Bi Ting, Jin Feng, Wu Weili, Long Jinhua, Li Yuanyuan, Gong Xiuyun, Luo Xiuling, Li Zhuoling, He Qianyong, Qu Bo
Department of Head and Neck Oncology, Cancer Hospital of Guizhou Province Affiliated to Guiyang Medical College, Guiyang 550004, China.
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Zhonghua Zhong Liu Za Zhi. 2015 Sep;37(9):676-81.
To compare the therapeutic effects, toxic side effects and influence on the immune function in patients treated with TPF [docetaxel (DOC) + cisplatin (DDP) + 5-fluorouracil (5-Fu)] induction chronochemotherapy and conventional chemotherapy for locally advanced nasopharyngeal (NPC).
Seventy patients with locally advanced nasopharyngeal carcinoma were treated in our department at their first visit from April 2013 to December 2013. They were divided randomly into two groups: the chronochemotherapy group (38 patients) and conventional chemotherapy group (32 patients). All of the patients were treated with TPF regimen with 2 cycles of induction chemotherapy in a 21-28-days/cycle. The chronochemotherapy group: DOC: 75 mg/m2, i. v. gtt, d1 (03: 30-04: 30); DDP: 75 mg/m2, 10 am-10 pm, c.i.v, d1-d5; 5-Fu: 750 mg·m(-2)·d(-1), 10 pm-10 am, c. i.v., d1-d5, both chemotherapies were administered by intravenous infusion using an automatic electric pump. The conventional chemotherapy group: Both DOC and DDP were administered intravenously at a dose of 75 mg/m2 on d1. 5-Fu was given at a dose of 750 mg/m2 for 24 hours from d1-d5 with continuous infusion in a total of 120 hours. In this procedure, prescribing the conventional intravenous infusion, intensity modulated radiation therapy was used after the induction chemotherapy. The prescribed nasopharyngeal lesion dose (GTVnx) was 69.96 Gy/33 fractions for the T1-T2 nasopharygeal cancer, while 73.92 Gy/33 fractions nasopharynx lesion dose (GTVnx) for the T3-T4 nasopharyngeal cancer. The planning target volume (PTV) of positive lymph node (PTVnd) dose was 69.96 Gy/33 fractions. Concurrent chemoradiotherapy: cisplatin 100 mg/m2, i. v. gtt. d1-d2, and there were two cycles in total and 21 days each cycle.
Sixty-six patients were evaluable for the response assessment. There were 36 patients in the chronochemotherapy group and 30 patients in the conventional chemotherapy group. After the induction chemotherapy, no CR case was found in both of the two groups. The PR was 80.6% in the chronochemotherapy group and 50.0% in the conventional chemotherapy group (P=0.009). After concurrent chemoradiotherapy, the CR rate in the chronocheotherapy group was 45.5%, significantly higher than 20.7% in the conventional chemotherapy group (P=0.040). Secondly, the incidence rates of adverse reactions including bone marrow suppression, nausea, vomiting, diarrhea, constipation, oral mucositis, fatigue, anorexia in the chrono-chemotherapy group were significantly lower than that in the conventional group (P<0.05 for all). Finally, compared the two groups, the CD4+ /CD8+ ratio was significantly lower in the chronochemotherapy group than that in the conventional chemotherapy group (P<0.05). The lymphocytes CD19+ and CD4+/CD8+ were decreased and CD3+, CD4+, CD8+, CD16++CD56+ were increased in the chronochemotherapy group, while only CD3+ and CD8+ were increased in the conventional chemotherapy group.
Compared with the conventional chemotherapy, the chronochemotherapy may be more favorable in the treatment of NPC, with a better therapeutic effects and effectiveness than that of conventional chemotherapy after induction chemotherapy, with less side effects, and can improve the immune function in the patients.
比较TPF[多西他赛（DOC）+顺铂（DDP）+5-氟尿嘧啶（5-Fu）]时辰诱导化疗与传统化疗对局部晚期鼻咽癌（NPC）患者的治疗效果、毒副作用及免疫功能的影响。
2013年4月至2013年12月，70例初诊局部晚期鼻咽癌患者在我科接受治疗。随机分为两组：时辰化疗组（38例）和传统化疗组（32例）。所有患者均采用TPF方案进行2个周期的诱导化疗，周期为21-28天。时辰化疗组：DOC：75mg/m²，静脉滴注，d1（03:30-04:30）；DDP：75mg/m²，上午10点至晚上10点，持续静脉滴注，d1-d5；5-Fu：750mg·m⁻²·d⁻¹，晚上10点至上午10点，持续静脉滴注，d1-d5，两种化疗均采用自动电动泵静脉输注。传统化疗组：DOC和DDP均于d1静脉注射，剂量为75mg/m²。5-Fu从d1-d5以750mg/m²的剂量持续输注24小时，共120小时。在此过程中，采用常规静脉输注，诱导化疗后行调强放射治疗。T1-T2期鼻咽癌的鼻咽病变处方剂量（GTVnx）为69.96Gy/33次分割，而T3-T4期鼻咽癌的鼻咽病变剂量（GTVnx）为73.92Gy/33次分割。阳性淋巴结的计划靶体积（PTV）剂量为69.96Gy/33次分割。同步放化疗：顺铂100mg/m²，静脉滴注，d1-d2，共2个周期，每个周期21天。
66例患者可进行疗效评估。时辰化疗组36例，传统化疗组30例。诱导化疗后，两组均未发现CR病例。时辰化疗组PR为80.6%，传统化疗组为50.0%（P=0.009）。同步放化疗后，时辰化疗组CR率为45.5%，显著高于传统化疗组的20.7%（P=0.040）。其次，时辰化疗组骨髓抑制、恶心、呕吐、腹泻、便秘、口腔黏膜炎、疲劳、厌食等不良反应的发生率明显低于传统组（所有P<0.05）。最后，两组比较，时辰化疗组CD4⁺/CD8⁺比值明显低于传统化疗组（P<0.05）。时辰化疗组淋巴细胞CD19⁺和CD4⁺/CD8⁺降低，CD3⁺、CD4⁺、CD8⁺、CD16⁺⁺CD56⁺升高，而传统化疗组仅CD3⁺和CD8⁺升高。
与传统化疗相比，时辰化疗治疗鼻咽癌可能更具优势，诱导化疗后的治疗效果和有效性优于传统化疗，副作用更少，且能改善患者的免疫功能。
