A Systematic Review of Limited Sampling Strategies for Platinum Agents Used in Cancer Chemotherapy

Despite evidence in the literature suggesting that a strong correlation exists between the pharmacokinetic parameters and pharmacodynamic effect of anticancer agents, many of these agents are still dosed by body surface area. Therapeutic drug monitoring with the aim of pharmacokinetic-guided dosing would not only maintain target concentrations associated with efficacy but may potentially minimise the likelihood of dose-related systemic toxicities. The pharmacokinetic parameter that displays the best correlation with the pharmacodynamics of anticancer drugs is the area under the plasma concentration-time curve (AUC). However, accurate determination of the AUC requires numerous blood samples over an extended interval, which is not feasible in clinical practice. Therefore, limited sampling strategies (LSSs) have been proposed as a means to accurately and precisely estimate pharmacokinetic parameters with a minimal number of blood samples. LSSs have been developed for many drugs, particularly ciclosporin and other immunosuppressants, as well as for certain anticancer drugs. This systematic review evaluates LSSs developed for the platinum compounds and categorises 18 pertinent citations according to criteria adapted from the US Preventive Services Task Force. Thirteen citations (four level I, six level II-1, three level II-2) pertained to LSSs for carboplatin, four citations (one level II-1, one level II-2, two level III) to cisplatin LSSs, and one citation (level II-2) to nedaplatin. Based on the current evidence, it appears that LSSs may be useful for pharmacokinetic-guided dosage adjustments of carboplatin in both adults and children with cancer. Although some validation studies suggest that LSSs can be extended to different cancer populations or different chemotherapy regimens, other studies dispute this finding. Although the use of LSSs to predict the pharmacokinetic parameters of cisplatin and nedaplatin appear promising, the quality of evidence from published studies does not support routine implementation at this time. LSSs represent one approach in which clinicians can make specific dosage adjustments for individual patients to optimise outcomes. However, the limitations of these strategies must also be taken into consideration. There is also a need for prospective studies to demonstrate that application of LSSs for platinum agents ultimately improves patient response and decreases systemic toxicities.