Cunningham D, Pyrhönen S, James R D, Punt C J, Hickish T F, Heikkila R, Johannesen T B, Starkhammar H, Topham C A, Awad L, Jacques C, Herait P
Royal Marsden Hospital, Sutton, Surrey, UK.
Lancet. 1998 Oct 31;352(9138):1413-8. doi: 10.1016/S0140-6736(98)02309-5.
In phase II studies, irinotecan is active in metastatic colorectal cancer, but the overall benefit has not been assessed in a randomised clinical trial.
Patients with proven metastatic colorectal cancer, which had progressed within 6 months of treatment with fluorouracil, were randomly assigned either 300-350 mg/m2 irinotecan every 3 weeks with supportive care or supportive care alone, in a 2:1 ratio.
189 patients were allocated irinotecan and supportive care and 90 supportive care alone. The mean age of the participants was 58.8 years; 181 (65%) were men and 98 (35%) were women. WHO performance status was 0 in 79 (42%) patients, 1 in 77 (41%) patients, and 2 in 32 (17%) patients. Tumour-related symptoms were present in 134 (71%) patients and weight loss of more than 5% was seen in 15 (8%) patients. With a median follow-up of 13 months, the overall survival was significantly better in the irinotecan group (p=0.0001), with 36.2% 1-year survival in the irinotecan group versus 13.8% in the supportive-care group. The survival benefit, adjusted for prognostic factors in a multivariate analysis, remained significant (p=0.001). Survival without performance-status deterioration (p=0.0001), without weight loss of more than 5% (p=0.018), and pain-free survival (p=0.003) were significantly better in the patients given irinotecan. In a quality-of-life analysis, all significant differences, except on diarrhoea score, were in favour of the irinotecan group.
Our study shows that despite the side-effects of treatment, patients who have metastatic colorectal cancer, and for whom fluorouracil has failed, have a longer survival, fewer tumour-related symptoms, and a better quality of life when treated with irinotecan than with supportive care alone.
在II期研究中，伊立替康对转移性结直肠癌有效，但尚未在随机临床试验中评估其总体获益情况。
确诊为转移性结直肠癌且在接受氟尿嘧啶治疗6个月内病情进展的患者，按2:1的比例随机分配，分别接受每3周一次300 - 350 mg/m²伊立替康联合支持治疗或单纯支持治疗。
189例患者被分配接受伊立替康联合支持治疗，90例患者接受单纯支持治疗。参与者的平均年龄为58.8岁；181例（65%）为男性，98例（35%）为女性。世界卫生组织（WHO）体能状态评分为0分的患者有79例（42%），评分为1分的患者有77例（41%），评分为2分的患者有32例（17%）。134例（71%）患者存在肿瘤相关症状，15例（8%）患者体重减轻超过5%。中位随访13个月时，伊立替康组的总生存期显著更好（p = 0.0001），伊立替康组1年生存率为36.2%，而单纯支持治疗组为13.8%。在多变量分析中，经预后因素校正后的生存获益仍然显著（p = 0.001）。接受伊立替康治疗的患者在无体能状态恶化（p = 0.0001）、无体重减轻超过5%（p = 0.018）以及无疼痛生存（p = 0.003）方面均显著更好。在生活质量分析中，除腹泻评分外，所有显著差异均有利于伊立替康组。
我们的研究表明，尽管治疗存在副作用，但对于氟尿嘧啶治疗失败的转移性结直肠癌患者，与单纯支持治疗相比，接受伊立替康治疗时生存期更长、肿瘤相关症状更少且生活质量更好。
