Shitara Kohei, Sakata Yuh, Kudou Toshihiro, Munakata Masaki
Dept. of Medical Oncology, Misawa City Hospital, Japan.
Gan To Kagaku Ryoho. 2006 Jun;33 Suppl 1:43-51.
Two pivotal phase II studies of S-1 in advanced gastric cancer showed response rates of 44% and 49%, and the overall survival time was 207 and 250 days, respectively. The response rate of S-1 exceeded the response rates of other approved drugs, and was comparable to that of combination chemotherapies such as 5-fluorouracil (5-FU) plus cisplatin (CDDP). These data suggested that S-1 could be used as a first-line drug for gastric cancer with a great advantage in quality of life (QOL), because it is an oral drug and can be used at an outpatient clinic. The overall incidences of adverse reactions in the phase II studies were 74.3%, and that of grade 3 or worse were 14.9%. The main adverse reactions were myelosuppression and GI toxicities. As hematological toxicity was more common than other oral fluoropyrimidine derivatives such as UFT, a careful hematological monitoring is necessary. To confirm the survival benefit of S-1 in advanced gastric cancer, a phase III trial of S-1 vs 5-FU vs CDDP plus irinotecan (CPT-11) has been conducted by the Japan Clinical Oncology Group (JCOG), and these results have been awaited. Furthermore, the combination of S-1 with CDDP, CPT-11 or taxane for the treatment of gastric cancer is feasible and active, and phase III studies of S-1 vs several combination therapies including S-1 are also in progress. The effect of S-1 in adjuvant setting is also promising. Currently, a phase III study of surgery alone vs S-1 in patients with a curative resection of gastric cancer has been developed. Further therapeutic benefits are also expected by combining S-1 with other chemotherapeutic agents such as molecular targeted agents.
两项关于S-1用于晚期胃癌的关键II期研究显示，缓解率分别为44%和49%，总生存时间分别为207天和250天。S-1的缓解率超过了其他已获批药物的缓解率，与5-氟尿嘧啶（5-FU）加顺铂（CDDP）等联合化疗的缓解率相当。这些数据表明，S-1可作为胃癌的一线药物，在生活质量（QOL）方面具有很大优势，因为它是口服药物，可在门诊使用。II期研究中不良反应的总发生率为74.3%，3级及以上不良反应的发生率为14.9%。主要不良反应为骨髓抑制和胃肠道毒性。由于血液学毒性比其他口服氟嘧啶衍生物如优福定更常见，因此需要仔细进行血液学监测。为了证实S-1在晚期胃癌中的生存获益，日本临床肿瘤学会（JCOG）开展了一项S-1对比5-FU对比CDDP加伊立替康（CPT-11）的III期试验，目前正在等待结果。此外，S-1与CDDP、CPT-11或紫杉烷联合用于治疗胃癌是可行且有效的，S-1对比包括S-1在内的几种联合疗法的III期研究也在进行中。S-1在辅助治疗中的效果也很有前景。目前，已开展了一项关于胃癌根治性切除术后患者单纯手术对比S-1的III期研究。将S-1与其他化疗药物如分子靶向药物联合使用，预计还会有进一步的治疗益处。
