Simon R, Korn E L
Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
J Natl Cancer Inst. 1990 Sep 19;82(18):1469-76. doi: 10.1093/jnci/82.18.1469.
We describe a mathematical model for selecting cytotoxic drugs and dosages for a combination regimen based on the antitumor activities of the drugs given as single agents and their organ-specific maximum tolerated doses. The regimen defined maximizes an approximate measure of antitumor effect subject to constraints on combined toxicity. This approach does not assume that the underlying dose-response curve is steep; nor does it assume that maximally dose-intense regimens are clinically appropriate in all situations. Whether the identified regimen is superior to standard treatments should be determined by prospective, randomized clinical trials. Determining which drugs to combine and in what proportions to combine them offers combinatorially huge numbers of possibilities. The method described here offers one approach to identifying combinations worthy of evaluation in prospective trials.
我们描述了一种数学模型，该模型可根据作为单一药物给药时的抗肿瘤活性及其器官特异性最大耐受剂量，为联合治疗方案选择细胞毒性药物和剂量。所定义的治疗方案在联合毒性的限制下，使抗肿瘤效果的近似度量最大化。这种方法既不假设潜在的剂量反应曲线是陡峭的，也不假设在所有情况下最大剂量强度的治疗方案在临床上都是合适的。所确定的治疗方案是否优于标准治疗应通过前瞻性随机临床试验来确定。确定将哪些药物联合使用以及以何种比例联合使用会产生组合上大量的可能性。这里描述的方法提供了一种识别值得在前瞻性试验中评估的联合方案的途径。
