Table 2.
Label recommendations for common nephrotoxic agents used in cancer therapy
| Drug | Tumor type(s) | Dose adjustment/recommendations |
|---|---|---|
| Chemotherapies | ||
| Abiraterone acetate120 | Castration-resistant prostate cancer | No dose adjustment required for patients with RI. No clinical experience in patients with severe RI and prostate cancer therefore caution is advised |
| Cisplatin100 | Testicular, ovarian, bladder and head and neck cancers | Adequate hydration is required before, during and after infusion for patients with RI, especially severe RI Cisplatin is contraindicated in patients with preexisting RI. Nephrotoxicity may be potentiated by aminoglycoside antibiotics |
| Cyclophosphamide101 | Hematological malignancies, Ewing’s sarcoma, neuroblastoma, ovarian, breast and small cell lung cancers | Adequate hydration is required before, during and after administration. Dose reduction of 50% is recommended for patients with GFR <10 mL/min |
| Enzalutamide99 | Castration-resistant prostate cancer | No dose adjustment required for patients with mild or moderate RI (CrCl ≥30 mL/min) Caution is advised in patients with severe RI (CrCl <30 mL/min) or end-stage renal disease |
| Ifosfamide102 | Wide range of tumor types | Adequate hydration is required during and after administration Ifosfamide is contraindicated in patients with preexisting RI Dose should be determined and adjusted for each individual, and kidney function should be closely monitored before and after treatment |
| Methotrexate103 | Wide range of tumor types | Adequate hydration is required before, during and after administration. Renal function should be closely monitored before, during and after treatment. Dose should be reduced if patients have RI (CrCl 20–50 mL/min) by 50%. Methotrexate is contraindicated in patients with severe RI (CrCl <20 mL/min) |
| Melphalan72 | Ovarian cancer and multiple myeloma | A 50% dose reduction is required for patients with moderate RI (CrCl 30–50 mL/min) who are scheduled to receive high-dose melphalan without hematopoietic stem cell rescue. Melphalan should not be used in patients with severe RI |
| Targeted agents | ||
| Axitinib121 | Advanced renal cell carcinoma | No dose adjustment is required Virtually no data are available regarding axitinib clearance in patients with CrCl <15 mL/min. Axitinib has not been studied in patients with RI |
| Bevacizumab98 | Colorectal, breast, nonsmall cell lung, renal, ovarian and cervical cancers | No trials have been conducted to investigate the pharmacokinetics of bevacizumab in patients with RI because the kidneys are not a major organ for bevacizumab metabolism or excretion. Discontinuation of drug if adverse events are indicated |
| Pazopanib107 | Renal cell carcinoma and soft tissue sarcoma | No dose adjustment is required with CrCl >30 mL/min Caution advised in patients with CrCl <30 mL/min |
| Sunitinib104 | Gastrointestinal stromal tumor, renal cell carcinoma and pancreatic neuroendocrine tumors | No starting dose adjustments required for patients with RI or end-stage renal disease on dialysis. Subsequent dose adjustments should be based on individual safety and tolerability. Discontinue treatment in patients with nephrotic syndrome |
| Nivolumab78 | Melanoma nonsmall cell lung cancer and advanced renal cell carcinoma | No dose adjustment is required for patients with mild or moderate RI Treatment should be permanently discontinued for patients with grade 4 creatinine elevation |
| Pembrolizumab79 | Melanoma | No dose adjustment is required for patients with mild or moderate RI Treatment should be permanently discontinued for patients with grade 3 or 4 nephritis |
| Bone-targeted agents | ||
| Zoledronic acid88 | Advanced malignancies with bone metastases | Contraindicated in patients with severe RI (CrCl <30 mL/min). Dose adjustment for patients with mild-to-moderate RI and treatment withheld for renal deterioration. Serum creatinine should be measured before each dose and daily supplementation with calcium 500 mg and vitamin D 400 IU |
| Antibiotics | ||
| Aminoglycosides (e.g., gentamicin105 and tobramycin106) | NA | Dose reductions according to degree of RI. Should be used with caution in patients with existing RI. Serum concentration monitoring of gentamicin recommended adjusting the frequency of dosage according to degree of renal function. Tobramycin should not be used concomitantly with dialysis |
Abbreviations: CrCl, creatinine clearance; GFR, glomerular filtration rate; IU, international units; NA, not applicable; RI, renal impairment.