Guo Ling, Lin Huan-Xin, Xu Min, Chen Qiu-Yan, Wang Cheng-Tao, Huang Pei-Yu
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong 510060, PR China.
Chin J Cancer. 2010 Feb;29(2):136-9. doi: 10.5732/cjc.009.10367.
PF regimen is the standard chemotherapy for advanced head and neck cancers including nasopharyngeal cancer. Recently PF has been found to enhance the tumor control by addition of Taxotere. The purpose of this study was to evaluate the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of TPF neoadjuvant regimen (taxotere, cisplatin (DDP) and 5-fluorouracil (5-FU)) followed by radical radiotherapy in advanced nasopharyngeal carcinoma (NPC).
Between December 2006 and May 2008, 41 patients with newly diagnosed UICC stage III or IV advanced nasopharyngeal cancer were enrolled. There were 29 male and 12 female patients, with a median age of 47 years (range, 29-60 years), and ECOG performance status < or = 2. The initial dose was taxotere 40 mg/m(2) d1, DDP 40 mg/m(2) d1, and 5-FU 400 mg/m(2) d1-5. The treatment was repeated every 3 weeks for two cycles. Each dose of taxotere and DDP was increased by 5 mg/m(2) and 5-FU by 50 mg/m(2), respectively. The dose was escalated after six patients completed two cycles at the initial dose and DLT was assessed. Radiotherapy was started from the 5th week, with 68-72 Gy/34-36 fractions delivered to the nasopharynx and 60-66 Gy/30-33 fractions to the node-positive area.
Forty patients (79 cycles) were evaluated for toxicity and efficacy of the therapy. No DLT occurred at the dose levels 1-4. At dose level 5, three of six patients experienced DLT including grade III/IV neutropenia lasting more than 1 week. Two of them also had grade III mucositis, leading to the interruption of radiotherapy for more than 1 week. Three more new patients were retreated with the same dose (at dose level 6) under the G-CSF support, and no DLT occurred. Dose escalation continued to level 7, and DLT was found in all of the four patients, including three grade IV neutropenia, one of them had fever and pneumonitis; three grade III diarrhea; and one grade III mucositis lasting 10 days. Dose escalation was stopped and three more new patients were treated again at dose level 5 and no DLT was found. Other severe toxicities included grade III anemia (1 patients), grade III vomiting (4 patients), and grade III weight loss (9 patients). No severe hepatic and renal toxicities were found.
TPF neoadjuvant chemotherapy is a safe and effective regimen in the treatment of advanced NPC, with recommended doses of taxotere 60 mg/m(2) d1, DDP 60 mg/m(2) d1, and 5-FU 600 mg/m(2) d1-5.
PF方案是包括鼻咽癌在内的晚期头颈癌的标准化疗方案。最近发现PF方案联合多西他赛可提高肿瘤控制率。本研究旨在评估TPF新辅助方案（多西他赛、顺铂（DDP）和5-氟尿嘧啶（5-FU））序贯根治性放疗在晚期鼻咽癌（NPC）中的剂量限制性毒性（DLT）和最大耐受剂量（MTD）。
2006年12月至2008年5月，纳入41例新诊断的国际抗癌联盟（UICC）III期或IV期晚期鼻咽癌患者。其中男性29例，女性12例，中位年龄47岁（范围29 - 60岁），东部肿瘤协作组（ECOG）体能状态≤2。初始剂量为多西他赛40mg/m² d1、DDP 40mg/m² d1、5-FU 400mg/m² d1 - 5。每3周重复治疗2个周期。多西他赛和DDP的剂量分别每次增加5mg/m²，5-FU每次增加50mg/m²。6例患者按初始剂量完成2个周期后评估DLT并进行剂量递增。放疗从第5周开始，鼻咽部给予68 - 72Gy/34 - 36次分割，阳性淋巴结区域给予60 - 66Gy/30 - 33次分割。
40例患者（79个周期）接受了治疗毒性和疗效评估。在1 - 4剂量水平未发生DLT。在剂量水平5时，6例患者中有3例出现DLT，包括III/IV级中性粒细胞减少持续超过1周。其中2例还出现III级黏膜炎，导致放疗中断超过1周。另外3例新患者在粒细胞集落刺激因子（G-CSF）支持下以相同剂量（剂量水平6）重新治疗，未发生DLT。剂量递增至水平7时，4例患者均出现DLT，包括3例IV级中性粒细胞减少，其中1例伴有发热和肺炎；3例III级腹泻；1例III级黏膜炎持续10天。停止剂量递增，另外3例新患者再次按剂量水平5治疗，未发现DLT。其他严重毒性包括III级贫血（1例）、III级呕吐（4例）和III级体重减轻（9例）。未发现严重肝、肾毒性。
TPF新辅助化疗是治疗晚期NPC的一种安全有效的方案，推荐剂量为多西他赛60mg/m² d1、DDP 60mg/m² d1、5-FU 600mg/m² d1 - 5。
