Rougier P, Van Cutsem E, Bajetta E, Niederle N, Possinger K, Labianca R, Navarro M, Morant R, Bleiberg H, Wils J, Awad L, Herait P, Jacques C
Institute Gustave Roussy, Villejuif, France.
Lancet. 1998 Oct 31;352(9138):1407-12. doi: 10.1016/S0140-6736(98)03085-2.
In phase II trials, irinotecan is active in patients with advanced colorectal cancer, but the survival and clinical benefit of irinotecan compared with second-line fluorouracil by continuous infusion is not known.
267 patients who had failed to respond to first-line fluorouracil, or whose disease had progressed after treatment with first-line fluorouracil were randomly allocated irinotecan 300-350 mg/m2 infused once every 3 weeks or fluorouracil by continuous infusion. Treatment was given until disease progression, unacceptable toxic effects, or the patient refused to continue treatment. The primary endpoint was survival, while progression-free survival, response rate, symptom-free survival, adverse events, and quality of life (QoL) were secondary endpoints.
133 patients were randomly allocated irinotecan and 134 were allocated fluorouracil by continuous infusion. Patients treated with irinotecan lived for significantly longer than patients on fluorouracil (p=0.035). Survival at 1 year was increased from 32% in the fluorouracil group to 45% in the irinotecan group. Median survival was 10.8 months in the irinotecan group and 8.5 months in the fluorouracil group. Median progression-free survival was longer with irinotecan (4.2 vs 2.9 months for irinotecan vs fluorouracil, respectively; p=0.030). The median pain-free survival was 10.3 months and 8.5 months (p=0.06) for irinotecan and fluorouracil, respectively. Both treatments were equally well tolerated. QoL was similar in both groups.
Compared with fluorouracil by continuous infusion second-line irinotecan significantly improved survival in patients with advanced colorectal cancer.
在II期试验中，伊立替康对晚期结直肠癌患者有活性，但与持续输注二线氟尿嘧啶相比，伊立替康的生存情况及临床获益尚不清楚。
267例对一线氟尿嘧啶无反应或一线氟尿嘧啶治疗后疾病进展的患者被随机分配接受每3周一次静脉输注300 - 350mg/m²伊立替康或持续输注氟尿嘧啶。治疗持续至疾病进展、出现不可接受的毒性作用或患者拒绝继续治疗。主要终点为生存，无进展生存期、缓解率、无症状生存期、不良事件及生活质量（QoL）为次要终点。
133例患者被随机分配接受伊立替康治疗，134例患者被分配接受持续输注氟尿嘧啶治疗。接受伊立替康治疗的患者生存时间显著长于接受氟尿嘧啶治疗的患者（p = 0.035）。1年生存率从氟尿嘧啶组的32%提高到伊立替康组的45%。伊立替康组的中位生存期为10.8个月，氟尿嘧啶组为8.5个月。伊立替康的中位无进展生存期更长（伊立替康组与氟尿嘧啶组分别为4.2个月和2.9个月；p = 0.030）。伊立替康和氟尿嘧啶的中位无痛生存期分别为10.3个月和8.5个月（p = 0.06）。两种治疗的耐受性相当。两组的生活质量相似。
与持续输注氟尿嘧啶相比，二线伊立替康显著提高了晚期结直肠癌患者的生存率。
