The dose-dense principle in chemotherapy

• Published in: Journal of theoretical biology Vol. 430; pp. 169 - 176
• Main Authors: López, Álvaro G., Iarosz, Kelly C., Batista, Antonio M., Seoane, Jesús M., Viana, Ricardo L., Sanjuán, Miguel A.F.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 07.10.2017
• 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
• ISSN: 0022-5193; 1095-8541
• DOI: 10.1016/j.jtbi.2017.07.003

•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.