亚叶酸钙对大剂量输注氟尿嘧啶进行有效生物调节（氟尿嘧啶每周24小时输注）：晚期结直肠癌患者的一项随机试验结果

Effective biomodulation by leucovorin of high-dose infusion fluorouracil given as a weekly 24-hour infusion: results of a randomized trial in patients with advanced colorectal cancer.

作者信息

Köhne C H, Schöffski P, Wilke H, Käufer C, Andreesen R, Ohl U, Klaasen U, Westerhausen M, Hiddemann W, Schott G, Harstick A, Bade J, Horster A, Schubert U, Hecker H, Dörken B, Schmoll H J

机构信息

Department of Haematology/Oncology and Tumor Immunology, Robert-Rössle-Klinik, Berlin, Germany.

出版信息

J Clin Oncol. 1998 Feb;16(2):418-26. doi: 10.1200/JCO.1998.16.2.418.

DOI:10.1200/JCO.1998.16.2.418

PMID:9469324

Abstract

PURPOSE

To determine whether high-dose infusional fluorouracil (FU) is effectively modulated by leucovorin (LV), interferon (IFN) alpha-2b, or both when given to patients with metastatic colorectal cancer.

PATIENTS AND METHODS

Patients (n = 236) with progressive, measurable disease were randomized to three groups and received FU 2,600 mg/m2 as a 24-hour continuous infusion (CI) weekly for 6 weeks with 2 weeks rest (FU24h) and LV 500 mg/m2 as a 2-hour infusion before FU or IFN 3 x 10(6) U subcutaneously 3 times weekly or both. Treatment continued until progressive disease or unacceptable toxicity was observed. Pairs of treatment arms were analyzed sequentially to detect equivalence or a 25% difference in response rates.

RESULTS

The rate of objective remission in patients who received FU24h/LV (44%; 40 of 91) was significantly higher than in patients who received FU24h/IFN (18%; 16 of 90; P < .05). The response rates of patients who received FU24h/LV versus FU24h/LV/IFN (27%; 13 of 49) were statistically equivalent. Significant differences were observed for time to tumor progression (TTP) (FU24h/LV, 7.1 months; FU24h/IFN, 3.9 months; FU24h/LV/IFN, 6.3 months; global P value < .009) and survival (16.6 months, 12.7 months, 19.6 months, respectively; global P value < .04). Unpredictable and life-threatening toxicity in the FU24h/LV/IFN arm required dose reduction of FU to 2,000 mg/m2/day and early stoppage of this arm. Toxicity was manageable in patients who received both FU24h/LV (grade 3 to 4 diarrhea, 21%) and FU24h/IFN (grade 3 to 4 diarrhea, 15%).

CONCLUSION

Response rate, TTP, and overall survival were superior for LV-containing regimens compared with IFN modulation alone. The addition of IFN to high-dose infusional FU plus LV offers no advantage and may increase toxicity. The regimen of high-dose infusional FU24h/LV warrants further evaluation in patients with metastatic colorectal cancer.

摘要

目的

确定当给予转移性结直肠癌患者大剂量输注氟尿嘧啶（FU）时，亚叶酸钙（LV）、干扰素（IFN）α-2b或两者联合使用是否能有效调节FU。

患者和方法

236例病情进展且可测量的患者被随机分为三组，接受FU 2600mg/m²，以24小时持续输注（CI）方式每周一次，共6周，休息2周（FU24h），并在输注FU前2小时输注LV 500mg/m²，或每周皮下注射IFN 3×10⁶U，每周3次，或两者联合使用。治疗持续至观察到病情进展或出现不可接受的毒性。对成对的治疗组进行序贯分析，以检测缓解率的等效性或25%的差异。

结果

接受FU24h/LV的患者客观缓解率（44%；91例中的40例）显著高于接受FU24h/IFN的患者（18%；90例中的16例；P<.05）。接受FU24h/LV与FU24h/LV/IFN治疗的患者缓解率（27%；49例中的13例）在统计学上相当。在肿瘤进展时间（TTP）方面观察到显著差异（FU24h/LV为7.1个月；FU24h/IFN为3.9个月；FU24h/LV/IFN为6.3个月；总体P值<.009）和生存率（分别为16.6个月、12.7个月、19.6个月；总体P值<.04）。FU24h/LV/IFN组出现不可预测且危及生命的毒性，需要将FU剂量减至2000mg/m²/天，并提前停止该组治疗。接受FU24h/LV（3至4级腹泻，21%）和FU24h/IFN（3至4级腹泻，15%）的患者毒性是可控的。