A PHASE I DUAL DOSE ESCALATION STUDY OF RADIATION AND NAB-PACLITAXEL IN PATIENTS WITH UNRESECTABLE AND BORDERLINE RESECTABLE PANCREATIC CANCER

IF 5.3 1区医学 Q1 ONCOLOGY

Radiotherapy and Oncology Pub Date : 2025-09-01 DOI:10.1016/S0167-8140(25)04683-3

Uri Amit , John Plastaras , Rohi Gheewala , James Metz , Ursina Teitelbaum , Nevena Damjanov , Charles Schneider , Major Kenneth Lee , Mark O’Hara , Kim Reiss-Binder , Erica Carpenter , Thomas Karasic , Andre Konski , Paul Wileyto , Edgar Ben-Josef

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Abstract

Purpose:

This Phase I dual dose-escalation study aimed to evaluate the safety, feasibility, and toxicity profile of combining dose-escalated radiation therapy with high-dose nab-paclitaxel in patients with unresectable or borderline resectable pancreatic cancer. The primary objective was to determine the maximum tolerated radiation dose for the combination.

Materials and Methods:

Twenty-one evaluable patients were enrolled and allocated three radiation dose levels, 55 Gy, 57.5 Gy, and 60 Gy, administered over five weeks in 25 fractions. Concurrent nab-paclitaxel was given weekly at a dose of 125 mg/m². Radiation dose escalation was guided by a time-to-event continual reassessment method. Toxicities were monitored and classified according to CTCAE v4.0, with dose-limiting toxicities (DLT) defined as Grade 3 or higher gastrointestinal events or substantial decline in performance status. Surgical resection was pursued in patients achieving sufficient tumour downstaging.

Results:

Hematologic toxicities were the most common Grade ≥3 adverse events occurring in 76.2% of patients. Non-hematologic toxicities were less frequent (57.1%). Two Grade 3 gastrointestinal DLT cases occurred at dose levels 57.5 Gy and 60 Gy. The maximum tolerated dose was determined to be 60 Gy with a probability of DLT of 0.155 at this dose. Surgical resection with negative margins (R0) was achieved in 33.3% of patients, including all borderline resectable cases and 22.2% of initially unresectable cases. The median overall survival and time to local progression from the start of radiation therapy were 22.3 months and 20.3 months, respectively.

Conclusions:

This study demonstrates the feasibility and safety of combining dose-escalated radiation with high-dose nab-paclitaxel in locally advanced pancreatic cancer. The regimen is associated with manageable toxicity and promising local control and survival. These findings support further evaluation in larger trials to assess its impact on clinical outcomes.

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放疗和nab -紫杉醇在不可切除和边缘可切除胰腺癌患者中的I期双剂量递增研究

目的：本I期双剂量递增研究旨在评估剂量递增放射治疗联合高剂量nab-紫杉醇治疗不可切除或边缘可切除胰腺癌患者的安全性、可行性和毒性。主要目的是确定该组合的最大耐受辐射剂量。材料和方法：21名可评估的患者被纳入研究，并被分配3种辐射剂量水平，55 Gy， 57.5 Gy和60 Gy，在5周内分25次给予。同时给予nab-紫杉醇每周125 mg/m2的剂量。辐射剂量递增由事件时间连续重新评估方法指导。根据CTCAE v4.0对毒性进行监测和分类，剂量限制性毒性（DLT）定义为3级或更高的胃肠道事件或性能状态大幅下降。手术切除的患者达到足够的肿瘤降低分期。结果：血液学毒性是最常见的≥3级不良事件，发生率为76.2%。非血液学毒性较少见（57.1%）。两例3级胃肠道DLT病例发生在剂量水平57.5 Gy和60 Gy。最大耐受剂量确定为60 Gy，在该剂量下DLT的概率为0.155。33.3%的患者实现了阴性切缘（R0）手术切除，包括所有边缘可切除病例和22.2%最初不可切除病例。中位总生存期和从放疗开始到局部进展的时间分别为22.3个月和20.3个月。结论：本研究证明了剂量递增放疗联合高剂量nab-紫杉醇治疗局部晚期胰腺癌的可行性和安全性。该方案具有可控的毒性和有希望的局部控制和生存。这些发现支持在更大规模的试验中进一步评估其对临床结果的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Radiotherapy and Oncology 医学-核医学

CiteScore

10.30

自引率

10.50%

发文量

2445

审稿时长

45 days

期刊介绍： Radiotherapy and Oncology publishes papers describing original research as well as review articles. It covers areas of interest relating to radiation oncology. This includes: clinical radiotherapy, combined modality treatment, translational studies, epidemiological outcomes, imaging, dosimetry, and radiation therapy planning, experimental work in radiobiology, chemobiology, hyperthermia and tumour biology, as well as data science in radiation oncology and physics aspects relevant to oncology.Papers on more general aspects of interest to the radiation oncologist including chemotherapy, surgery and immunology are also published.