Bruce Justine Yang, Burr Adam, Kimple Randall J, Adam David P, Yu Menggang, Piaskowski Shari M, Glazer Tiffany A, Hill Patrick, Hartig Gregory K, McCulloch Timothy M, Wieland Aaron M, Trask Diana, Oliver Kate, Longcor Jarrod, Rogus-Pulia Nicole, Cho Steve Y, Bednarz Bryan, Harari Paul M
Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin (UW) School of Medicine and Public Health, Madison, WI, USA.
Department of Human Oncology, UW School of Medicine and Public Health, Madison, WI, USA.
EBioMedicine. 2025 Jan;111:105496. doi: 10.1016/j.ebiom.2024.105496. Epub 2024 Dec 12.
Re-irradiation of recurrent head and neck cancer (HNC) is often limited by tumour adherence to critical structures and/or radiation tolerance of critical normal tissues. Iopofosine I 131 (CLR 131) is a targeted small molecular phospholipid ether (PLE) drug conjugate that delivers iodine-131 selectively to tumour cells. We conducted a phase 1, single-centre, open-label study to determine whether CLR 131 given with reduced dose of external beam radiation therapy (EBRT) would be tolerable and feasible.
All participants received previous curative intent treatment with radiotherapy as primary or adjuvant treatment. Eligible participants demonstrated uptake of CLR 131 as indicated via single photon emission CT/CT (SPECT/CT) imaging following CLR 131 test dose. Participants received two therapeutic doses of CLR 131 (days 1 and 8) with SPECT/CT imaging performed to quantitate the biodistribution of CLR 131. Participants subsequently received EBRT to achieve the designated radiation dose (60-70 Gy). The primary endpoint was safety. This trial was registered with ClinicalTrials.gov, NCT04105543, and enrolment and follow-up are complete.
Twelve participants completed treatment with CLR 131 and EBRT. Eight participants experienced grade 4 non-DLT haematologic toxicities (2 anaemia, 8 leukopenia, 5 thrombocytopenia) at least probably attributed to CLR 131, consistent with the expected toxicity profile. Haematologic toxicities occurred during weeks 6-8 from the first dose of CLR 131 and resolved within three weeks without sequelae. There were no treatment-related grade 3-4 non-haematologic toxicities.
CLR 131 in combination with EBRT did not confer any safety concerns, and was tolerable in participants with recurrent/metastatic HNC. Myelosuppression was consistent with the known toxicity profile of CLR 131.
National Institutes of HealthP50 DE026787, National Cancer InstituteP30 CA014520, National Institutes of Health1UL1TR002373, Cellectar, NCT04105543.
复发性头颈癌（HNC）的再照射通常受到肿瘤与关键结构的粘连和/或关键正常组织的放射耐受性的限制。碘磷砜I 131（CLR 131）是一种靶向小分子磷脂醚（PLE）药物偶联物，可将碘-131选择性地递送至肿瘤细胞。我们进行了一项1期、单中心、开放标签研究，以确定CLR 131与降低剂量的外照射放疗（EBRT）联合使用是否可耐受且可行。
所有参与者之前均接受过以放疗作为主要或辅助治疗的根治性治疗。符合条件的参与者在CLR 131试验剂量后通过单光子发射CT/CT（SPECT/CT）成像显示CLR 131摄取。参与者接受两剂CLR 131治疗（第1天和第8天），并进行SPECT/CT成像以定量CLR 131的生物分布。参与者随后接受EBRT以达到指定的放射剂量（60 - 70 Gy）。主要终点是安全性。该试验已在ClinicalTrials.gov注册，注册号为NCT04105543，入组和随访均已完成。
12名参与者完成了CLR 131和EBRT治疗。8名参与者经历了至少可能归因于CLR 131的4级非剂量限制毒性血液学毒性（2例贫血、8例白细胞减少、5例血小板减少），与预期的毒性特征一致。血液学毒性在首次给予CLR 131后的第6 - 8周出现，并在三周内消退，无后遗症。没有与治疗相关的3 - 4级非血液学毒性。
CLR 131与EBRT联合使用不存在任何安全问题，在复发性/转移性HNC参与者中是可耐受的。骨髓抑制与CLR 131已知的毒性特征一致。
美国国立卫生研究院P50 DE026787、美国国立癌症研究所P30 CA014520、美国国立卫生研究院1UL1TR002373、Cellectar、NCT04105543。
