Raderer M, Scheithauer W
Universitätsklinik für Innere Medizin I, Abteilung für Onkologie, Vienna, Austria.
Eur J Cancer. 1995 Jun;31A(6):1002-8. doi: 10.1016/0959-8049(95)00078-x.
5-Fluorouracil (5-FU) is the most active single agent for treatment of advanced colorectal cancer, although objective responses occur in only 20% of patients, and there seems to be no impact on overall survival. Experimental findings suggesting that interferon-alpha (IFN-alpha) enhances 5-FU cytotoxicity have stimulated an increasing number of clinical trials to evaluate the therapeutic potential of this combination. This article summarises the possible mechanisms of interaction of 5-FU and IFN-alpha, and provides an overview of the current status of this approach in advanced colorectal cancer. A computerised (Medline) and manual search were performed to identify all trials using 5-FU and IFN-alpha for the treatment of advanced colorectal cancer published in the English literature between 1960 and 1994. Information abstracted included treatment regimen, number of patients, pretreatment status, complete and partial remissions, remission duration, overall survival, and toxicity. A total of 417 patients were enrolled in 16 trials using different regimens of 5-FU and IFN-alpha, and double modulation of 5-FU with leucovorin (LV) and IFN-alpha was investigated in nine trials involving 332 patients. The mean overall response rate in these phase II trials was only 31% (range 3-76) and 35% (range 0-54), respectively. Early results of six prospectively randomised studies of 5-FU or 5-FU/LV +/- IFN-alpha also did not suggest a significant enhancement of the antitumour effectiveness with the addition of IFN-alpha. There is increasing evidence, however, that administration of IFN-alpha along with 5-FU enhances toxicity. Because of their modest therapeutic index, currently employed regimens of 5-FU +/- LV plus IFN-alpha cannot be recommended for routine use at the present time. The combination of 5-FU plus LV represents an equally effective and less expensive alternative. Nevertheless, there is still hope that further attempts to elucidate the complex mechanisms of this potentially synergistic drug combination will allow the rational design of regimens with a superior therapeutic index.
5-氟尿嘧啶（5-FU）是治疗晚期结直肠癌最有效的单一药物，尽管只有20%的患者出现客观缓解，而且似乎对总生存期没有影响。实验结果表明，α-干扰素（IFN-α）可增强5-FU的细胞毒性，这促使越来越多的临床试验来评估这种联合用药的治疗潜力。本文总结了5-FU与IFN-α相互作用的可能机制，并概述了这种方法在晚期结直肠癌中的应用现状。通过计算机（Medline）检索和手工检索，以确定1960年至1994年间发表在英文文献中使用5-FU和IFN-α治疗晚期结直肠癌的所有试验。提取的信息包括治疗方案、患者数量、预处理状态、完全缓解和部分缓解、缓解持续时间、总生存期和毒性。共有417例患者参与了16项使用不同5-FU和IFN-α方案的试验，9项涉及332例患者的试验研究了5-FU与亚叶酸（LV）和IFN-α的双重调节。在这些II期试验中，平均总缓解率分别仅为31%（范围3%-76%）和35%（范围0%-54%）。5-FU或5-FU/LV±IFN-α的六项前瞻性随机研究的早期结果也未表明添加IFN-α可显著增强抗肿瘤效果。然而，越来越多的证据表明，IFN-α与5-FU联合使用会增加毒性。由于其治疗指数适中，目前使用的5-FU±LV加IFN-α方案目前不推荐常规使用。5-FU加LV的联合方案是一种同样有效且成本较低的选择。尽管如此，仍有希望进一步阐明这种潜在协同药物组合的复杂机制，从而合理设计出具有更高治疗指数的方案。
