Istituto Nazionale Tumori, via Mariano Semmola, 80131 Napoli, Italy.
J Clin Oncol. 2011 Sep 20;29(27):3628-35. doi: 10.1200/JCO.2010.33.8566. Epub 2011 Aug 15.
Carboplatin/paclitaxel is the standard first-line chemotherapy for patients with advanced ovarian cancer. Multicentre Italian Trials in Ovarian Cancer-2 (MITO-2), an academic multicenter phase III trial, tested whether carboplatin/pegylated liposomal doxorubicin (PLD) was more effective than standard chemotherapy.
Chemotherapy-naive patients with stage IC to IV ovarian cancer (age ≤ 75 years; Eastern Cooperative Oncology Group performance status ≤ 2) were randomly assigned to carboplatin area under the curve (AUC) 5 plus paclitaxel 175 mg/m(2) or to carboplatin AUC 5 plus PLD 30 mg/m(2), every 3 weeks for six cycles. Primary end point was progression-free survival (PFS). With 632 events in 820 enrolled patients, the study would have 80% power to detect a 0.80 hazard ratio (HR) of PFS.
Eight hundred twenty patients were randomly assigned. Disease stages III and IV were prevalent. Occurrence of PFS events substantially slowed before obtaining the planned number. Therefore, in concert with the Independent Data Monitoring Committee, final analysis was performed with 556 events, after a median follow-up of 40 months. Median PFS times were 19.0 and 16.8 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.95; 95% CI, 0.81 to 1.13; P = .58). Median overall survival times were 61.6 and 53.2 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.89; 95% CI, 0.72 to 1.12; P = .32). Carboplatin/PLD produced a similar response rate but different toxicity (less neurotoxicity and alopecia but more hematologic adverse effects). There was no relevant difference in global quality of life after three and six cycles.
Carboplatin/PLD was not superior to carboplatin/paclitaxel, which remains the standard first-line chemotherapy for advanced ovarian cancer. However, given the observed CIs and the different toxicity, carboplatin/PLD could be considered an alternative to standard therapy.
卡铂/紫杉醇是晚期卵巢癌患者的标准一线化疗药物。多中心意大利卵巢癌试验-2（MITO-2）是一项学术性多中心 III 期试验，旨在测试卡铂/聚乙二醇脂质体多柔比星（PLD）是否比标准化疗更有效。
未经化疗的 IC 至 IV 期卵巢癌患者（年龄≤75 岁；东部合作肿瘤学组体能状态≤2）随机分配至卡铂 AUC5 联合紫杉醇 175mg/m²或卡铂 AUC5 联合 PLD 30mg/m²，每 3 周为一周期，共 6 周期。主要终点为无进展生存期（PFS）。在 820 名入组患者中，有 632 例发生进展事件，该研究有 80%的效能检测到 PFS 的风险比（HR）为 0.80。
820 名患者被随机分配。III 期和 IV 期疾病较为常见。在获得计划的事件数量之前，PFS 事件的发生速度明显减慢。因此，与独立数据监测委员会协商后，在中位随访 40 个月后，对 556 例事件进行了最终分析。卡铂/PLD 和卡铂/紫杉醇组的中位 PFS 时间分别为 19.0 和 16.8 个月（HR，0.95；95%CI，0.81 至 1.13；P=0.58）。卡铂/PLD 和卡铂/紫杉醇组的中位总生存期分别为 61.6 和 53.2 个月（HR，0.89；95%CI，0.72 至 1.12；P=0.32）。卡铂/PLD 产生了相似的缓解率，但毒性不同（神经毒性和脱发较少，但血液学不良反应较多）。在三个和六个周期后，整体生活质量没有明显差异。
卡铂/PLD 并不优于卡铂/紫杉醇，后者仍是晚期卵巢癌的标准一线化疗药物。然而，鉴于观察到的置信区间和不同的毒性，卡铂/PLD 可被视为标准治疗的替代方案。
