Dufour P, Husseini F, Dreyfus B, Cure H, Martin C, Prevost G, Olivier J P, Dumas F, Duclos B, Olivares R, Leszler A, Bergerat J P, Audhuy B, Thill L, Oberling F
Département d'Oncologie, Hôpitaux Universitaires de Strasbourg, France.
Ann Oncol. 1996 Aug;7(6):575-9. doi: 10.1093/oxfordjournals.annonc.a010673.
In 1989, S. Wadler reported very promising results (76% response rate) with a combination of 5-fluorouracil (5-FU) plus alpha-2a interferon (IFN) in the treatment of metastatic colorectal carcinoma (MCRC). In vitro, there are several potential explanations for synergism between the two agents. We therefore decided in 1989 to start a randomized study comparing 5-FU alone with 5-FU plus IFN.
105 non-pretreated patients with measurable metastatic colorectal carcinoma entered into this study. The patients were randomly allocated either in arm A (n = 49) with 5-FU: 750 mg/m2 i.v. CI d1-d5 followed by 750 mg/m2 i.v. bolus once a week, or in arm B (n = 56) with 5-FU as in arm A plus IFN 9 x 10(6) IU sub-cutaneously three times a week.
After two months of treatment we observed 1 CR and 2 PR in arm A (response rate 6.1%), 3 CR and 8 PR in arm B (response rate 19.6%), i.e., a significant difference (P = 0.05). Event-free survival was significantly higher in arm B (6 months) than in arm A (2 months) (P < 0.01), while median survival was slightly higher in arm B (12 months) than in arm A (10 months) (P < 0.05). For overall survival the difference was not significant after adjustment on center treatment and baseline Karnofsky status (P = 0.13). Toxicity was also greater in arm B. Sixteen percent of patients in arm A and 36% in arm B experienced certain grade 3-4 side effects (P < 0.05).
5-FU plus IFN is more effective than 5-FU alone in terms of response rate, event free survival but not of overall survival. 5-FU plus IFN is more toxic. As IFN has no demonstrated efficacy in MCRC as a single agent, this study suggests that IFN is acting as a 5-FU modulatory agent. The response rate observed (19.6%) is similar to the results obtained elsewhere with 5-FU plus leucovorin.
1989年，S. 瓦德勒报告了5-氟尿嘧啶（5-FU）联合α-2a干扰素（IFN）治疗转移性结直肠癌（MCRC）取得了非常有前景的结果（缓解率76%）。在体外，对于这两种药物之间的协同作用有几种潜在的解释。因此，我们在1989年决定开展一项随机研究，比较单纯5-FU与5-FU加IFN的疗效。
105例未经预处理的可测量转移性结直肠癌患者进入本研究。患者被随机分配到A组（n = 49），接受5-FU治疗：750 mg/m²静脉持续输注第1 - 5天，随后每周一次750 mg/m²静脉推注；或B组（n = 56），接受与A组相同的5-FU治疗，外加每周三次皮下注射IFN 9×10⁶ IU。
治疗两个月后，我们观察到A组有1例完全缓解（CR）和2例部分缓解（PR）（缓解率6.1%），B组有3例CR和8例PR（缓解率19.6%），即有显著差异（P = 0.05）。B组的无事件生存期（6个月）显著高于A组（2个月）（P < 0.01），而B组的中位生存期（12个月）略高于A组（10个月）（P < 0.05）。在对中心治疗和基线卡诺夫斯基状态进行调整后，总生存期的差异不显著（P = 0.13）。B组的毒性也更大。A组16% 的患者和B组36% 的患者出现了某些3 - 4级副作用（P < 0.05）。
就缓解率和无事件生存期而言，5-FU加IFN比单纯5-FU更有效，但总生存期并非如此。5-FU加IFN毒性更大。由于IFN作为单一药物在MCRC中未显示出疗效，本研究表明IFN起到了5-FU调节剂的作用。观察到的缓解率（19.6%）与其他地方使用5-FU加亚叶酸所获得的结果相似。
