Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Cancer Chemother Pharmacol. 2018 May;81(5):815-821. doi: 10.1007/s00280-018-3554-3. Epub 2018 Mar 3.
For unresectable locally advanced (UR-LA) pancreatic cancer, chemoradiotherapy has been recommended by the NCCN guidelines. We designed a chemoradiotherapy protocol using nab-paclitaxel combined with gemcitabine (GnP) for patients with UR-LA pancreatic cancer. The purpose of this phase I study was to determine a recommended dose (RD) for this novel regimen.
Patients with UR-LA pancreatic cancer were eligible. The frequency of dose-limiting toxicities (DLTs) was evaluated, and the RD was determined. Patients were classified according to the designated dose levels of chemoradiotherapy using the GnP regimen. After additional 6 cycles of the GnP regimen were administered, surgery was considered if the patients had stable disease and tumor marker levels had normalized.
DLT (grade 4 thrombocytopenia) was observed only in 1 of 12 patients, and the RD was set at level 3. Grade 3-4 leukopenia was observed in 9 (75.0%) patients, and neutropenia in 7 (58.3%). The response rate was 41.7%, and the disease control rate was 100%. Conversion surgery was performed in 6 (50%) patients, and curative resection (R0) was performed in all 6 patients (100%). Stratification according to the Evans classification system demonstrated one patient with grade 1b, one with grade 2, two with grade 3, and two with grade 4 disease.
The RD for weekly administration was 800 mg/m for gemcitabine and 100 mg/m for nab-paclitaxel with a 50.4 Gy radiation. The GnP regimen at this dosage was promising with 6 of 12 patients proceeding to conversion surgery, and should be evaluated further in a phase II trial.
对于不可切除的局部晚期（UR-LA）胰腺癌，NCCN 指南推荐采用放化疗。我们设计了一种使用nab-紫杉醇联合吉西他滨（GnP）的放化疗方案，用于治疗 UR-LA 胰腺癌患者。本研究的目的是确定该新方案的推荐剂量（RD）。
UR-LA 胰腺癌患者符合入组条件。评估剂量限制性毒性（DLT）的频率，并确定 RD。根据 GnP 方案的指定放化疗剂量水平，将患者进行分类。如果患者病情稳定且肿瘤标志物水平正常，可考虑在完成 GnP 方案的另外 6 个周期后进行手术。
仅 12 例患者中有 1 例发生 DLT（4 级血小板减少症），RD 定为 3 级。9 例（75.0%）患者出现 3-4 级白细胞减少症，7 例（58.3%）出现中性粒细胞减少症。总缓解率为 41.7%，疾病控制率为 100%。6 例（50%）患者进行了转化手术，所有 6 例（100%）均进行了根治性切除（R0）。根据 Evans 分类系统进行分层，1 例为 1b 级，1 例为 2 级，2 例为 3 级，2 例为 4 级。
吉西他滨每周 800mg/m2和 nab-紫杉醇每周 100mg/m2联合 50.4Gy 放疗的 RD 为 50.4Gy。在该剂量下，GnP 方案有 6 例患者进行了转化手术，具有良好的应用前景，应在 II 期临床试验中进一步评估。
