一项两臂、多中心、二期临床试验，比较了局部晚期口腔和口咽鳞癌患者在接受两周期分割 TPF 诱导化疗（先给予单药多西他赛、顺铂和氟尿嘧啶，1 周 1 次，共 1 周期，随后给予分割 TPF 2 周期）之前，接受 1 周期化学选择分割剂量多西他赛、顺铂和氟尿嘧啶（TPF）诱导化疗的疗效，术后联合放疗。（TISOC-1）。

A two-arm multicenter phase II trial of one cycle chemoselection split-dose docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy before two cycles of split TPF followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1).

机构信息

Department of Otorhinolaryngology.

Clinic for Internal Medicine II - Department of Hematology and Internal Oncology, Jena University Hospital, Jena.

出版信息

Ann Oncol. 2017 Aug 1;28(8):1917-1922. doi: 10.1093/annonc/mdx202.

DOI:10.1093/annonc/mdx202

PMID:28498880

Abstract

BACKGROUND

Induction chemotherapy (ICT) with docetaxel, cisplatin and fluorouracil (TPF) followed by radiotherapy is an effective treatment option for locally advanced head and neck cancer. This phase II study investigated the effectivity of a split-dose TPF ICT before surgery for locally advanced resectable (stage III/IVA) oral and oropharyngeal cancer.

PATIENTS AND METHODS

Patients received TPF split on two dosages on days 1 and 8 per cycle (30 mg/m2 docetaxel, 40 mg/m2 cisplatin, 2000 mg/m2 fluorouracil per week). Responders (reduction tumor volume ≥30% after first cycle) received three 3-week cycles and non-responders only one cycle before surgery and postoperative radio(chemo)therapy (RCT). The primary endpoint was progression-free survival rate after 24 months. Secondary endpoints were amongst others overall survival, histopathological response to ICT, toxicity, quality of life and swallowing function.

RESULTS

Fifty-four patients (91% stage IVA, 87% male, 72% oropharyngeal cancer, 70% responders) were eligible for a per-protocol analysis. The progression-free survival rate after 24 months was 88.5% for responders and 60.6% for non-responders (P = 0.005). The overall survival rate after 24 months was 97.3% for responders and 73.7% for non-responders (P = 0.032). The rate of histopathological complete remission of the primary tumor was higher in responders (P = 0.015). High-risk classification for postoperative RCT was lower in responders (P < 0.0001). The most common grade 3+ adverse event was neutropenia in 26% of patients during ICT and mucositis in 13% during postoperative RCT. During treatment and follow-up quality of life and swallowing function was not different between responders and non-responders.

CONCLUSION

Patients with oral and oropharyngeal cancer responding to split-dose TPF before surgery and postoperative RCT show good oncological results. The tri-modal treatment regime was well tolerated. ICT using tumor response as criterion for duration of ICT before surgery of oral and oropharyngeal cancer merits additional investigation in a phase III study.

CLINICAL TRIAL NUMBER

NCT01108042.

摘要

背景

多西他赛、顺铂和氟尿嘧啶（TPF）诱导化疗（ICT）联合放疗是局部晚期头颈部癌症的有效治疗选择。本Ⅱ期研究调查了术前局部可切除（Ⅲ/IVA 期）口腔和口咽癌的 TPF ICT 分割剂量的疗效。

患者和方法

患者每周期在第 1 天和第 8 天接受 TPF 分割剂量（每周 30mg/m2 多西他赛、40mg/m2 顺铂、2000mg/m2 氟尿嘧啶）。应答者（第一周期后肿瘤体积减少≥30%）接受三个 3 周周期，无应答者仅在手术前和术后放化疗（RCT）前接受一个周期。主要终点是 24 个月后的无进展生存率。次要终点包括无进展生存率、总生存率、ICT 病理反应、毒性、生活质量和吞咽功能等。

结果

54 例患者（91%IVA 期、87%男性、72%口咽癌、70%应答者）符合方案分析。24 个月时的无进展生存率为应答者 88.5%，无应答者 60.6%（P=0.005）。24 个月时的总生存率为应答者 97.3%，无应答者 73.7%（P=0.032）。应答者原发性肿瘤的病理完全缓解率较高（P=0.015）。术后 RCT 高危分类在应答者中较低（P<0.0001）。最常见的 3+级不良事件是 ICT 期间 26%的患者中性粒细胞减少和术后 RCT 期间 13%的粘膜炎。在治疗和随访期间，应答者和无应答者的生活质量和吞咽功能无差异。