不可切除胰腺癌的 MR 引导放疗联合吉西他滨/白蛋白紫杉醇化疗：TITE-CRM Ⅰ期试验。
MR-Guided Radiation Therapy With Concurrent Gemcitabine/Nab-Paclitaxel Chemotherapy in Inoperable Pancreatic Cancer: A TITE-CRM Phase I Trial.
机构信息
Washington University School of Medicine, Department of Radiation Oncology, St. Louis, Missouri.
University of Colorado School of Medicine, Department of Radiation Oncology, Denver, Colorado.
出版信息
Int J Radiat Oncol Biol Phys. 2023 Jan 1;115(1):214-223. doi: 10.1016/j.ijrobp.2022.07.015. Epub 2022 Jul 22.
PURPOSE
Ablative radiation therapy for borderline resectable or locally advanced pancreatic ductal adenocarcinoma (BR/LA-PDAC) may limit concurrent chemotherapy dosing and usually is only safely deliverable to tumors distant from gastrointestinal organs. Magnetic resonance guided radiation therapy may safely permit radiation and chemotherapy dose escalation.
METHODS AND MATERIALS
We conducted a single-arm phase I study to determine the maximum tolerated dose of ablative hypofractionated radiation with full-dose gemcitabine/nab-paclitaxel in patients with BR/LA-PDAC. Patients were treated with gemcitabine/nab-paclitaxel (1000/125 mg/m) x 1c then concurrent gemcitabine/nab-paclitaxel and radiation. Gemcitabine/nab-paclitaxel and radiation doses were escalated per time-to-event continual reassessment method from 40 to 45 Gy 25 fxs with chemotherapy (600-800/75 mg/m) to 60 to 67.5 Gy/15 fractions and concurrent gemcitabine/nab-paclitaxel (1000/100 mg/m). The primary endpoint was maximum tolerated dose of radiation as defined by 60-day dose limiting toxicity (DLT). DLT was treatment-related G5, G4 hematologic, or G3 gastrointestinal requiring hospitalization >3 days. Secondary endpoints included resection rates, local progression free survival (LPFS), distant metastasis free survival (DMFS), and overall survival (OS).
RESULTS
Thirty patients enrolled (March 2015-February 2019), with 26 evaluable patients (2 progressed before radiation, 1 was determined ineligible for radiation during planning, 1 withdrew consent). One DLT was observed. The DLT rate was 14.1% (3.3%-24.9%) with a maximum tolerated dose of gemcitabine/nab-paclitaxel (1000/100 mg/m) and 67.5 Gy/15 fractions. At a median follow-up of 40.6 months for living patients the median OS was 14.5 months (95% confidence interval [CI], 10.9-28.2 months). The median OS for patients with Eastern Collaborative Oncology Group 0 and carbohydrate antigen 19-9 <90 were 34.1 (95% CI, 13.6-54.1) and 43.0 (95% CI, 8.0-not reached) months, respectively. Two-year LPFS and DMFS were 85% (95% CI, 63%-94%) and 57% (95% CI, 34%-73%), respectively.
CONCLUSIONS
Full-dose gemcitabine/nab-paclitaxel with ablative magnetic resonance guided radiation therapy dosing is safe in patients with BR/LA-PDAC, with promising LPFS and DMFS.
目的
对于边界可切除或局部进展性胰腺导管腺癌（BR/LA-PDAC），消融性放射治疗可能会限制同时进行的化疗剂量，并且通常仅可安全用于远离胃肠道器官的肿瘤。磁共振引导的放射治疗可能安全地允许增加放射和化疗剂量。
方法和材料
我们进行了一项单臂 I 期研究，以确定 BR/LA-PDAC 患者接受消融性低分割放射治疗和全剂量吉西他滨/ nab-紫杉醇的最大耐受剂量。患者接受吉西他滨/ nab-紫杉醇（1000/125mg/m）x1c 治疗，然后同时接受吉西他滨/ nab-紫杉醇和放射治疗。根据时间事件持续重新评估方法，按吉西他滨/ nab-紫杉醇剂量逐渐增加（40 至 45Gy25fx，600-800/75mg/m）至 60 至 67.5Gy/15 次分割，并同时接受吉西他滨/ nab-紫杉醇（1000/100mg/m）。主要终点是定义为 60 天剂量限制毒性（DLT）的放射治疗最大耐受剂量。DLT 是与治疗相关的 G5、G4 血液学毒性或 G3 胃肠道毒性，需要住院治疗>3 天。次要终点包括切除率、局部无进展生存期（LPFS）、远处转移无进展生存期（DMFS）和总生存期（OS）。
结果
共有 30 名患者入组（2015 年 3 月至 2019 年 2 月），其中 26 名患者可评估（2 名患者在接受放射治疗前进展，1 名患者在计划接受放射治疗期间被确定不符合条件，1 名患者撤回同意）。观察到 1 例 DLT。DLT 率为 14.1%（3.3%-24.9%），最大耐受剂量为吉西他滨/ nab-紫杉醇（1000/100mg/m）和 67.5Gy/15 次分割。对于仍存活的患者，中位随访时间为 40.6 个月，中位 OS 为 14.5 个月（95%CI，10.9-28.2 个月）。ECOG 评分 0 分和 CA19-9<90 的患者中位 OS 分别为 34.1 个月（95%CI，13.6-54.1）和 43.0 个月（95%CI，8.0-未达到）。2 年 LPFS 和 DMFS 分别为 85%（95%CI，63%-94%）和 57%（95%CI，34%-73%）。
结论
BR/LA-PDAC 患者接受全剂量吉西他滨/ nab-紫杉醇联合消融性磁共振引导放射治疗剂量是安全的，具有良好的 LPFS 和 DMFS。
Zotero 插件