多西他赛、顺铂和 5-氟尿嘧啶（DCF）化疗治疗转移性或不可切除的局部复发性肛门鳞状细胞癌：法国跨学科 GERCOR 和 FFCD 小组的 II 期研究（Epitopes-HPV02 研究）。
Docetaxel, Cisplatin, and 5-fluorouracil (DCF) chemotherapy in the treatment of metastatic or unresectable locally recurrent anal squamous cell carcinoma: a phase II study of French interdisciplinary GERCOR and FFCD groups (Epitopes-HPV02 study).
机构信息
Centre Hospitalier Universitaire de Besançon, Besançon, France.
Clinical Investigational Center, CIC-1431, University Hospital of Besançon, Besançon, France.
出版信息
BMC Cancer. 2017 Aug 25;17(1):574. doi: 10.1186/s12885-017-3566-0.
BACKGROUND
The squamous cell carcinoma of the anus (SCCA) is a rare disease, but its incidence is markedly increasing. About 15% of patients are diagnosed at metastatic stage, and more than 20% with a localized disease treated by chemoradiotherapy (CRT) will recur. In advanced SCCA, cisplatin and 5-fluorouracil (CF) combination is the standard option but complete response is a rare event and the prognosis remains poor with most disease progression occurring within the first 12 months. We have previously published the potential role of the addition of docetaxel (D). Among 8 consecutive patients with advanced recurrent SCCA after CRT, the DCF regimen induced a complete response in 4 patients, including 3 pathological complete responses. Then, the Epitopes-HPV02 study was designed to confirm the interest of DCF regimen in SCCA patients.
METHODS
This multicentre phase II trial assesses the DCF regimen in advanced SCCA patients. Main eligibility criteria are: histologically proven SCCA, unresectable locally advanced recurrent or metastatic disease, Eastern Cooperative Oncology Group-performance status (ECOG-PS) <2, and being eligible for DCF. Patients receive either 6 cycles of standard DCF or 8 cycles of modified DCF depending on age (> vs. ≤ 75 years-old) and ECOG-PS (0 vs. 1). The trial was set up based on a Simon's optimal two-stage design for phase II trials, allowing an early futility interim analysis. The primary endpoint is the observed progression-free survival (PFS) rate at 12 months from the first DCF cycle. A PFS rate below 10% is considered uninteresting, while a PFS rate above 25% is expected. With a unilateral alpha error of 5% and a statistical power of 90%, 66 evaluable patients should be included. Main secondary endpoints are overall survival, PFS, response rate, safety, health-related quality of life, and the correlation of biomarkers with treatment efficacy.
DISCUSSION
Since the recommended CF regimen is based in a small retrospective analysis and generates a low rate of complete responses, the Epitopes-HPV02 study will establish a new standard in case of a positive result. Associated biomarker studies will contribute to understand the underlying mechanism of resistance and the role of immunity in SCCA.
TRIAL REGISTRATION
NCT02402842 , EudraCT: 2014-001789-81.
背景
肛门鳞状细胞癌（SCCA）是一种罕见的疾病，但发病率明显上升。约 15%的患者在转移阶段被诊断出，20%以上的局限性疾病经放化疗（CRT）治疗后会复发。在晚期 SCCA 中，顺铂和 5-氟尿嘧啶（CF）联合是标准选择，但完全缓解是罕见事件，且大多数疾病在最初 12 个月内进展，预后仍然很差。我们之前发表了加入多西紫杉醇（D）的潜在作用。在 CRT 后复发的 8 例晚期复发性 SCCA 连续患者中，DCF 方案诱导 4 例完全缓解，其中 3 例为病理完全缓解。随后，设计了 Epitopes-HPV02 研究以确认 DCF 方案在 SCCA 患者中的益处。
方法
这项多中心 II 期试验评估了晚期 SCCA 患者的 DCF 方案。主要入选标准为：组织学证实的 SCCA，不可切除的局部晚期复发性或转移性疾病，东部肿瘤协作组体能状态（ECOG-PS）<2，适合 DCF 治疗。根据年龄（> vs. ≤ 75 岁）和 ECOG-PS（0 vs. 1），患者接受 6 个周期标准 DCF 或 8 个周期改良 DCF。该试验基于 Simon 的最优两阶段设计进行，允许进行早期无效性中期分析。主要终点是从第一个 DCF 周期开始 12 个月时的观察无进展生存期（PFS）率。预期 PFS 率<10%认为无意义，而 PFS 率>25%则认为有意义。单侧α误差为 5%，统计效能为 90%，则应纳入 66 例可评估患者。主要次要终点包括总生存期、PFS、缓解率、安全性、健康相关生活质量以及生物标志物与治疗效果的相关性。
讨论
由于推荐的 CF 方案基于一项小型回顾性分析，且完全缓解率较低，因此，如果 Epitopes-HPV02 研究结果为阳性，将建立新的标准。相关生物标志物研究将有助于了解 SCCA 耐药的潜在机制和免疫作用。
试验注册
NCT02402842，EudraCT：2014-001789-81。
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