Cho Hironori, Nishiike Suetaka, Yamamoto Yoshifumi, Takenaka Yukinori, Nakahara Susumu, Yasui Toshimichi, Hanamoto Atsushi, Inohara Hidenori
Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Faculty of Medicine, Suita, Osaka, Japan.
Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Faculty of Medicine, Suita, Osaka, Japan.
Auris Nasus Larynx. 2015 Oct;42(5):396-400. doi: 10.1016/j.anl.2015.02.009. Epub 2015 Feb 23.
The first-line treatment for inoperable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) has long been the combination of cisplatin and fluorouracil (PF). Recently, cetuximab has been shown to provide an additional survival benefit to PF. It remains unknown whether docetaxel adds additional benefits to PF. Therefore, we sought to evaluate the efficacy and toxicity of docetaxel, cisplatin, and fluorouracil (TPF) for inoperable recurrent or metastatic HNSCC.
A retrospective chart review from January 2005 to March 2013 identified patients who were treated with docetaxel 60 mg/m(2) on day 1, followed by cisplatin 60 mg/m(2) on day 1, and fluorouracil 600 mg/m(2)/day on days 1-5 (modified TPF) every 4 weeks for inoperable recurrent or metastatic HNSCC.
Twenty-four patients were identified; seven and five patients had locoregional disease only and distant metastasis only, respectively, while 12 patients had locoregional disease and distant metastasis simultaneously. Of the 17 patients with distant metastasis, multiple organs were affected in 9 patients, with the most frequently affected organ being the lung (n=11). Three patients had no prior treatment, whereas 21 patients underwent intensive prior treatment. In 17 of 21 patients who had received prior treatment, the treatment included chemoradiotherapy and/or chemotherapy. The median number of cycles of modified TPF was two (range, 1-5). One patient showed complete response, four patients showed partial response, two patients had stable disease, and 17 patients had progressive disease. Overall, the rate of objective response was 21%, with a 95% confidence interval (CI) of 9-40%. Median overall survival was 8.0 months (95%CI, 4.4-10.6 months). The treatment efficacy differed significantly according to extent of disease. Objective response in patients with distant metastasis alone was better than in patients with locoregional disease with or without distant metastasis (60% vs. 11%, respectively; P=0.02). Median overall survival in the former patients was longer than in the latter patients (not reached vs. 7.0 months, respectively; P=0.02). Fifteen patients (63%) had Grades 3-4 neutropenia, and seven patients (29%) developed Grade 3 febrile neutropenia. There were no toxic deaths.
The efficacy of modified TPF in the setting of first-line treatment for recurrent or metastatic HNSCC is not very high, while the toxicity is acceptable with extensive care. The development of more efficacious chemotherapeutic regimen is required.
长期以来,顺铂与氟尿嘧啶联合方案(PF)一直是不可切除的复发性或转移性头颈部鳞状细胞癌(HNSCC)的一线治疗方案。最近研究显示,西妥昔单抗可使PF方案的生存获益增加。多西他赛是否能为PF方案带来更多获益尚不清楚。因此,我们试图评估多西他赛、顺铂与氟尿嘧啶联合方案(TPF)用于不可切除的复发性或转移性HNSCC的疗效和毒性。
回顾性分析2005年1月至2013年3月期间接受治疗的患者,这些患者因不可切除的复发性或转移性HNSCC每4周接受一次改良TPF方案治疗,具体为第1天静脉滴注多西他赛60mg/m²,随后第1天静脉滴注顺铂60mg/m²,第1 - 5天静脉滴注氟尿嘧啶600mg/m²/天。
共纳入24例患者;7例患者仅存在局部区域病变,5例患者仅发生远处转移,12例患者同时存在局部区域病变和远处转移。在17例发生远处转移的患者中,9例患者多个器官受累,最常受累的器官是肺(n = 11)。3例患者未接受过先前治疗,21例患者接受过强化的先前治疗。在21例接受过先前治疗的患者中,17例患者的治疗包括放化疗和/或化疗。改良TPF方案的中位疗程数为2个周期(范围1 - 5个周期)。1例患者达到完全缓解,4例患者达到部分缓解,2例患者病情稳定,17例患者病情进展。总体而言,客观缓解率为21%,95%置信区间(CI)为9% - 40%。中位总生存期为8.0个月(95%CI,4.4 - 10.6个月)。治疗疗效根据疾病范围有显著差异。单纯远处转移患者的客观缓解率优于伴有或不伴有远处转移的局部区域病变患者(分别为60% vs. 11%;P = 0.02)。前者患者的中位总生存期长于后者患者(分别为未达到 vs. 7.0个月;P = 0.02)。15例患者(63%)发生3 - 4级中性粒细胞减少,7例患者(29%)发生3级发热性中性粒细胞减少。无治疗相关死亡。
改良TPF方案用于复发性或转移性HNSCC一线治疗的疗效不高,但其毒性在加强护理的情况下是可接受的。需要研发更有效的化疗方案。