The dose-dense principle in chemotherapy

•A chemotherapeutic treatment consists of drugs delivered in periodic cycles.•Tumor cells regrow between cycles, reducing the benefits of the treatment.•Increasing the frequency of the cycles maximizes the cancer cell kill.•There exists a minimum time between cycles for a protocol to be effective.•D...

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Bibliographic Details
Published in:Journal of theoretical biology 2017-10, Vol.430, p.169-176
Main Authors: López, Álvaro G., Iarosz, Kelly C., Batista, Antonio M., Seoane, Jesús M., Viana, Ricardo L., Sanjuán, Miguel A.F.
Format: Article
Language:English
Subjects:
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Dose-Response Relationship, Drug
Drug Administration Schedule
Humans
Models, Theoretical
Pharmacokinetics
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Summary:•A chemotherapeutic treatment consists of drugs delivered in periodic cycles.•Tumor cells regrow between cycles, reducing the benefits of the treatment.•Increasing the frequency of the cycles maximizes the cancer cell kill.•There exists a minimum time between cycles for a protocol to be effective.•Dose-dense protocols can be beneficial, but present difficulties. Chemotherapy is a cancer treatment modality that uses drugs to kill tumor cells. A typical chemotherapeutic protocol consists of several drugs delivered in cycles of three weeks. We present mathematical analyses demonstrating the existence of a maximum time between cycles of chemotherapy for a protocol to be effective. A mathematical equation is derived, which relates such a maximum time with the variables that govern the kinetics of the tumor and those characterizing the chemotherapeutic treatment. Our results suggest that there are compelling arguments supporting the use of dose-dense protocols. Finally, we discuss the limitations of these protocols and suggest an alternative.
ISSN:0022-5193
1095-8541
DOI:10.1016/j.jtbi.2017.07.003