Khoo S K, Hurst T, Webb M J, Dickie G, Kearsley J, Parsons P G, Mackay E V
Department of Obstetrics and Gynaecology, University of Queensland, Australia.
J Surg Oncol. 1989 Jul;41(3):201-5. doi: 10.1002/jso.2930410314.
The hypothesis that in vitro chemosensitivity testing could predict clinical outcome was tested in women with ovarian cancer. Short-term drug effects on DNA and RNA metabolism (by inhibition of 3H-thymidine and 3H-uridine incorporation) were measured in primary cultures of tumor cells. In vitro inhibitory effects were found with the four drugs tested: cisplatin, adriamycin, melphalan, and methotrexate. From data based on impaired RNA and/or DNA metabolism (greater than or equal to 20% inhibition), correct prediction of "sensitivity" was 79% and that of "resistance" was 84%. An analysis of the predictive value of both assays, used singly or together, revealed a high specificity but moderate sensitivity; the best positive predictive value (94%) was obtained when both RNA and DNA metabolisms were impaired. Our results support the idea that two subsets of patients who are being considered for cytotoxic chemotherapy can be selected; those who may benefit from treatment and those who may not, regardless of the drugs tested in vitro or used in vivo.
关于体外化学敏感性测试能否预测卵巢癌女性患者临床结果的假说进行了验证。在肿瘤细胞原代培养中测量了药物对DNA和RNA代谢的短期影响(通过抑制³H-胸腺嘧啶核苷和³H-尿苷掺入)。在所测试的四种药物(顺铂、阿霉素、美法仑和甲氨蝶呤)中发现了体外抑制作用。基于RNA和/或DNA代谢受损(抑制率大于或等于20%)的数据,对“敏感性”的正确预测率为79%,对“耐药性”的正确预测率为84%。对单独或联合使用的两种检测方法的预测价值进行分析,结果显示特异性高但敏感性中等;当RNA和DNA代谢均受损时,获得了最佳的阳性预测值(94%)。我们的结果支持这样一种观点,即可以选择两类考虑进行细胞毒性化疗的患者;一类可能从治疗中获益,另一类可能无法获益,无论体外测试的药物或体内使用的药物是什么。