Huang Ching-Wen, Hu Huang-Ming, Hsu Wen-Hung, Chen Chiao-Yun, Huang Ming-Yii, Chen Chou-Pin, Wei Po-Li, Shen Bor-Nian, Chang Tsung-Kun, Wang Jaw-Yuan
Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Nanomedicine (Lond). 2025 May;20(9):929-941. doi: 10.1080/17435889.2025.2487411. Epub 2025 Apr 21.
To evaluate the efficacy, recommended phase II dose (RP2D), dose-limiting toxicity (DLT), and safety profiles of PEP503 (NBTXR3) in combination with concurrent chemoradiotherapy (CCRT) in patients with locally advanced or unresectable rectal adenocarcinoma.
A single administration of intratumor injection of PEP503 (NBTXR3) (multiple punctures) was applied, followed by radiotherapy in combination with capecitabine or 5-fluorouacil (5-FU). Surgery was performed 8 to 12 weeks after completion of CCRT.
Thirty-two patients were enrolled (one dropped out before CCRT), comprising 20 in phase Ib and 12 in phase II. The disease control rate was 100% ( = 31). One (3.2%) and 19 (61.3%) patients achieved clinical complete response and partial response, respectively. Twenty-five patients underwent surgery, of whom 24 (96%) had R0 resection and 5 (20%) had pathological complete response. Most of the adverse events were grade 1/2 events.
Intratumor injection of PEP503 (NBTXR3) in patients with locally advanced or unresectable rectal adenocarcinoma is safe and effective. Addition of PEP503 (NBTXR3) to fluoropyrimidine-based neoadjuvant CCRT does not engender increased toxicity. The strong safety profile and encouraging efficacy of PEP503 (NBTXR3) in combination with neoadjuvant CCRT in locally advanced or unresectable rectal cancer warrant further examination in clinical studies.
This study was registered on ClinicalTrials.gov Identifier: NCT02465593.
评估PEP503（NBTXR3）联合同步放化疗（CCRT）治疗局部晚期或不可切除直肠腺癌患者的疗效、推荐的II期剂量（RP2D）、剂量限制性毒性（DLT）和安全性。
采用单次瘤内注射PEP503（NBTXR3）（多点穿刺），随后联合卡培他滨或5-氟尿嘧啶（5-FU）进行放疗。CCRT完成后8至12周进行手术。
共纳入32例患者（1例在CCRT前退出），其中Ib期20例，II期12例。疾病控制率为100%（n = 31）。分别有1例（3.2%）和19例（61.3%）患者达到临床完全缓解和部分缓解。25例患者接受了手术，其中24例（96%）实现R0切除，5例（20%）达到病理完全缓解。大多数不良事件为1/2级事件。
局部晚期或不可切除直肠腺癌患者瘤内注射PEP503（NBTXR3）安全有效。在基于氟嘧啶的新辅助CCRT中添加PEP503（NBTXR3）不会增加毒性。PEP503（NBTXR3）联合新辅助CCRT在局部晚期或不可切除直肠癌中的强大安全性和令人鼓舞的疗效值得在临床研究中进一步研究。
本研究已在ClinicalTrials.gov注册，标识符：NCT02465593。
