Anticancer drug renal toxicity and elimination: dosing guidelines for altered renal function

The narrow therapeutic index of anticancer drugs presents a clinical dilemma when these agents are administered to patients with impaired or unstable renal function. The purpose of this review is to (i) describe the nephrotoxicity of certain anticancer drugs, (ii) evaluate the fraction of renal clearance for pertinent anticancer drugs, and (iii) make general recommendations for the dosing of these drugs in the presence of impaired renal function. Pharmacokinetic, pharmacodynamic, and clinical toxicity information was obtained from current scientific and clinical literature. Recommendations for dosage adjustment of drugs is based on their nephrotoxicity, or renal clearance equal to or exceeding 30% of the administered dose. The specific formula used to calculate dosage adjustment of renally cleared anticancer drugs is based on fundamental pharmacokinetic principles. In addition, prospectively validated formulae for the dosage adjustment of specific agents, such as carboplatin are also reviewed. Forty-eight anticancer drugs are reviewed in this report. Nephrotoxicity is associated with 12 of these agents (Table 1). Renal clearance equal to or exceeding 30% of the administered dose is a characteristic of 17 of the drugs studied (Table 2), and a general recommendation for dose adjustment of these anticancer drugs is presented in Table 3. Renal clearance that is less than 30% of the administered dose is a feature of 31 anticancer drugs (Table 4) included in this review. This report provides general guidelines to adjust doses of renally excreted or nephrotoxic anticancer drugs in patients who present with altered renal function.