Impact of Cisplatin Dosing Regimens on Mammary Tumor Growth in an Animal Model.

Archives of cancer biology and therapy Pub Date : 2020-01-01 Epub Date: 2020-06-15 DOI:10.33696/cancerbiology.1.004
James A Koziol, Theresa J Falls, Jan E Schnitzer
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Abstract

Background: We have recently introduced a modification of the seminal Simeoni model for tumor growth, the modification entailing the incorporation of delay differential equations into its formulation. We found that the modification was competitive with the Simeoni construct in modeling mammary tumor growth under cisplatin treatment in an animal model.

Methods: In our original study, we had two cohorts of animals: untreated, and treatment with bolus injection of cisplatin on day 0. We here explore how modifications in the cisplatin dosing scheme affect tumor growth in our model.

Results: We found that modest fractionation dosing schemes have little ultimate impact on tumor growth. In contrast, metronomic dosing schemes seem quite efficacious, and might yield effective control over tumor progression.

Conclusions: With regard to cisplatin as single agent chemotherapy, a minimum level of drug for a prolonged period of time seems more critical than rapid achievement of a very high dose for a shorter time frame for deterring tumor growth or progression. Exploration of tumor dose schedules with mathematical models can provide valuable insights into potentially effective therapeutic regimens.

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顺铂剂量方案对动物模型乳腺肿瘤生长的影响
背景:最近,我们对开创性的 Simeoni 肿瘤生长模型进行了修改,将延迟微分方程加入到模型中。我们发现,在动物模型中模拟顺铂治疗下的乳腺肿瘤生长时,该修正模型与 Simeoni 构建模型具有竞争性:在最初的研究中,我们有两组动物:未接受治疗的动物和在第 0 天注射顺铂的动物。我们在此探讨顺铂剂量方案的改变如何影响模型中的肿瘤生长:结果:我们发现,适度的分次给药方案对肿瘤生长的最终影响很小。与此相反,节律给药方案似乎相当有效,可以有效控制肿瘤的发展:结论:对于顺铂单药化疗而言,在较短时间内达到最低用药量似乎比在较短时间内迅速达到非常高的用药量对阻止肿瘤生长或进展更为重要。利用数学模型探索肿瘤剂量计划可为潜在的有效治疗方案提供有价值的见解。
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