Wang Xu, Chen Xi, Zhu Jinhui, Li Sheng
College of Information Engineering, Zhejiang University of Technology, Hangzhou, China.
Department of General Surgery, Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China.
J Theor Biol. 2025 Feb 21;599:112033. doi: 10.1016/j.jtbi.2024.112033. Epub 2024 Dec 24.
Metronomic chemotherapy (MCT) is a novel chemotherapy approach characterized by a high-frequency, low-dose administration strategy. The "chemo-switch" regimen involves the sequential use of two dosing strategies: maximum tolerated dose (MTD) chemotherapy and MCT. For patients with pancreatic ductal adenocarcinoma (PDAC), selecting novel chemotherapy regimens appropriately according to their physical conditions may help address the challenges associated with MTD chemotherapy, such as excessive toxicity, prolonged tumor recovery, and suboptimal efficacy. There is currently limited research on mathematical models related to novel chemotherapy regimens and PDAC, as well as on the impact of different drug administration strategies and the sequence of chemoradiotherapy in combined treatment. To address these gaps, we propose a two-dimensional multiscale mathematical model. Initially, we model the individual effects of MTD chemotherapy, antiangiogenic therapy, and radiotherapy. Subsequently, we analyze the anti-tumor effects of various chemotherapy regimens and their underlying mechanisms. Furthermore, we assess how different drug administration regimens and the sequencing of chemotherapy and radiotherapy affect treatment outcomes. Simulation results indicate that, compared to standard MTD chemotherapy, using the MCT regimen or introducing MCT during MTD chemotherapy (chemo-switch regimen) demonstrates better anti-tumor efficacy and sustained tumor perfusion, enhancing drug accumulation within tumor regions. Combined therapy exhibits superior efficacy compared to monotherapy. Placing radiotherapy after anti-angiogenic therapy and chemotherapy suggests more effective in suppressing tumor growth and sustaining tumor perfusion. It is noteworthy that while this study focuses on PDAC treatment, its findings can be extrapolated to other fibrotic tumors, thereby facilitating similar analyses across different tumor types.
节拍化疗（MCT）是一种新型化疗方法，其特点是采用高频、低剂量给药策略。“化疗转换”方案涉及两种给药策略的序贯使用：最大耐受剂量（MTD）化疗和MCT。对于胰腺导管腺癌（PDAC）患者，根据其身体状况适当选择新型化疗方案可能有助于应对与MTD化疗相关的挑战，如毒性过大、肿瘤恢复时间延长和疗效欠佳。目前，关于新型化疗方案与PDAC相关的数学模型，以及不同给药策略和放化疗顺序在联合治疗中的影响的研究有限。为了填补这些空白，我们提出了一个二维多尺度数学模型。首先，我们对MTD化疗、抗血管生成治疗和放疗的个体效应进行建模。随后，我们分析各种化疗方案的抗肿瘤效应及其潜在机制。此外，我们评估不同的给药方案以及化疗和放疗的顺序如何影响治疗结果。模拟结果表明，与标准MTD化疗相比，使用MCT方案或在MTD化疗期间引入MCT（化疗转换方案）显示出更好的抗肿瘤疗效和持续的肿瘤灌注，增强了药物在肿瘤区域的积累。联合治疗比单一治疗表现出更好的疗效。在抗血管生成治疗和化疗后进行放疗在抑制肿瘤生长和维持肿瘤灌注方面似乎更有效。值得注意的是，虽然本研究侧重于PDAC治疗，但其发现可外推至其他纤维化肿瘤，从而便于对不同肿瘤类型进行类似分析。
