Comella P, Massidda B, Filippelli G, Palmeri S, Natale D, Farris A, De Vita F, Buzzi F, Tafuto S, Maiorino L, Mancarella S, Leo S, Lorusso V, De Lucia L, Roselli M
Department of Medical Oncology, National Tumour Institute, Naples, Italy.
Ann Oncol. 2005 Jun;16(6):878-86. doi: 10.1093/annonc/mdi185. Epub 2005 Apr 18.
The primary end point of this phase III trial was to compare the response rate (RR) of oxaliplatin (OXA) plus levo-folinic acid (l-FA) and 5-fluorouracil (5-FU) bolus with that of irinotecan (IRI) plus l-FA and 5-FU bolus in advanced colorectal carcinoma.
Patients with measurable metastatic colorectal carcinoma were randomly allocated to receive: IRI 200 mg/m(2) on day 1, l-FA 250 mg/m(2) intravenously plus 5-FU 850 mg/m(2) on day 2 (IRIFAFU); or OXA 100 mg/m(2) on day 1, l-FA 250 mg/m(2) plus 5-FU 1050 mg/m(2) on day 2 [OXAFAFU high dose (hd)]. Cycles were given every 2 weeks. After a planned interim analysis, OXA was reduced to 85 mg/m(2) and 5-FU to 850 mg/m(2) [OXAFAFU low dose (ld)].
Two hundred and seventy-four patients (IRIFAFU, 135; OXAFAFUhd, 71; OXAFAFUld, 68) were treated. Forty-two confirmed responses were achieved with IRIFAFU, 29 with OXAFAFUhd and 32 with OXAFAFUld. The response rate with OXAFAFU [44%; 95% confidence interval (CI) 35% to 52%] was significantly higher (P=0.029) than that of IRIFAFU (31%; 95% CI 23% to 40%). Occurrence of grade > or =3 neutropenia with OXAFAFUld was similar to that for IRIFAFU (29% versus 31%), while severe diarrhoea was significantly lower (12% versus 24%). Median failure-free survival (7 versus 5.8 months; P=0.046) and overall survival of patients (18.9 versus 15.6 months; P=0.032) were significantly prolonged with OXAFAFU.
OXAFAFU was more active and less toxic than IRIFAFU, and it should be preferred in the first-line treatment of advanced colorectal cancer patients.
本III期试验的主要终点是比较奥沙利铂（OXA）联合亚叶酸钙（l-FA）和5-氟尿嘧啶（5-FU）推注与伊立替康（IRI）联合l-FA和5-FU推注在晚期结直肠癌中的缓解率（RR）。
可测量的转移性结直肠癌患者被随机分配接受：第1天静脉注射IRI 200 mg/m²，第2天静脉注射l-FA 250 mg/m²加5-FU 850 mg/m²（IRIFAFU）；或第1天静脉注射OXA 100 mg/m²，第2天静脉注射l-FA 250 mg/m²加5-FU 1050 mg/m²[奥沙利铂联合亚叶酸钙和5-氟尿嘧啶高剂量组（hd）]。每2周进行一个周期治疗。在计划的中期分析后，奥沙利铂剂量降至85 mg/m²，5-氟尿嘧啶剂量降至850 mg/m²[奥沙利铂联合亚叶酸钙和5-氟尿嘧啶低剂量组（ld）]。
共治疗274例患者（IRIFAFU组135例；奥沙利铂联合亚叶酸钙和5-氟尿嘧啶高剂量组71例；奥沙利铂联合亚叶酸钙和5-氟尿嘧啶低剂量组68例）。IRIFAFU组有42例确诊缓解，奥沙利铂联合亚叶酸钙和5-氟尿嘧啶高剂量组有29例，奥沙利铂联合亚叶酸钙和5-氟尿嘧啶低剂量组有32例。奥沙利铂联合亚叶酸钙和5-氟尿嘧啶组的缓解率[44%；95%置信区间（CI）35%至52%]显著高于（P = 0.029）IRIFAFU组（31%；95%CI 23%至40%）。奥沙利铂联合亚叶酸钙和5-氟尿嘧啶低剂量组3级及以上中性粒细胞减少的发生率与IRIFAFU组相似（29%对31%），而严重腹泻发生率显著较低（12%对24%）。奥沙利铂联合亚叶酸钙和5-氟尿嘧啶组患者的无进展生存期（7个月对5.8个月；P = 0.046）和总生存期（18.9个月对15.6个月；P = 0.032）显著延长。
奥沙利铂联合亚叶酸钙和5-氟尿嘧啶比IRIFAFU更有效且毒性更低，应优先用于晚期结直肠癌患者的一线治疗。
