for the head and neck tumor patients ranged from 2.9 to 26.3%. The high grade sarcomas also demonstrated a high percentage of IdUrd labeled cells (57-79%) with three patients having corrected replacements of 7.5-14.2%. The continuous labeling and thymidine replacement data for four patients from whom serial biopsies were taken during IdUrd infusion demonstrated both an increasing IdUrd replacement and continuous labeling index with an increasing duration of IdUrd infusion. The clinical response of both the high grade glioma and head and neck tumor patients indicate that the IdUrd replacement and labeling data may provide some important predictive information with regard to the successful use of the halogenated pyrimidines in clinical radiation trials.
基于卤代嘧啶、5-碘脱氧尿苷（IdUrd）和5-溴脱氧尿苷的辐射增敏特性，已对长期静脉输注卤代嘧啶联合分次放射治疗在多种人类恶性肿瘤治疗中的应用进行了评估。虽然临床研究试图测量卤代嘧啶的掺入情况，但很少有研究成功地将肿瘤反应与肿瘤对IdUrd的掺入联系起来。本研究报告了17例接受IdUrd持续输注（1000 mg/m²/24 h）患者肿瘤的连续IdUrd标记指数（标记细胞数）和IdUrd校正替代率（群体中标记细胞中胸苷替代的百分比）。所治疗的肿瘤包括4例高级别胶质瘤、5例头颈部肿瘤、4例高级别肉瘤和5例其他不同类型的肿瘤。在IdUrd输注5 - 7天后，4例胶质瘤中有3例的细胞掺入IdUrd的比例不到25%。胶质瘤的校正替代率范围为0%至4%。相比之下，在IdUrd输注3 - 7天后，头颈部活检组织中63% - 85%的细胞被IdUrd标记，这表明这些大肿瘤（直径3 - 12 cm）有很大一部分分裂细胞。头颈部肿瘤患者的校正替代率值范围为2.9%至26.3%。高级别肉瘤也显示出高比例的IdUrd标记细胞（57% - 79%），3例患者的校正替代率为7.5% - 14.2%。在IdUrd输注期间进行系列活检的4例患者的连续标记和胸苷替代数据显示，随着IdUrd输注时间的延长，IdUrd替代率和连续标记指数均增加。高级别胶质瘤和头颈部肿瘤患者的临床反应表明，IdUrd替代和标记数据可能为卤代嘧啶在临床放射试验中的成功应用提供一些重要的预测信息。
