Xiang Li, Zheng Yun, Ren PeiRong, Lin Sheng, Zhang JianWen, Wen QingLian, He LiJia, Shang ChangLing, Wu JingBo
Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou, China.
Front Oncol. 2022 Jul 27;12:868070. doi: 10.3389/fonc.2022.868070. eCollection 2022.
Currently, there is no optimal dose recommendation for a 120-h continuous infusion of 5-fluorouracil arterial cannulation for advanced T-stage nasopharyngeal carcinoma (NPC). Thus, the aim of this study was to determine the maximum tolerated dose (MDT), along with the efficacy, late adverse events, and 10-year survival outcome of 5-fluorouracil administered continuously for 120 h combined with cisplatin the superficial temporal artery in patients with advanced T-stage NPC.
Fifty-one patients with histologically confirmed advanced T-stage NPC were eligible for inclusion in this clinical trial. The patients received induction chemotherapy consisting of cisplatin (20 mg/m/d for 1-5 d) and 5-fluorouracil, administered continuously for 120 h at different dose gradients a superficial temporal artery. To identify the MTD of 5-fluorouracil infused arterially, we employed a 3 + 3 design during study phase I. The initial dose administered was 200 mg/m/d, which then was gradually escalated by 50 mg/m/d until the MTD was reached. Following two cycles of induction chemotherapy, current radical chemoradiotherapy commenced. We assessed the efficacy, survival, toxicity, and quality of life of patients following treatment.
The overall response (complete response + partial response) rates following induction chemotherapy in the primary mass and lymph nodes were 100% and 100%, respectively. All 51 (100%) patients achieved T-category down-staging after intra-arterial chemotherapy. The MTD was 450 mg/m/d for 120 h. No late neurological toxicities, such as brain stem injury, temporal lobe necrosis, and spinal cord injury, were observed. The 5- and 10-year overall survival (OS) rates were 78.0% and 71.7%, respectively, with a median OS of 131 months.
Continuous infusion of 5-fluorouracil combined with cisplatin the superficial temporal artery showed promising survival benefits and few toxicities in patients with advanced T-stage NPC.
目前，对于晚期T分期鼻咽癌（NPC）经颞浅动脉持续120小时灌注5-氟尿嘧啶，尚无最佳剂量推荐。因此，本研究旨在确定持续120小时给予5-氟尿嘧啶联合顺铂经颞浅动脉灌注治疗晚期T分期NPC患者的最大耐受剂量（MTD）、疗效、晚期不良事件及10年生存结局。
51例经组织学确诊的晚期T分期NPC患者符合纳入本临床试验的条件。患者接受诱导化疗，包括顺铂（20mg/m²/d，共1 - 5天）和5-氟尿嘧啶，经颞浅动脉以不同剂量梯度持续灌注120小时。为确定动脉内灌注5-氟尿嘧啶的MTD，在研究的I期采用3 + 3设计。初始给药剂量为200mg/m²/d，然后以50mg/m²/d的幅度逐渐递增，直至达到MTD。两个周期的诱导化疗后，开始进行当前的根治性放化疗。我们评估了治疗后患者的疗效、生存、毒性及生活质量。
诱导化疗后原发灶和淋巴结的总体缓解率（完全缓解 + 部分缓解）分别为100%和100%。所有51例（100%）患者经动脉化疗后T分期下降。120小时的MTD为450mg/m²/d。未观察到晚期神经毒性，如脑干损伤、颞叶坏死和脊髓损伤。5年和10年总生存率分别为78.0%和71.7%，中位总生存期为131个月。
经颞浅动脉持续灌注5-氟尿嘧啶联合顺铂治疗晚期T分期NPC患者显示出有前景的生存获益且毒性较小。
