Pazdur R, Ajani J A, Patt Y Z, Winn R, Jackson D, Shepard B, DuBrow R, Campos L, Quaraishi M, Faintuch J
Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston 77030.
J Clin Oncol. 1990 Dec;8(12):2027-31. doi: 10.1200/JCO.1990.8.12.2027.
We conducted a phase II clinical trial of fluorouracil (5FU) and recombinant interferon alfa-2a (rIFN alpha-2a) in 52 previously untreated patients with bidimensionally measurable metastatic colorectal cancer. During week 1, 5FU was administered as a continuous intravenous infusion, 750 mg/m2/d for 5 consecutive days. Intravenous bolus administration of 5FU 750 mg/m2 was given weekly for 7 weeks starting on day 12. rIFN alpha-2a (Roferon; Hoffman-LaRoche, Nutley, NJ), 9 x 10(6) U, was administered subcutaneously three times weekly during weeks 1 to 8. Patients were evaluated for response on week 9. Of 52 patients enrolled in the study, 51 were assessable for toxicity, and 45 were assessable for response. Fifteen patients experienced partial response, and one patient achieved a clinical complete response for an overall response rate of 35% (95% confidence interval [CI], 22%, 50%). Median duration of response is 7.5 months (range, 4 to 11 months). Seventy percent of patients entered on the study are alive with a median follow-up duration of 7 months. Twenty-five percent of patients developed grade 4 toxicity, and 82% developed grade 3 toxicity. One drug-related death in the presence of sepsis was reported, and two treatment-related seizures occurred. Our experience with this schedule produced a lower response rate with greater toxicity than previously reported. Current randomized trials comparing this schedule of 5FU with rIFN alpha-2a to 5FU plus folinic acid (leucovorin) or single-agent 5FU may determine its role in the treatment of advanced colorectal carcinomas.
我们对52例先前未经治疗的二维可测量转移性结直肠癌患者进行了氟尿嘧啶（5FU）和重组干扰素α-2a（rIFNα-2a）的II期临床试验。在第1周，5FU通过持续静脉输注给药，750mg/m²/天，连续5天。从第12天开始，每周静脉推注5FU 750mg/m²，共7周。rIFNα-2a（罗扰素；霍夫曼-罗氏公司，新泽西州纳特利），9×10⁶U，在第1至8周每周皮下注射三次。在第9周对患者的反应进行评估。在纳入研究的52例患者中，51例可评估毒性，45例可评估反应。15例患者出现部分缓解，1例患者达到临床完全缓解，总缓解率为35%（95%置信区间[CI]，22%，50%）。中位缓解持续时间为7.5个月（范围，4至11个月）。进入该研究的患者中有70%存活，中位随访时间为7个月。25%的患者出现4级毒性，82%的患者出现3级毒性。报告了1例在存在败血症情况下与药物相关的死亡，以及2例与治疗相关的癫痫发作。我们使用该方案的经验显示，与先前报道相比，缓解率较低且毒性更大。目前正在进行的将5FU与rIFNα-2a的这一方案与5FU加亚叶酸（甲酰四氢叶酸）或单药5FU进行比较的随机试验，可能会确定其在晚期结直肠癌治疗中的作用。
