Ohnuma T
Dept. of Neoplastic Diseases, Derald Ruttenberg Cancer Center, Mount Sinai Medical Center, New York.
Gan To Kagaku Ryoho. 1990 Aug;17(8 Pt 1):1428-36.
Such biological response modifiers (BRMs) as interferon, interleukin-2 and tumor necrosis factor were shown to have some antitumor activity in man. In addition, preclinical studies have demonstrated favorable interactions of these BRMs and chemotherapeutic agents. Animal studies have shown cure in certain combinations. Therefore, it has become important to study whether combinations of these BRMs and chemotherapeutic agents would increase response rate, survival and/or the quality of life in patients with cancer. In this review entire articles on this subject published in English literature were evaluated to assess current status. While there were isolated articles describing improved response rates, a majority of articles failed to document clinical benefit from the combinations. Some articles recorded increased toxicity without therapeutic benefit. At this time there was only one published phase III study comparing chemotherapy and the chemotherapy combined with BRM, in this case interferon: response rate and survival were identical in the two groups. The review of these articles resulted in identification of several factors considered to be associated with the discrepancy between preclinical data vs. clinical results: larger tumor load in man as compared to animals, importance of pharmacokinetic barrier which can not be incorporated in in vitro systems, differences in dosing schedules between animals and man, and differences in assessing response. Presence of negative preclinical data can not also be ignored. It is concluded that in order for better assessment of this modality of treatment further phase III studies are needed. Therapeutic effects may improve if dose scheduling are optimized and patients with small tumor load are studied preferentially.
诸如干扰素、白细胞介素 -2 和肿瘤坏死因子等生物反应调节剂（BRM）已被证明在人体中具有一定的抗肿瘤活性。此外，临床前研究表明这些 BRM 与化疗药物之间存在有益的相互作用。动物研究显示某些联合用药可治愈肿瘤。因此，研究这些 BRM 与化疗药物的联合使用是否能提高癌症患者的缓解率、生存率和 / 或生活质量变得至关重要。在本综述中，对英文文献中发表的关于该主题的所有文章进行了评估，以评估当前的研究现状。虽然有个别文章描述了缓解率有所提高，但大多数文章未能证明联合用药具有临床益处。一些文章记录了毒性增加但无治疗益处。目前仅有一项已发表的 III 期研究比较了化疗与化疗联合 BRM（在本研究中为干扰素）的疗效：两组的缓解率和生存率相同。对这些文章的综述确定了几个被认为与临床前数据和临床结果之间差异相关的因素：与动物相比，人类肿瘤负荷更大；体外系统无法纳入的药代动力学屏障的重要性；动物与人给药方案的差异；以及评估反应的差异。临床前负面数据的存在也不容忽视。结论是，为了更好地评估这种治疗方式，需要进一步开展 III 期研究。如果优化给药方案并优先研究肿瘤负荷小的患者，治疗效果可能会改善。
