Fushida Sachio, Fujimura Takashi, Oyama Katsunobu, Yagi Yasumichi, Kinoshita Jun, Ohta Tetsuo
Department of Gastroenterological Surgery, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
Anticancer Drugs. 2009 Sep;20(8):752-6. doi: 10.1097/CAD.0b013e32832ec02b.
We performed preoperative chemotherapy with combined docetaxel, cisplatin and S-1 (DCS therapy) for treatment of advanced gastric cancer with para-aortic lymph node metastases. The aim of this study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities. Furthermore, we evaluated the feasibility of DCS therapy in a preoperative setting, and also examined the pathological response. Fifteen patients received intravenous docetaxel and cisplatin (30, 35 or 40 mg/m2, each dose escalation was reciprocal) on days 1 and 15 and oral S-1 (40 mg/m2 twice daily) on days 1-14 every 4 weeks. After one cycle of chemotherapy, toxicities were evaluated and after two cycles of chemotherapy, patients who were judged to be candidates for curative resection underwent gastrectomy with D2 lymphadenectomy plus para-aortic lymph node dissection. The MTD of this combination was presumed to be at dose level 3 (docetaxel 40 mg/m2 and cisplatin 35 mg/m2). The dose-limiting toxicities were grade 4 neutropenia in one patient, grade 3 febrile neutropenia in two patients and grade 3 diarrhoea in two patients. Thirteen of the 15 patients received complete resection and there was no operation-related death. Good pathological responses were observed in 12 cases with lesions in the lymph nodes (complete response, n = 4; partial response, n = 8) and 11 patients with primary stomach lesions (complete response, n = 2; partial response, n = 9). This preoperative DCS therapy was considered feasible and provided a high pathological response rate in gastric cancer patients with para-aortic lymph node metastases.
我们采用多西他赛、顺铂和S-1联合方案(DCS方案)进行术前化疗,以治疗伴有主动脉旁淋巴结转移的进展期胃癌。本研究的目的是确定最大耐受剂量(MTD)和剂量限制性毒性。此外,我们评估了DCS方案在术前应用的可行性,并观察了病理反应。15例患者每4周在第1天和第15天接受静脉注射多西他赛和顺铂(30、35或40mg/m²,每次剂量递增相互交替),在第1 - 14天口服S-1(40mg/m²,每日2次)。化疗1周期后评估毒性,化疗2周期后,判断为可进行根治性切除的患者接受D2淋巴结清扫加主动脉旁淋巴结清扫的胃切除术。该联合方案的MTD推测为剂量水平3(多西他赛40mg/m²和顺铂35mg/m²)。剂量限制性毒性包括1例4级中性粒细胞减少、2例3级发热性中性粒细胞减少和2例3级腹泻。15例患者中有13例接受了根治性切除,无手术相关死亡。12例有淋巴结病变的患者(完全缓解4例;部分缓解8例)和11例原发性胃病变患者(完全缓解2例;部分缓解9例)观察到良好的病理反应。这种术前DCS方案被认为是可行的,并且在伴有主动脉旁淋巴结转移的胃癌患者中提供了较高的病理反应率。