Department of GI Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
Department of GI Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
Int J Radiat Oncol Biol Phys. 2022 Nov 1;114(3):444-453. doi: 10.1016/j.ijrobp.2022.06.089. Epub 2022 Jul 18.
Effective consolidative chemoradiation (CRT) regimens are lacking. In this phase 1 trial, we evaluated the safety and efficacy of nab-paclitaxel, capecitabine, and radiation therapy after induction chemotherapy in patients with locally advanced and borderline-resectable pancreatic cancer (LAPC and BRPC). Also, we evaluated a computed tomography (CT)-based biomarker of response.
Eligible patients had pathologically confirmed pancreatic ductal adenocarcinoma, underwent computed tomography-imaging, received a diagnosis of LAPC or BRPC, and received induction chemotherapy. Standard 3 + 3 study design was used, with 3 escalating nab-paclitaxel dose levels (50, 75, and 100 mg/m) with concurrent capecitabine and RT in cohort sizes of 3 starting at the lowest dose. Dose limiting toxicity was defined as grade 3 or higher toxicity. Patients were restaged 4 to 6 weeks post-CRT completion, and surgical resection was offered to those with stable/responsive disease. We scored the tumor interface response (IR) postchemotherapy and post-CRT into type I (remained/became more defined) and type II (became less defined). Overall survival (OS) and progression-free survival (PFS) from time of CRT were estimated using Kaplan-Meier method. P ≤ .05 was considered significant.
Twenty-three patients started and finished on protocol (LAPC = 14, BRPC = 9). No grade 3 and 4 toxicities were reported in level 1 (n = 3) or level 2 (n = 3) initial groups. Two patients in the initial level 3 group developed dose limiting toxicity, establishing level 2 dose as the maximal tolerated dose. Level 2 group was expanded for additional 15 patients (for a total of 23 on trial), 5 of whom developed grade 3 toxicities. Seven patients underwent surgical resection. Median OS and PFS were 21.2 and 8.1 months, respectively. Type I IR was associated with better OS (P = .004) and PFS (P = .03) compared with type II IR.
We established the maximum tolerated dose for nab-paclitaxel in a consolidative CRT regimen for pancreatic ductal adenocarcinoma. Preliminary efficacy results warrant phase 2 trial evaluation. IR may be used for personalized treatment.
有效的巩固性放化疗（CRT）方案仍有待探索。在这项 1 期临床试验中，我们评估了纳武利尤单抗、卡培他滨联合放疗在局部晚期和边界可切除胰腺癌（LAPC 和 BRPC）患者诱导化疗后的安全性和有效性。同时，我们评估了一种基于计算机断层扫描（CT）的反应生物标志物。
符合条件的患者均经病理证实为胰腺导管腺癌，接受 CT 影像学检查，诊断为 LAPC 或 BRPC，并接受诱导化疗。采用标准的 3+3 研究设计，3 个递增的纳武利尤单抗剂量水平（50、75 和 100mg/m）联合卡培他滨和放疗，起始剂量水平为最低剂量，每组 3 例。剂量限制性毒性定义为 3 级或更高级别的毒性。CRT 完成后 4-6 周重新分期，对稳定/有反应的患者行手术切除。我们对化疗后和 CRT 后的肿瘤界面反应（IR）进行评分，分为 I 型（保持或变得更明确）和 II 型（变得不明确）。采用 Kaplan-Meier 法估计 CRT 时的总生存期（OS）和无进展生存期（PFS）。P≤0.05 为差异有统计学意义。
23 例患者按方案开始和完成治疗（LAPC=14，BRPC=9）。1 级（n=3）和 2 级（n=3）初始组均未报告 3 级和 4 级毒性。3 级组的 2 例患者发生剂量限制性毒性，确定 2 级剂量为最大耐受剂量。2 级组扩大至另外 15 例患者（共 23 例患者入组），其中 5 例发生 3 级毒性。7 例患者接受手术切除。中位 OS 和 PFS 分别为 21.2 和 8.1 个月。与 II 型 IR 相比，I 型 IR 与更好的 OS（P=0.004）和 PFS（P=0.03）相关。
我们确定了纳武利尤单抗在胰腺导管腺癌巩固性 CRT 方案中的最大耐受剂量。初步疗效结果值得进行 2 期试验评估。IR 可用于个体化治疗。
