Determining an Optimum Biological Dose of A Metronomic Chemotherapy

2021 ◽  
Vol 15 (1) ◽  
pp. 77-94
Author(s):  
Atanu Bhattacharjee ◽  
Vijay M Patil
2018 ◽  
Vol 55 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Atanu Bhattacharjee ◽  
Vijay M. Patil ◽  
Vanita Noronha ◽  
Amit Joshi ◽  
Kumar Prabhash

Summary The best effective dose of a chemotherapy is defined using the maximum tolerated dose (MTD) of toxicity. It is possible that the toxicity of a dose may increase when the dose-response curve is not monotonic. In the case of metronomic chemotherapy (MC) a 1/10th level of MC dose is considered as a targeted dose of therapy and is safer in terms of toxicity levels. The objective of this study is to develop an algorithm based on the dose response model of MC to evaluate the best effective dose based on the molecular target agent. The molecular target agent is defined as the optimal biological dose achieved by the best effective dose, as the lowest dose with the highest rate of safety and efficacy. The first proposed design is parametric and assumes a logistic dose-efficacy curve for dose determination, and the second design uses quadratic regression to identify the optimal biological dose. We conducted extensive simulation studies to investigate the operating characteristics of the proposed designs. Simulation studies provide a possible way to decide on the best effective dose of MC to be considered in further phases through the finding of the optimal biological dose. The proposed design is assumed, with the threshold value of optimum biological dose (OBD), to detect the best dose of MC. This consistent design with specific dose response models can be recommended for practice.


2019 ◽  
Vol 2019 ◽  
pp. 1-31 ◽  
Author(s):  
Cem Simsek ◽  
Ece Esin ◽  
Suayib Yalcin

Metronomic chemotherapy, continuous and dose-dense administration of chemotherapeutic drugs with lowered doses, is being evaluated for substituting, augmenting, or appending conventional maximum tolerated dose regimens, with preclinical and clinical studies for the past few decades. To date, the principle mechanisms of its action include impeding tumoral angiogenesis and modulation of hosts’ immune system, affecting directly tumor cells, their progenitors, and neighboring stromal cells. Its better toxicity profile, lower cost, and easier use are main advantages over conventional therapies. The evidence of metronomic chemotherapy for personalized medicine is growing, starting with unfit elderly patients and also for palliative treatment. The literature reviewed in this article mainly demonstrates that metronomic chemotherapy is advantageous for selected patients and for certain types of malignancies, which make it a promising therapeutic approach for filling in the gaps. More clinical studies are needed to establish a solidified role for metronomic chemotherapy with other treatment models in modern cancer management.


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