一项多西他赛联合洛铂对比 TPF 方案诱导化疗后同期放化疗治疗局部晚期头颈部鳞癌的前瞻性 II 期随机研究。

A prospective phase II randomized study of docetaxel combined with lobaplatin versus TPF regimen induction chemotherapy followed by concurrent chemoradiotherapy for locally advanced head and neck squamous cell carcinoma.

机构信息

Department of Head and Neck Oncology, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China.

Guizhou University Hospital, Guiyang, China.

出版信息

J Cancer Res Clin Oncol. 2023 Dec;149(20):18081-18091. doi: 10.1007/s00432-023-05497-1. Epub 2023 Nov 20.

DOI:10.1007/s00432-023-05497-1

PMID:37985501

Abstract

PURPOSE

To compare the toxicity and clinical efficacy of TL (docetaxel + lobaplatin) induction chemotherapy combined with lobaplatin concurrent chemoradiotherapy and TPF (docetaxel + cisplatin + 5-fluorouracil) induction chemotherapy combined with cisplatin concurrent chemoradiotherapy in the treatment of locally advanced head and neck squamous cell carcinoma.

METHODS AND PATIENTS

In total, 128 patients with locally advanced head and neck cancer were prospectively enrolled between August 2016 and April 2021. They were randomly divided into trial group and control group, all using chronological dosage mode. The trial group used TL regimen induction chemotherapy combined with lobaplatin concurrent chemoradiotherapy; the control group used TPF regimen induction chemotherapy and cisplatin concurrent chemotherapy. The endpoints were adverse events and survival rates at 1, 3 and 5 years.

RESULTS

Median follow-up was 42 months (20-71 months). (1) Adverse events: During induction chemotherapy, compared with TPF group, grade 3-4 leukocytes and neutrophils, diarrhea, 1-2 hyperbilirubinemia, nausea / vomiting, oral mucositis, fatigue, anorexia, hyponatremia were significantly lower in TL group (p<0. 05): 6% vs. 35%, 14% vs. 53%, 0% vs. 6%, 15% vs. 40%, 9% vs. 56%, 0% vs. 10%, 3% vs. 13%, 2% vs. 23%, 15% vs. 74%. During chemoradiotherapy, the incidence of hyponatremia, hypokalaemia and grade 1-2 nausea was significantly lower in the TL group (p<0. 05), with 24% vs. 69%, 20% vs. 65% and 24% vs. 44%, respectively. However, more grade 3-4 thrombocytopenia were observed in the TL group (15% vs. 3%, p<0. 05). (2) There was no significant difference in the recent objective response rate (ORR) between patients with TL group and TPF group (p=0.961). (3) There was no statistical difference in 1, 3 and 5 years OS between TL group and TPF group, respectively, (71.0% vs. 67.5%, p=0.573), (56.6% vs. 56.9%, p=0.814), (52.5% vs. 52.9%, p=0.841); 1, 3 and 5 years PFS are: (63.4% vs. 64.0%, p=0.883), (51.1% vs. 54.0%, p=0.705) and (47.3% vs. 45.9%, p=0.887), None of them were significantly different. Multivariate analysis of COX regression showed that T stage (p=0.01) and surgery (p=0.046) were independent factors affecting PFS and OS, respectively. OS subgroup analysis shows that people receiving the TL regimen in postoperative and nodal stage N1 and N2 patients tended to survive longer than those receiving the TPF regimen.

CONCLUSION

Patients with postoperative, N1 or N2 stage locally advanced head and neck squamous cell carcinoma (HNSCC) may have more significant clinical benefits when treated with TL regimen. TL regimen has advantages in reducing toxic side effects and can be used as one of the first-line treatment options.

TRIAL REGISTRATION

ClinicalTrials.gov (No. NCT03117257).

摘要

目的

比较 TL（多西他赛+洛铂）诱导化疗联合洛铂同期放化疗与 TPF（多西他赛+顺铂+5-氟尿嘧啶）诱导化疗联合顺铂同期放化疗治疗局部晚期头颈部鳞状细胞癌的毒性和临床疗效。

方法和患者

本研究前瞻性纳入了 2016 年 8 月至 2021 年 4 月间的 128 例局部晚期头颈部癌患者，采用随机数字表法将患者分为试验组和对照组，均采用序贯剂量模式。试验组采用 TL 方案诱导化疗联合洛铂同期放化疗；对照组采用 TPF 方案诱导化疗和顺铂同期化疗。终点为不良事件和 1、3、5 年的生存率。

结果

中位随访时间为 42 个月（20-71 个月）。（1）不良事件：在诱导化疗期间，与 TPF 组相比，TL 组 3-4 级白细胞和中性粒细胞、腹泻、1-2 级高胆红素血症、恶心/呕吐、口腔黏膜炎、乏力、食欲减退、低钠血症发生率明显较低（p<0.05）：6%比 35%、14%比 53%、0%比 6%、15%比 40%、9%比 56%、0%比 10%、3%比 13%、2%比 23%、15%比 74%。在同期放化疗期间，TL 组低钠血症、低钾血症和 1-2 级恶心的发生率明显较低（p<0.05），分别为 24%比 69%、20%比 65%和 24%比 44%。然而，TL 组观察到更多的 3-4 级血小板减少症（15%比 3%，p<0.05）。（2）TL 组和 TPF 组患者的近期客观缓解率（ORR）无显著差异（p=0.961）。（3）TL 组和 TPF 组患者的 1、3 和 5 年 OS 分别无统计学差异，（71.0%比 67.5%，p=0.573）、（56.6%比 56.9%，p=0.814）、（52.5%比 52.9%，p=0.841）；1、3 和 5 年 PFS 为：（63.4%比 64.0%，p=0.883）、（51.1%比 54.0%，p=0.705）和（47.3%比 45.9%，p=0.887），均无显著差异。COX 回归多因素分析显示，T 分期（p=0.01）和手术（p=0.046）是影响 PFS 和 OS 的独立因素。OS 亚组分析显示，术后及淋巴结 N1 和 N2 期接受 TL 方案治疗的患者生存时间可能更长。