Samson Assuta Ashdod University Hospital, Radiotherapy Institute, Ashdod, Israel.
Assuta Medical Center, Radiotherapy Institute, Tel Aviv, Israel.
Int J Radiat Oncol Biol Phys. 2023 Sep 1;117(1):64-73. doi: 10.1016/j.ijrobp.2023.03.046. Epub 2023 Mar 17.
The aim of this study was to evaluate a formulation of pegylated liposomal mitomycin C lipidic prodrug (PL-MLP) in patients concomitantly undergoing external beam radiation therapy (RT).
Patients with metastatic disease or inoperable primary solid tumors requiring RT for disease control or symptom relief were treated with 2 courses of PL-MLP (1.25, 1.5, or 1.8 mg/kg) at 21-day intervals, along with 10 fractions of conventional RT or 5 stereotactic body RT fractions initiated 1 to 3 days after the first PL-MLP dose and completed within 2 weeks. Treatment safety was monitored for 6 weeks, and disease status was re-evaluated at 6-week intervals thereafter. MLP levels were analyzed 1 hour and 24 hours after each PL-MLP infusion.
Overall, 19 patients with metastatic (18) or inoperable (1) disease received combination treatment, with 18 completing the full protocol. Most patients (16) had diagnoses of advanced gastrointestinal tract cancer. One grade 4 neutropenia event possibly related to study treatment was reported; other adverse events were mild or moderate. Of the 18 evaluable patients, 16 were free of RT target lesion progression at first re-evaluation. Median survival of the entire patient population was 63.3 weeks. Serum MLP level correlated with dose increases and similar long circulating profiles were observed before and after RT.
PL-MLP up to 1.8 mg/kg in combination with RT treatment is safe, with a high rate of tumor control. Drug clearance is not affected by radiation. PL-MLP is potentially an attractive option for chemoradiation therapy that warrants further evaluation in randomized studies in the palliative and curative settings.
本研究旨在评估一种聚乙二醇化脂质体丝裂霉素 C 前药（PL-MLP）制剂在同时接受外照射放疗（RT）的患者中的疗效。
患有转移性疾病或需要 RT 进行疾病控制或缓解症状的不可手术的原发性实体肿瘤的患者，接受 2 个疗程的 PL-MLP（1.25、1.5 或 1.8 mg/kg），间隔 21 天，同时给予 10 次常规 RT 或 5 次立体定向体部 RT 剂量，在第 1 次 PL-MLP 剂量后 1 至 3 天开始，并在 2 周内完成。治疗安全性监测 6 周，此后每 6 周重新评估疾病状态。在每次 PL-MLP 输注后 1 小时和 24 小时分析 MLP 水平。
总体而言，19 名患有转移性疾病（18 例）或不可手术疾病（1 例）的患者接受了联合治疗，其中 18 例完成了完整方案。大多数患者（16 例）患有晚期胃肠道癌。报告了 1 例可能与研究治疗相关的 4 级中性粒细胞减少事件；其他不良反应为轻度或中度。在 18 例可评估患者中，有 16 例在首次重新评估时未出现 RT 靶病灶进展。整个患者群体的中位生存期为 63.3 周。血清 MLP 水平与剂量增加相关，并且在 RT 前后观察到相似的长循环特征。
PL-MLP 联合 RT 治疗剂量高达 1.8 mg/kg 是安全的，肿瘤控制率高。药物清除不受辐射影响。PL-MLP 可能是一种有吸引力的选择，用于放化疗，值得在姑息和根治性环境中进行随机研究进一步评估。
