Vasey Paul A, Jayson Gordon C, Gordon Alan, Gabra Hani, Coleman Rob, Atkinson Ronnie, Parkin David, Paul James, Hay Andrea, Kaye Stan B
Cancer Research U.K. Department of Medical Oncology, Glasgow, UK.
J Natl Cancer Inst. 2004 Nov 17;96(22):1682-91. doi: 10.1093/jnci/djh323.
Chemotherapy with a platinum agent and a taxane (paclitaxel) is considered the standard of care for treatment of ovarian carcinoma. We compared the combination of docetaxel-carboplatin with the combination of paclitaxel-carboplatin as first-line chemotherapy for stage Ic-IV epithelial ovarian or primary peritoneal cancer.
We randomly assigned 1077 patients to receive docetaxel at 75 mg/m2 of body surface area (1-hour intravenous infusion) or paclitaxel at 175 mg/m2 (3-hour intravenous infusion). Both treatments then were followed by carboplatin to an area under the plasma concentration-time curve of 5. The treatments were repeated every 3 weeks for six cycles; in responding patients, an additional three cycles of single-agent carboplatin was permitted. Survival curves were calculated by the Kaplan-Meier method, and hazard ratios were estimated with the Cox proportional hazards model. All statistical tests were two-sided.
After a median follow-up of 23 months, both groups had similar progression-free survival (medians of 15.0 months for docetaxel-carboplatin and 14.8 months for paclitaxel-carboplatin; hazard ratio [HR] docetaxel-paclitaxel = 0.97, 95% confidence interval [CI] = 0.83 to 1.13; P = .707), overall survival rates at 2 years (64.2% and 68.9%, respectively; HR = 1.13, 95% CI = 0.92 to 1.39; P = .238), and objective tumor (58.7% and 59.5%, respectively; difference between docetaxel and paclitaxel = -0.8%, 95% CI = -8.6% to 7.1%; P = .868) and CA-125 (75.8% and 76.8%, respectively; difference docetaxel-paclitaxel = -1.0%, 95% CI = -7.2% to 5.1%; P = .794) response rates. However, docetaxel-carboplatin was associated with substantially less overall and grade 2 or higher neurotoxicity than paclitaxel-carboplatin (grade > or =2 neurosensory toxicity in 11% versus 30%, difference = 19%, 95% CI = 15% to 24%; P<.001; grade > or =2 neuromotor toxicity in 3% versus 7%, difference = 4%, 95% CI = 1% to 7%; P<.001). Treatment with docetaxel-carboplatin was associated with statistically significantly more grade 3-4 neutropenia (94% versus 84%, difference = 11%, 95% CI = 7% to 14%; P<.001) and neutropenic complications than treatment with paclitaxel-carboplatin, although myelosuppression did not influence dose delivery or patient safety. Global quality of life was similar in both arms, but substantive differences in many symptom scores favored docetaxel.
Docetaxel-carboplatin appears to be similar to paclitaxel-carboplatin in terms of progression-free survival and response, although longer follow-up is required for a definitive statement on survival. Thus, docetaxel-carboplatin represents an alternative first-line chemotherapy regimen for patients with newly diagnosed ovarian cancer.
铂类药物与紫杉烷类（紫杉醇）联合化疗被认为是卵巢癌治疗的标准方案。我们比较了多西他赛 - 卡铂联合方案与紫杉醇 - 卡铂联合方案作为Ⅰc - Ⅳ期上皮性卵巢癌或原发性腹膜癌一线化疗方案的疗效。
我们将1077例患者随机分为两组，一组接受体表面积75mg/m²的多西他赛（静脉输注1小时），另一组接受175mg/m²的紫杉醇（静脉输注3小时）。两组均随后接受卡铂治疗，使血浆浓度 - 时间曲线下面积达到5。每3周重复治疗一次，共六个周期；对于有反应的患者，允许额外进行三个周期的单药卡铂治疗。采用Kaplan - Meier方法计算生存曲线，并使用Cox比例风险模型估计风险比。所有统计检验均为双侧检验。
中位随访23个月后，两组的无进展生存期相似（多西他赛 - 卡铂组为15.0个月，紫杉醇 - 卡铂组为14.8个月；多西他赛与紫杉醇的风险比[HR]=0.97，95%置信区间[CI]=0.83至1.13；P = 0.707），2年总生存率相似（分别为64.2%和68.9%；HR = 1.13，95% CI = 0.92至1.39；P = 0.238），客观肿瘤缓解率相似（分别为58.7%和59.5%；多西他赛与紫杉醇的差异=-0.8%，95% CI = -8.6%至7.1%；P = 0.868），CA - 125缓解率也相似（分别为75.8%和76.8%；多西他赛与紫杉醇的差异=-1.0%，95% CI = -7.2%至5.1%；P = 0.794）。然而，与紫杉醇 - 卡铂相比，多西他赛 - 卡铂的总体神经毒性以及2级或更高等级的神经毒性明显更低（≥2级神经感觉毒性分别为11%和30%，差异=19%，95% CI = 从15%至24%；P<0.001；≥2级神经运动毒性分别为3%和7%，差异=4%，95% CI = 1%至7%；P<0.001）。与紫杉醇 - 卡铂治疗相比，多西他赛 - 卡铂治疗的3 - 4级中性粒细胞减少症（分别为94%和84%，差异=11%，95% CI = 7%至14%；P< .001）和中性粒细胞减少并发症在统计学上显著更多，尽管骨髓抑制并未影响剂量给予或患者安全性。两组的总体生活质量相似，但在许多症状评分方面，多西他赛组有实质性优势。
在无进展生存期和缓解方面，多西他赛 -卡铂似乎与紫杉醇 - 卡铂相似，不过对于生存期做出明确结论还需要更长时间的随访。因此，多西他赛 - 卡铂是新诊断卵巢癌患者的一种一线化疗替代方案。
