Personalized pharmacotherapy in oncology: Application of pharmacokinetic-pharmacodynamic criteria.

OBJECTIVE

Indication of personalized pharmacotherapy in oncologic patients is  based on the selection of the optimal treatment (drugs, dosing, routes and  methods of administration and duration) and on the most appropriate dosing  method to achieve maximum antineoplastic efficacy, expressed in terms of  remission or relapse-free time and acceptable toxicity for the patients. The aim  of this study was to explore the contribution of therapeutic monitoring of  plasma concentrations and of the application of the pharmacokinetic and  pharmacodynamic information available for some widely used drugs to  therapeutic personalization to the care of oncologic patients.

METHOD

A complete non-systematic literature review was carried out of the  pharmacokinetic and pharmacodynamic properties of antineoplastic agents, as  well as of the results of their use in clinical practice. The search for high quality  articles included primary and secondary bibliographic sources. The  benefits of therapeutic monitoring were evaluated for parenteral cytotoxic  rugs, oral antineoplastic drugs, monoclonal antibodies and other biological  therapies used in clinical practice.

RESULTS

Therapeutic personalization of antineoplastic drugs based on therapeutic monitoring of plasma concentrations together with the information provided by pharmacokinetic-pharmacodynamic models makes it  possible to reduce toxicity and increase the effectiveness of treatment. When  personalized treatment is established with high-dose methotrexate in patients  with osteosarcoma, target maximum concentrations are reached in 70% of the  cycles (49% when fixed doses are used). When 5-fluorouracil is used in  patients with colorectal cancer, the response rate is 33.7% (18.3% with fixed  doses). Similar benefit rates are obtained with asparaginase, busulfan, oral  antineoplastics and monoclonal antibodies.

CONCLUSIONS

Due to the narrow therapeutic range of antineoplastic drugs and  the highly variable clinical response they elicit, both in terms of  effectiveness and safety, the monitoring of their plasma concentrations and the  application of pharmacokinetic and pharmacodynamic principles and  models constitute feasible and promising tools in the personalization of  oncologic treatment.