Gynecologic Oncology Unit, Department of Women and Children Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
Department of Obstetrics and Gynecology, Hospital "Paolo Giaccone", Palermo, Italy.
Cancer Chemother Pharmacol. 2019 Mar;83(3):431-438. doi: 10.1007/s00280-018-3742-1. Epub 2018 Dec 1.
The role of dose-dense schedules in the neo-adjuvant treatment (NACT) of locally advanced cervical cancer (LACC) has been reported. This phase II study investigated activity of dose-dense paclitaxel/platinum before radical surgery (RS) in LACC patients.
The primary end-point was the rate of optimal pathological response (OPR: pathological complete/microscopic response). NACT (paclitaxel: 80 mg/m) and carboplatin (AUC 2) were administered for 6 weeks. Overall response rate (ORR) to NACT was assessed by the RECIST criteria. Patients amenable to surgery were triaged to RS. The null hypothesis was that the OPR rate would improve from 30.0 to 45.0% (α error: 0.05, β error: 0.2). The regimen would be considered active if > 25 OPRs were found.
36 patients were enrolled; 19 patients were stage IIB (52.8%) and 16 (44.4%) patients had pelvic lymph-node involvement at imaging. All patients completed neo-adjuvant chemotherapy; ORR was of 75.0%. RS was performed in 29 (93.5%) patients. Since the OPR was 16.1%, we evaluated the real chances to achieve the number of OPR required by the Simon design and decided to close the study. Grade 3/4 hematological toxicity occurred in 5 patients; surgical morbidity occurred in 14 patients. The 2-year PFS rate was 69.0%.
Dose-dense neo-adjuvant paclitaxel/carboplatin is feasible and safe in LACC patients; however, failure to achieve the primary end-point has to be recognized. Given the heterogeneity of the available studies, robust data from an adequately sized prospective study focused on more homogeneous series are required.
已报道过剂量密集方案在局部晚期宫颈癌（LACC）新辅助治疗（NACT）中的作用。本Ⅱ期研究调查了 LACC 患者在根治性手术（RS）前接受密集剂量紫杉醇/铂类药物的疗效。
主要终点为最佳病理缓解率（OPR：病理完全/显微镜下缓解）。6 周内给予 NACT（紫杉醇：80mg/m）和卡铂（AUC 2）。通过 RECIST 标准评估 NACT 的总缓解率（ORR）。可手术的患者进行 RS 分类。零假设为 OPR 率从 30.0%提高到 45.0%（α误差：0.05，β误差：0.2）。如果发现>25 例 OPR，则认为该方案有效。
共纳入 36 例患者；19 例为ⅡB 期（52.8%），16 例（44.4%）患者影像学检查有盆腔淋巴结受累。所有患者均完成了新辅助化疗；ORR 为 75.0%。29 例（93.5%）患者进行了 RS。由于 OPR 为 16.1%，我们评估了实现 Simon 设计所需 OPR 数量的实际机会，并决定关闭该研究。5 例患者出现 3/4 级血液学毒性；14 例患者发生手术并发症。2 年 PFS 率为 69.0%。
在 LACC 患者中，密集剂量的新辅助紫杉醇/卡铂是可行且安全的；然而，未能达到主要终点是需要被认识到的。鉴于现有研究的异质性，需要来自于聚焦于更同质系列的、充分大小的前瞻性研究的可靠数据。
