Herberman R B
Cancer Treat Rep. 1985 Oct;69(10):1161-4.
Biological response modifiers (BRMs) include biological and chemical agents which can increase host resistance against tumor growth and also biological agents which can have direct effects on tumor cells, by inducing cytolysis, growth inhibition, and/or differentiation. It is becoming increasingly clear that initial phase I clinical trials with BRMs need to be designed considerably differently from those for chemotherapeutic agents. In addition to determining the toxicity of each agent and its maximal tolerated dose, it is important to evaluate its effects on relevant immunologic and other host responses and to determine the optimal biological response modifying dose (OBRMD). Also, since most BRMs are likely to be effective mainly for treatment of cancer patients with low tumor burdens, and the biological response modifying effects of an agent may vary with the extent of disease, it seems necessary to first perform a phase IA trial in patients with advanced cancer, with an emphasis on determining toxicity and possibly the maximal tolerated dose. Then a phase IB trial will be performed, with patients with minimal or even undetectable tumor burden, to determine the OBRMD. These phase I trials will then allow planning for phase II trials for evaluation of antitumor effects, at doses and in cancer patients which might be expected to be favorable for detection of efficacy.
生物反应调节剂（BRMs）包括能够增强宿主抵抗肿瘤生长能力的生物和化学制剂，以及能够通过诱导细胞溶解、生长抑制和/或分化对肿瘤细胞产生直接作用的生物制剂。越来越明显的是，BRMs的I期临床试验设计需要与化疗药物的I期临床试验有很大不同。除了确定每种制剂的毒性及其最大耐受剂量外，评估其对相关免疫和其他宿主反应的影响并确定最佳生物反应调节剂量（OBRMD）也很重要。此外，由于大多数BRMs可能主要对肿瘤负荷低的癌症患者有效，并且一种制剂的生物反应调节作用可能随疾病程度而变化，因此似乎有必要首先在晚期癌症患者中进行IA期试验，重点是确定毒性以及可能的最大耐受剂量。然后将进行IB期试验，针对肿瘤负荷最小甚至无法检测到的患者，以确定OBRMD。这些I期试验将为II期试验的规划提供依据，以评估在可能有利于检测疗效的剂量下以及在癌症患者中的抗肿瘤效果。
