Saek Toshiaki, Takashima Shigemitsu, Sano Muneaki, Horikoshi Noboru, Miura Shigeto, Shimizu Satoru, Morimoto Ken, Kimura Morihiko, Aoyama Hideaki, Ota Jun, Noguchi Shinzaburo, Taguchi Tetsuo
Department of Clinical Research and Surgery, National Shikoku Cancer Center Hospital, Horinouchi 13, Matsuyama 790-0007, Japan.
Breast Cancer. 2004;11(2):194-202. doi: 10.1007/BF02968301.
S-1 is a newly developed novel oral dihydrouracil dehydrogenase inhibiting fluoropyrimidine drug consisting of 1 M tegafur (FT), 0.4 M 5-chloro-2, 4-dihydroxypyrimidine (gimeracil), and 1 M potassium oxonate (oteracil), with efficient antitumor activity and low gastrointestinal toxicity which is widely used in Japan against advanced gastric, head and neck cancers. We investigated its clinical efficacy against metastatic breast cancer.
A non-blind phase II study was carried out to evaluate the efficacy and toxicity in metastatic breast cancer patients. Patients with measurable metastasis foci (n=111) were enrolled, and 108 patients were regarded as eligible. S-1 was administered orally at a standard dose of 80 mg/m2/day b.i.d. One course consisted of 28 consecutive days of administration followed by a 14-day rest, and courses were repeated up to six times.
Among the eligible patients, 10 had a complete response and 35 had a partial response, with an overall response rate (CR+PR) of 41.7% (95% confidence interval: CI, 32.3-51.5%). The incidences of toxicity (> or =grade 3) were neutropenia 9.1%, anemia 0.9%, anorexia 3.6%, stomatitis 1.8%, nausea/vomiting 1.8%, diarrhea 0.9%, and fatigue 2.7%, however no treatment-related deaths were observed. The median survival time was 872 days (95% CI, 572-1,110 days). There was no difference in response rate or toxicity between the under 65-year-old group and the older group.
S-1 was demonstrated to have high efficacy with low gastrointestinal toxicity even in older patients and will be a promising new chemotherapy drug for metastatic breast cancer.
S-1是一种新开发的新型口服二氢嘧啶脱氢酶抑制性氟嘧啶药物，由1 M替加氟（FT）、0.4 M 5-氯-2,4-二羟基嘧啶（吉美嘧啶）和1 M奥替拉西钾组成，具有高效抗肿瘤活性和低胃肠道毒性，在日本广泛用于治疗晚期胃癌、头颈癌。我们研究了其对转移性乳腺癌的临床疗效。
开展一项非盲II期研究，以评估转移性乳腺癌患者的疗效和毒性。纳入有可测量转移灶的患者（n = 111），108例患者被视为符合条件。S-1按标准剂量80 mg/m²/天，每日两次口服给药。一个疗程包括连续28天给药，随后休息14天，疗程重复最多6次。
在符合条件的患者中，10例完全缓解，35例部分缓解，总缓解率（CR + PR）为41.7%（95%置信区间：CI，32.3 - 51.5%）。毒性（≥3级）发生率为中性粒细胞减少9.1%、贫血0.9%、厌食3.6%、口腔炎1.8%、恶心/呕吐1.8%、腹泻0.9%、疲劳2.7%，然而未观察到与治疗相关的死亡。中位生存时间为872天（95% CI，572 - 1110天）。65岁以下组和老年组在缓解率或毒性方面无差异。
S-1被证明即使在老年患者中也具有高效且胃肠道毒性低的特点，将成为转移性乳腺癌一种有前景的新型化疗药物。
