自20世纪60年代以来，5-氟尿嘧啶（5-Fu）一直是治疗头颈部恶性肿瘤的基础用药，目前绝大多数治疗头颈癌的规范方案（如PF、TPF）中均包含5-Fu或其衍生物。

TS-1是一种氟尿嘧啶衍生物口服抗癌剂，包括替加氟（FT）和以下2类调节剂：吉美嘧啶（CDHP）和奥替拉西（Oxo）。其3种组分的作用如下：FT是5-Fu的前体药物，具有优良的口服生物利用度，能在活体内转化为5-Fu。CDHP能够抑制在二氢嘧啶脱氢酶作用下从FT释放出的5-Fu的分解代谢，有助于长时间维持血液和肿瘤组织中5-Fu的有效浓度，从而取得与5-Fu持续静脉输注类似的疗效。Oxo能够阻断5-Fu的磷酸化，口服给药后，Oxo在胃肠组织中具有很高的分布浓度，从而影响5-Fu在胃肠道的分布，进而降低5-Fu的毒性作用。TS-1与5-Fu相比具有以下优点：①能维持较高的血药浓度并提高抗癌活性；②药物毒性明显减少；③给药方便。

在日本，TS-1于1999年被批准用于治疗晚期胃癌，2001年被批准用于治疗头颈癌，2003年被批准用于治疗结直肠癌，2004年被批准用于治疗非小细胞肺癌。多年的临床应用表明，TS-1是安全有效的抗癌药物。据统计，日本目前晚期胃癌的化疗，80％以上使用TS-1，治疗有效率（CR＋PR）达44.6%。

治疗晚期头颈癌的方案：口服120mg/d（分2次，每次60mg），连续服用4周，休息2周（也可服药2周，休息1周），完成1个疗程，必要时可长期服用，直至肿瘤完全消失。主要副作用是血液毒性，例如白细胞减少、轻度大细胞性贫血等。

TS-1简要说明

成分

呋喃脲嘧啶+5-氯-2，4-二羟吡啶，氧晴镁钾（OXO植物生长抑制素），替加氟。

作用机制

TS-1中的替加氟通过抑制胸苷酸合成酶，阻止脱氧尿苷酸转变为脱氧胸苷酸，从而干扰DNA的合成。而其中的吉莫斯特通过抑制胃肠道的氟尿嘧啶降解酶，达到延长药物作用时间的目的。TS-1中的氧嗪酸钾是胃黏膜保护剂。

适应证

胃癌、头颈肿瘤、结直肠癌、非小细胞肺癌。

用法、用量

（1）体表面积＜1.25 m2的患者，每次用40mg，每天2次。早餐和晚餐后服用。28天为一个周期，间隔14天重复。
（2）体表面积在1.25～1.5m2的患者，每次用50mg，每天2次。早餐和晚餐后服用。28天为一个周期，间隔14天重复。
（3）体表面积＞1.5 m2的患者，每次用60mg，每天2次。早餐和晚餐后服用。28天为一个周期，间隔14天重复。
（4）如果患者在服药期间肝、肾功能正常，血液化验正常，胃肠无不适，间隔时间可以缩短为7天。每次用量可以依次调高到50、60、75mg。
（5）不能与其他氟尿嘧啶类药物和抗真菌类药物联用。

不良反应

（1）骨髓抑制。 　　
（2）肝功能损伤，食欲减退，转氨酶升高。　　
（3）严重鼻腔鼻窦癌8的发生率为0.4%。 　　
（4）严重肠炎的发生率为0.2%。

包装：20mg/140片，价格16500元。药品咨询：0411-39756018，83788633。

相关资料

Adjuvant chemotherapy with TS-1 for head and neck cancer--side effect of two-week application followed by one-week rest regimen

Multimodality therapy incorporated with radiotherapy, surgery and chemotherapy are used in the treatment of head and neck cancer in order to improve the local control and survival rate. TS-1, a newly developed oral antitumor agent which could achieve the same therapeutic concentration as that of 5-FU under continuous and intravenous treatment, has been used as adjuvant therapy for carcinomas in recent years. We presented our experience applying a new regimen of TS-1 and its side effects. TS-1 has been applied for head and neck carcinomas since 2001. The oral application of TS-1 has been used in 32 cases of head and neck cancer in our department since 2003, and the agent has been applied in 22 of 32 cases as adjuvant therapy. The primary sites of malignancy included hypopharyngx (7 cases), larynx (6 cases), maxillary sinus (2 cases), oropharynx (2 cases), oral cavity (4 cases), submandibular gland (1 case) and one case in which the primary site was unknown. A regimen of four-week application followed by two-week rest had been used in 6 cases in the first part of this trial. However, a high frequency of blood toxicity was found from the third week, requiring alteration of the protocol. Thus, a new regimen of two-week application followed by one week rest was thereafter used in the other 16 cases. Blood toxicity was found in 66.7% of those cases receiving a four-week application followed by two-week rest regimen. In the 16 cases receiving the two-week application followed by one-week rest regimen, only one case showed grade 2 leucopenia while continuous application for more than eight weeks was possible in 9 cases. Mild macrocytic anemia was found in some of these cases, however none of which required any necessary interruption of the treatment. Side effects other than blood toxicity, such as edema or pigmentation of lower limbs, erythema of skin and diarrhea, were found in the other cases, requiring suspension of the treatment. But the subsequent application was possible after a break or decreasing the dosage. We concluded that the new regimen of two-week application followed by one-week rest is less likely to be interrupted by the side effects and is safer to be used outpatiently, compared with the four-week application followed by two-week rest. Gan To Kagaku Ryoho. 2006 May;33(5):617-20.

Itoi A, Takashima M, Ishimasa H, Murata H, Tomoda K.Dept. of Otolaryngology, Head and Neck Surgery, Kanazawa Medical University（金沢医科大学）