The role of therapeutic drug monitoring in the management of safety of anticancer agents: a focus on 3 cytotoxics

ABSTRACT

Introduction: Therapeutic drug monitoring in oncology is used to prevent major toxicities of selected anticancer agents due to overexposure by individualizing the dose based on a pharmacokinetic target.

Areas covered: Numerous studies relating a relation between pharmacokinetic variability and toxicity have been reported since the eighties but very few have been implemented in clinical practice due to a lack of validation and harmonization, logistical constraints and reluctance from oncologists. Following recent recommendations, this paper highlights the current-validated applications of pharmacokinetic monitoring in oncology focusing on the safety of anticancer therapies.

Expert opinion: Paradoxically given the oldness of the agents, guidelines of dose adjustment have been recently available for intravenous busulfan, 5-fluorouracil, and high-dose methotrexate. Interestingly, besides the enhancement of tolerability, it applies to potential curative clinical situations. In an era of personalized oncology that integrates complex molecular factors in the treatment of cancer, education is needed for oncologists to show the benefits of this valuable (even old) resource for the safety of patients. Therapeutic drug monitoring for busulfan, 5-fluorouracil and methotrexate will still hold in the future unless more active agents are available in the concerned indications.

KEYWORDS:

• Therapeutic drug monitoring
• anticancer agent
• safety
• busulfan
• methotrexate
• 5-fluorouracil

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Article highlights

• Therapeutic drug monitoring in oncology is used to prevent major toxicities of selected anticancer agents due to overexposure by individualizing the dose based on a pharmacokinetic target.

• Currently, validated therapeutic drug monitoring applies to busulfan, 5-fluorouracil, and high-dose methotrexate.

• After decades of clinical studies, standardized pharmacokinetic targets for high-dose methotrexate, busulfan and recently 5-FU are now available and interestingly apply in potential curative situations.

• The implementation of therapeutic drug monitoring in clinical practice still relies on the acceptance by convinced oncologists and the availability of a local and rapid analytical infrastructure.

• Although therapeutic drug monitoring applies to old agents, it will still hold in the future unless more active agents are available in the concerned indications.

• Regarding recent agents, implementation of therapeutic drug monitoring has to face a lack of sufficient follow up or comprehensive description of side effects, the limited number of patients due to narrow indications, a strong competition with other agents and sometimes a rapid evolution of the treatment (absence of mature or stable standard of care).

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Additional information

Funding

This paper was not funded.