Tajima Hidehiro, Makino Isamu, Gabata Ryosuke, Okazaki Mitsuyoshi, Ohbatake Yoshinao, Shimbashi Hiroyuki, Nakanuma Shinich, Saitoh Hiroto, Shimada Mari, Yamaguchi Takahisa, Okamoto Koichi, Moriyama Hideki, Kinoshita Jun, Nakamura Keishi, Miyashita Tomoharu, Ninomiya Itasu, Fushida Sachio, Ikeda Hiroko, Ohta Tetsuo
Department of Hepato-Biliary-Pancreatic Surgery, Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
Mol Clin Oncol. 2021 Feb;14(2):26. doi: 10.3892/mco.2020.2188. Epub 2020 Dec 14.
Neoadjuvant chemotherapy (NAC) has become a standard treatment for borderline resectable pancreatic ductal adenocarcinoma (PDAC). The present study examined the maximum tolerated dose of NAC with gemcitabine plus -paclitaxel (GnP) in patients with resectable PDAC. Between 2015 and 2019, 39 patients with resectable PDAC were enrolled in the present study. GnP was administered for two 28-day cycles on days 1, 8 and 15. The planned doses for levels 1, 2 and 3 were 75, 100 and 125 mg/m, respectively, for -paclitaxel and 600, 800 and 1,000 mg/m, respectively, for gemcitabine. Dose-limiting toxicity (neutropenia, anemia, thrombocytopenia and/or liver injury) was observed in 44.4% of patients treated at dose level 1 (21 patients) and 60.0% of those treated at dose level 2 (18 patients). Therefore, the maximum tolerated dose was set as level 1. Six patients withdrew from protocol treatment because of non-hematologic adverse events (skin rash, pancreatitis and biliary tract infection). Among the 31 patients with pathologically confirmed PDAC, partial response, stable disease and disease progression were recorded in 4 (12.9%), 24 (77.4%) and 3 (9.7%) patients, respectively. NAC significantly reduced tumor size according to computed tomography, and CA19-9 levels and the F-fluorodeoxyglucose maximum standardized uptake value were decreased in positron emission tomography. No postoperative complications attributable to NAC were recognized. Among the 27 patients with PDAC who underwent resection, the pathological treatment effect was judged as grades Ia, Ib and II in 21 (77.8%), 4 (14.8%) and 2 (7.4%) patients, respectively. R0 resection was performed in 24 out of 27 patients (88.9%). Adjuvant chemotherapy with oral S-1 was administered to 21 out of 27 patients (77.8%). In conclusion, NAC with GnP was safe and feasible for resectable PDAC at dose level 1. In the future, verification of the long-term results of the present study will be necessary, and a phase II clinical trial is anticipated.
新辅助化疗（NAC）已成为可切除边缘性胰腺导管腺癌（PDAC）的标准治疗方法。本研究探讨了吉西他滨联合紫杉醇（GnP）用于可切除PDAC患者时NAC的最大耐受剂量。2015年至2019年，本研究纳入了39例可切除PDAC患者。GnP在第1、8和15天给药，每28天为一个周期，共两个周期。第1、2和3剂量水平的紫杉醇计划剂量分别为75、100和125mg/m²，吉西他滨的计划剂量分别为600、800和1000mg/m²。在剂量水平1治疗的患者中有44.4%（21例）、剂量水平2治疗的患者中有60.0%（18例）观察到剂量限制性毒性（中性粒细胞减少、贫血、血小板减少和/或肝损伤）。因此，最大耐受剂量设定为剂量水平1。6例患者因非血液学不良事件（皮疹、胰腺炎和胆道感染）退出方案治疗。在31例病理确诊为PDAC的患者中，分别有4例（12.9%）、24例（77.4%）和3例（9.7%）记录为部分缓解、疾病稳定和疾病进展。根据计算机断层扫描，NAC显著缩小了肿瘤大小，正电子发射断层扫描显示CA19-9水平和氟脱氧葡萄糖最大标准化摄取值降低。未发现与NAC相关的术后并发症。在27例接受手术切除的PDAC患者中，病理治疗效果分别判定为Ia级、Ib级和II级的患者有21例（77.8%）、4例（14.8%）和2例（7.4%）。27例患者中有24例（88.9%）进行了R0切除。27例患者中有21例（77.8%）接受了口服S-1辅助化疗。总之，剂量水平1的GnP方案NAC对可切除PDAC是安全可行的。未来，有必要验证本研究的长期结果，并期待开展一项II期临床试验。
