Department of Medical Oncology, Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwal 230, Rotterdam, The Netherlands.
Ann Oncol. 2011 Dec;22 Suppl 8:viii33-viii39. doi: 10.1093/annonc/mdr514.
Several studies in the past have tried to improve the prognosis of ovarian cancer by increasing the dose intensity of platinum. Only 2 out of 12 randomized studies showed survival benefit at the cost of significant long-term toxicity. Dose-dense induction therapy with combined weekly paclitaxel (at a dose of 90 mg/m(2)) and weekly carboplatin [at an area under the curve (AUC) of 4 mg·ml/min] followed by 3-weekly paclitaxel/carboplatin was very effective in platinum-resistant patients (response 58%, progression-free survival 10 months). In first-line, however, no survival benefit was found with the same dose-dense weekly paclitaxel/carboplatin regimen over standard-dosed 3-weekly paclitaxel/carboplatin in a randomized study. Very recently, the Japanese Gynecologic Oncology Group (JGOG) study no. 3016, randomizing patients in first-line between dose-dense weekly paclitaxel 80 mg/m(2) plus 3-weekly carboplatin AUC 6 and 3-weekly paclitaxel/carboplatin, showed a significant increase in progression-free survival (median 28 versus 17.2 months in the control arm; hazard ratio for progression, 0.71; 95% confidence interval, 0.58-0.88; P=0.0015). The 3-year overall survival was 72% versus 65% (P=0.03), respectively. The hematologic toxicity was substantial in both arms and substantially higher than observed with the weekly paclitaxel/carboplatin induction regimen. Many patients had treatment delays, dose reductions and stopped treatment prematurely. The JGOG 3016 study is the only dose-dense study with such a significant survival benefit. It is also the only dose-intensity study performed in Asian patients. Genotypes and phenotypes are thought to represent important determinants of drug efficacy in ovarian cancer. Therefore, confirmatory studies with this JGOG regimen together with translational research are needed in both Caucasian and Asian patients.
过去的几项研究试图通过提高铂类药物的剂量强度来改善卵巢癌的预后。只有 12 项随机研究中的 2 项显示出生存获益，但代价是显著的长期毒性。联合每周紫杉醇（剂量为 90mg/m2）和每周卡铂[曲线下面积（AUC）为 4mg·ml/min]的密集诱导化疗，随后进行 3 周紫杉醇/卡铂化疗，对铂类耐药患者非常有效（反应率为 58%，无进展生存期为 10 个月）。然而，在一线治疗中，同样剂量密集的每周紫杉醇/卡铂方案与标准剂量的 3 周紫杉醇/卡铂方案相比，在一项随机研究中并未发现生存获益。最近，日本妇科肿瘤学组（JGOG）研究 3016 号对一线患者进行了随机分组，分别接受密集每周紫杉醇 80mg/m2加 3 周卡铂 AUC 6 与 3 周紫杉醇/卡铂治疗，结果显示无进展生存期显著延长（对照组的中位无进展生存期分别为 28 个月和 17.2 个月；进展风险比为 0.71；95%置信区间为 0.58-0.88；P=0.0015）。3 年总生存率分别为 72%和 65%（P=0.03）。两组的血液学毒性都很严重，明显高于每周紫杉醇/卡铂诱导方案。许多患者出现治疗延迟、剂量减少和提前停止治疗。JGOG 3016 研究是唯一一项具有如此显著生存获益的密集剂量研究。这也是唯一一项在亚洲患者中进行的剂量强度研究。基因型和表型被认为是卵巢癌药物疗效的重要决定因素。因此，需要在白人和亚洲患者中进行这项 JGOG 方案的验证性研究和转化研究。
