title: Evidence for therapeutic drug monitoring of targeted anticancer therapies.
abstract: Therapeutic drug monitoring (TDM) provides valuable guidance for dose adjustment of antibiotics, immunosuppressives, antiepileptics, and other drugs, but its use for traditional anticancer therapies has been limited. Perhaps the most important obstacle is the impractical requirement of multiple blood samples to adequately define systemic exposure of drugs that have a short elimination half-life and are given by intermittent intravenous injections. However, the newer targeted anticancer therapies have different pharmacokinetic (PK) and dosing characteristics compared with traditional cytotoxic drugs, making it possible to estimate the steady-state drug exposure with a single trough-level measurement. Recent evidence indicates that certain PK parameters, including trough levels, are correlated with clinical outcomes for many of these agents, including imatinib, sunitinib, rituximab, and cetuximab. Although the current evidence is insufficient to mandate TDM in routine practice, a concerted investigation should be encouraged to determine whether the steady-state trough measurements of targeted agents will have a practical place in the clinical care of patients with cancer.
authors.affiliation: Department of Medical Oncology, Westmead Hospital, Westmead 2145 NSW, Australia. howard.gurney@sydney.edu.au
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.forename: Shang
authors.initials: S
authors.lastname: Yeap
authors.forename: Arthur
authors.initials: A
authors.lastname: Clements
authors.forename: Bavanthi
authors.initials: B
authors.lastname: Balakrishnar
authors.forename: Mark
authors.initials: M
authors.lastname: Wong
authors.forename: Howard
authors.initials: H
authors.lastname: Gurney
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000097:blood; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001549:Benzamides; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000097:blood; D000068818:Cetuximab; D000069439:Dasatinib; D016903:Drug Monitoring / Q000379:methods*; D000068338:Everolimus; D019317:Evidence-Based Medicine; D006207:Half-Life; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000008:administration & dosage / Q000097:blood; D007275:Injections, Intravenous; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood; D011743:Pyrimidines / Q000008:administration & dosage / Q000097:blood; D011758:Pyrroles / Q000008:administration & dosage / Q000097:blood; D000069283:Rituximab; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood; D000077157:Sorafenib; D000077210:Sunitinib; D013844:Thiazoles / Q000008:administration & dosage / Q000097:blood
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D001549:Benzamides; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D010879:Piperazines; D011725:Pyridines; D011743:Pyrimidines; D011758:Pyrroles; D013844:Thiazoles; D009536:Niacinamide; D000069283:Rituximab; C401859:temsirolimus; D000068877:Imatinib Mesylate; D000068338:Everolimus; D000077157:Sorafenib; C498826:nilotinib; D000068818:Cetuximab; D000069439:Dasatinib; D000077210:Sunitinib; D020123:Sirolimus