Cancer Drug Dosing in Chronic Kidney Disease and Dialysis

  • Anushree C. Shirali
    Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut, USA
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  • Ben Sprangers
    Address correspondence to Ben Sprangers, MD, PhD, MPH, MBA, Herestraat 49, b-3000 Leuven, Belgium.
    Department of Microbiology, Immunology and Transplantation, Laboratory of Molecular Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium

    Division of Nephrology, University Hospitals Leuven, Leuven, Belgium
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      Patients with malignancies have a high prevalence of kidney disease and are often treated with antineoplastic agents that undergo kidney metabolism or excretion or clearance via renal replacement therapies. Thus, the dosing of these agents, including classic chemotherapeutic drugs, targeted therapies, and immunotherapy, must take into account patients’ kidney function. In this review, we will discuss the pitfalls of accurate measurement of kidney function and how kidney disease affects both pharmacodynamic and pharmacokinetic properties of drugs. Lastly, we will discuss specific agents and summarize current dosing strategies for use in patients with chronic kidney disease and end-stage kidney disease.

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        • Launay-Vacher V.
        • Oudard S.
        • Janus N.
        • et al.
        Prevalence of Renal Insufficiency in cancer patients and implications for anticancer drug management: the renal insufficiency and anticancer medications (IRMA) study.
        Cancer. 2007; 110: 1376-1384
        • Launay-Vacher V.
        • Spano J.P.
        • Janus N.
        • et al.
        Renal insufficiency and anticancer drugs in elderly cancer patients: a subgroup analysis of the IRMA study.
        Crit Rev Oncol Hematol. 2009; 70: 124-133
        • Lichtman S.M.
        • Wildiers H.
        • Launay-Vacher V.
        • et al.
        International Society of Geriatric Oncology (SIOG) recommendations for the adjustment of dosing in elderly cancer patients with renal insufficiency.
        Eur J Cancer. 2007; 43: 14-34
        • Launay-Vacher V.
        • Aapro M.
        • De Jr., C.G.
        • et al.
        Renal effects of molecular targeted therapies in oncology: a review by the Cancer and the Kidney International Network (C-KIN).
        Ann Oncol. 2015; 26: 1677-1684
        • Kitchlu A.
        • Shapiro J.
        • Amir E.
        • et al.
        Representation of patients with chronic kidney disease in trials of cancer therapy.
        JAMA. 2018; 319: 2437-2439
        • Zhang Y.
        • Zhang L.
        • Abraham S.
        • et al.
        Assessment of the impact of renal impairment on systemic exposure of new molecular entities: evaluation of recent new drug applications.
        Clin Pharmacol Ther. 2009; 85: 305-311
        • Sprangers B.
        • Jhaveri K.D.
        • Perazella M.A.
        Improving cancer care for patients with chronic kidney disease.
        J Clin Oncol. 2020; 38: 188-192
        • Chen Y.
        • Zelnick L.R.
        • Hoofnagle A.N.
        • et al.
        Prediction of kidney drug clearance: a comparison of tubular secretory clearance and glomerular filtration rate.
        J Am Soc Nephrol. 2021; 32: 459-468
        • Stene G.B.
        • Helbostad J.L.
        • Amundsen T.
        • et al.
        Changes in skeletal muscle mass during palliative chemotherapy in patients with advanced lung cancer.
        Acta Oncol. 2015; 54: 340-348
        • Myers G.L.
        • Miller W.G.
        • Coresh J.
        • et al.
        Recommendations for improving serum creatinine measurement: a report from the laboratory working Group of the national kidney disease Education Program.
        Clin Chem. 2006; 52: 5-18
        • Stevens L.A.
        • Levey A.S.
        Use of the MDRD study equation to estimate kidney function for drug dosing.
        Clin Pharmacol Ther. 2009; 86: 465-467
        • Cockcroft D.W.
        • Gault M.H.
        Prediction of creatinine clearance from serum creatinine.
        Nephron. 1976; 16: 31-41
        • Michels W.M.
        • Grootendorst D.C.
        • Verduijn M.
        • et al.
        Performance of the Cockcroft-Gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size.
        Clin J Am Soc Nephrol. 2010; 5: 1003-1009
        • Levey A.S.
        • Coresh J.
        • Greene T.
        • et al.
        Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate.
        Ann Intern Med. 2006; 145: 247-254
        • Rhee J.
        • Kwon J.M.
        • Han S.H.
        • et al.
        Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration equations for estimating glomerular filtration rates in cancer patients receiving cisplatin-based chemotherapy.
        Kidney Res Clin Pract. 2017; 36: 342-348
        • Seronie-Vivien S.
        • Toullec S.
        • Malard L.
        • et al.
        Contribution of the MDRD equation and of cystatin C for renal function estimates in cancer patients.
        Med Oncol. 2006; 23: 63-73
        • Levey A.S.
        • Stevens L.A.
        • Schmid C.H.
        • et al.
        A new equation to estimate glomerular filtration rate.
        Ann Intern Med. 2009; 150: 604-612
        • Levey A.S.
        • de Jong P.E.
        • Coresh J.
        • et al.
        The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report.
        Kidney Int. 2011; 80: 17-28
        • Kilbride H.S.
        • Stevens P.E.
        • Eaglestone G.
        • et al.
        Accuracy of the MDRD (modification of diet in renal disease) study and CKD-EPI (CKD Epidemiology Collaboration) equations for estimation of GFR in the elderly.
        Am J Kidney Dis. 2013; 61: 57-66
        • Levey A.S.
        • Titan S.M.
        • Powe N.R.
        • et al.
        Kidney disease, race, and GFR estimation.
        Clin J Am Soc Nephrol. 2020; 15: 1203-1212
        • Levey A.S.
        • Tighiouart H.
        • Titan S.M.
        • et al.
        Estimation of glomerular filtration rate with vs without including patient race.
        JAMA Intern Med. 2020; 180: 793-795
        • Powe N.R.
        Black kidney function Matters: use or Misuse of race?.
        JAMA. 2020; 324: 737-738
        • Launay-Vacher V.
        • Chatelut E.
        • Lichtman S.M.
        • et al.
        Renal insufficiency in elderly cancer patients: international Society of Geriatric Oncology clinical practice recommendations.
        Ann Oncol. 2007; 18: 1314-1321
        • Matzke G.R.
        • Aronoff G.R.
        • Atkinson Jr., A.J.
        • et al.
        Drug dosing consideration in patients with acute and chronic kidney disease-a clinical update from Kidney Disease: improving Global Outcomes (KDIGO).
        Kidney Int. 2011; 80: 1122-1137
        • Stabuc B.
        • Vrhovec L.
        • Stabuc-Silih M.
        • et al.
        Improved prediction of decreased creatinine clearance by serum cystatin C: use in cancer patients before and during chemotherapy.
        Clin Chem. 2000; 46: 193-197
        • Hingorani S.
        • Pao E.
        • Schoch G.
        • et al.
        Estimating GFR in adult patients with hematopoietic cell transplant: comparison of estimating equations with an iohexol reference standard.
        Clin J Am Soc Nephrol. 2015; 10: 601-610
        • Bodnar L.
        • Wcislo G.B.
        • Smoter M.
        • et al.
        Cystatin C as a parameter of glomerular filtration rate in patients with ovarian cancer.
        Kidney Blood Press Res. 2010; 33: 360-367
        • Kos J.
        • Werle B.
        • Lah T.
        • et al.
        Cysteine proteinases and their inhibitors in extracellular fluids: markers for diagnosis and prognosis in cancer.
        Int J Biol Markers. 2000; 15: 84-89
        • Kimmel M.
        • Braun N.
        • Alscher M.D.
        Influence of thyroid function on different kidney function tests.
        Kidney Blood Press Res. 2012; 35: 9-17
        • Knight E.L.
        • Verhave J.C.
        • Spiegelman D.
        • et al.
        Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement.
        Kidney Int. 2004; 65: 1416-1421
        • Stevens L.A.
        • Schmid C.H.
        • Greene T.
        • et al.
        Factors other than glomerular filtration rate affect serum cystatin C levels.
        Kidney Int. 2009; 75: 652-660
        • Hudson J.Q.
        • Nolin T.D.
        Pragmatic Use of kidney function estimates for drug dosing: the Tide is Turning.
        Adv Chronic Kidney Dis. 2018; 25: 14-20
        • Janus N.
        • Launay-Vacher V.
        • Byloos E.
        • et al.
        Cancer and renal insufficiency results of the BIRMA study.
        Br J Cancer. 2010; 103: 1815-1821
        • Wright J.G.
        • Boddy A.V.
        • Highley M.
        • et al.
        Estimation of glomerular filtration rate in cancer patients.
        Br J Cancer. 2001; 84: 452-459
        • Holweger K.
        • Bokemeyer C.
        • Lipp H.P.
        Accurate measurement of individual glomerular filtration rate in cancer patients: an ongoing challenge.
        J Cancer Res Clin Oncol. 2005; 131: 559-567
        • Janowitz T.
        • Williams E.H.
        • Marshall A.
        • et al.
        New Model for estimating glomerular filtration rate in patients with cancer.
        J Clin Oncol. 2017; 35: 2798-2805
        • Chancharoenthana W.
        • Wattanatorn S.
        • Vadcharavivad S.
        • et al.
        Agreement and precision Analyses of various estimated glomerular filtration rate formulae in cancer patients.
        Sci Rep. 2019; 9: 19356
        • Garner A.E.
        • Barnfield M.C.
        • Waller M.L.
        • et al.
        Comparing glomerular filtration rate equations and the impact of different creatinine assays on the assessment of renal function in cancer patients.
        Ann Clin Biochem. 2019; 56: 266-274
        • Villasenor A.
        • Ballard-Barbash R.
        • Baumgartner K.
        • et al.
        Prevalence and prognostic effect of sarcopenia in breast cancer survivors: the HEAL Study.
        J Cancer Surviv. 2012; 6: 398-406
        • Latcha S.
        Pharmacokinetics of chemotherapeutic agents in kidney disease. In: Onco-Nephrology Curriculum, Washington, DC.
        • Frances B.
        • Gout R.
        • Monsarrat B.
        • et al.
        Further evidence that morphine-6 beta-glucuronide is a more potent opioid agonist than morphine.
        J Pharmacol Exp Ther. 1992; 262: 25-31
        • Nolin T.D.
        • Frye R.F.
        • Le P.
        • et al.
        ESRD impairs nonrenal clearance of fexofenadine but not midazolam.
        J Am Soc Nephrol. 2009; 20: 2269-2276
        • Marbury T.C.
        • Ruckle J.L.
        • Hatorp V.
        • et al.
        Pharmacokinetics of repaglinide in subjects with renal impairment.
        Clin Pharmacol Ther. 2000; 67: 7-15
        • Barnes J.N.
        • Williams A.J.
        • Tomson M.J.
        • et al.
        Dihydrocodeine in renal failure: further evidence for an important role of the kidney in the handling of opioid drugs.
        Br Med J (Clin Res Ed. 1985; 290: 740-742
        • Hori R.
        • Okumura K.
        • Kamiya A.
        • et al.
        Ampicillin and cephalexin in renal insufficiency.
        Clin Pharmacol Ther. 1983; 34: 792-798
        • De Martin S.
        • Orlando R.
        • Bertoli M.
        • et al.
        Differential effect of chronic renal failure on the pharmacokinetics of lidocaine in patients receiving and not receiving hemodialysis.
        Clin Pharmacol Ther. 2006; 80: 597-606
        • Paton T.W.
        • Cornish W.R.
        • Manuel M.A.
        • et al.
        Drug therapy in patients undergoing peritoneal dialysis. Clinical pharmacokinetic considerations.
        Clin Pharmacokinet. 1985; 10: 404-425
        • Faruqi A.
        • Tadi P.
        Cytarabine. StatPearl.
        • De Jonge M.E.
        • Huitema A.D.
        • Rodenhuis S.
        • et al.
        Clinical pharmacokinetics of cyclophosphamide.
        Clin Pharmacokinet. 2005; 44: 1135-1164
        • Firkin F.
        • Roncolato F.
        • Ho W.K.
        Dose-adjusted arsenic trioxide for acute promyelocytic leukaemia in chronic renal failure.
        Eur J Haematol. 2015; 95: 331-335
        • Baxter
        Bleomycin (bleomycin for injection).
        Package Insert, Deerfield (IL)2017
        • Watanabe R.
        • Takiguchi Y.
        • Moriya T.
        • et al.
        Feasibility of combination chemotherapy with cisplatin and etoposide for haemodialysis patients with lung cancer.
        Br J Cancer. 2003; 88: 25-30
        • Janus N.
        • Thariat J.
        • Boulanger H.
        • et al.
        Proposal for dosage adjustment and timing of chemotherapy in hemodialyzed patients.
        Ann Oncol. 2010; 21: 1395-1403
        • van Warmerdam L.J.
        • Rodenhuis S.
        • ten Bokkel Huinink W.W.
        • et al.
        The use of the Calvert formula to determine the optimal carboplatin dosage.
        J Cancer Res Clin Oncol. 1995; 121: 478-486
        • Shepherd S.T.
        • Gillen G.
        • Morrison P.
        • et al.
        Performance of formulae based estimates of glomerular filtration rate for carboplatin dosing in stage 1 seminoma.
        Eur J Cancer. 2014; 50: 944-952
        • Chatelut E.
        • Rostaing L.
        • Gualano V.
        • et al.
        Pharmacokinetics of carboplatin in a patient suffering from advanced ovarian carcinoma with hemodialysis-dependent renal insufficiency.
        Nephron. 1994; 66: 157-161
        • English M.W.
        • Lowis S.P.
        • Peng B.
        • et al.
        Pharmacokinetically guided dosing of carboplatin and etoposide during peritoneal dialysis and haemodialysis.
        Br J Cancer. 1996; 73: 776-780
        • Motzer R.J.
        • Niedzwiecki D.
        • Isaacs M.
        • et al.
        Carboplatin-based chemotherapy with pharmacokinetic analysis for patients with hemodialysis-dependent renal insufficiency.
        Cancer Chemother Pharmacol. 1990; 27: 234-238
        • Yanagawa H.
        • Takishita Y.
        • Bando H.
        • et al.
        Carboplatin-based chemotherapy in patients undergoing hemodialysis.
        Anticancer Res. 1996; 16: 533-535
        • Inoue A.
        • Saijo Y.
        • Kikuchi T.
        • et al.
        Pharmacokinetic analysis of combination chemotherapy with carboplatin and etoposide in small-cell lung cancer patients undergoing hemodialysis.
        Ann Oncol. 2004; 15: 51-54
        • Veal G.J.
        • English M.W.
        • Grundy R.G.
        • et al.
        Pharmacokinetically guided dosing of carboplatin in paediatric cancer patients with bilateral nephrectomy.
        Cancer Chemother Pharmacol. 2004; 54: 295-300
        • Guddati A.K.
        • Joy P.S.
        • Marak C.P.
        Dose adjustment of carboplatin in patients on hemodialysis.
        Med Oncol. 2014; 31: 946
        • Perry J.J.
        • Fleming R.A.
        • Rocco M.V.
        • et al.
        Administration and pharmacokinetics of high-dose cyclophosphamide with hemodialysis support for allogeneic bone marrow transplantation in acute leukemia and end-stage renal disease.
        Bone Marrow Transpl. 1999; 23: 839-842
        • Smith G.A.
        • Damon L.E.
        • Rugo H.S.
        • et al.
        High-dose cytarabine dose modification reduces the incidence of neurotoxicity in patients with renal insufficiency.
        J Clin Oncol. 1997; 15: 833-839
        • Hospira
        Etopophos (etoposide for injection).
        Package Insert, Lake Forest (IL)2021
        • Kaijser G.P.
        • Beijnen J.H.
        • Bult A.
        • et al.
        Ifosfamide metabolism and pharmacokinetics (review).
        Anticancer Res. 1994; 14: 517-531
        • Latcha S.
        • Maki R.G.
        • Schwartz G.K.
        • et al.
        Ifosfamide may be safely used in patients with end stage renal disease on hemodialysis.
        Sarcoma. 2009; 2009: 575629
        • Eli Lily and company
        ALIMTA (pemetrexed for injections).
        Package Insert, Indianapolis, IN2019
        • Lam M.S.H.
        • Ignoffo R.J.
        A guide to clinically relevant drug interactions in oncology.
        J Oncol Pharm Pract. 2003; 9: 45-85
        • Jhaveri K.D.
        • Flombaum C.
        • Shah M.
        • et al.
        A retrospective observational study on the use of capecitabine in patients with severe renal impairment (GFR <30 mL/min) and end stage renal disease on hemodialysis.
        J Oncol Pharm Pract. 2012; 18: 140-147
        • Mikhael J.
        • Manola J.
        • Dueck A.C.
        • et al.
        Lenalidomide and dexamethasone in patients with relapsed multiple myeloma and impaired renal function: PrE1003, a PrECOG study.
        Blood Cancer J. 2018; 8: 86
        • Genentech
        AVASTIN (bevacizumab for injection).
        Package Insert, San Francisco, CA2020
        • Garnier-Viougeat N.
        • Rixe O.
        • Paintaud G.
        • et al.
        Pharmacokinetics of bevacizumab in haemodialysis.
        Nephrol Dial Transpl. 2007; 22: 975
        • Thariat J.
        • Azzopardi N.
        • Peyrade F.
        • et al.
        Cetuximab pharmacokinetics in end-stage kidney disease under hemodialysis.
        J Clin Oncol. 2008; 26: 4223-4225
        • Krens L.L.
        • Baas J.M.
        • Guchelaar H.J.
        • et al.
        Pharmacokinetics and safety of panitumumab in a patient with chronic kidney disease.
        Cancer Chemother Pharmacol. 2018; 81: 179-182
        • Jhaveri K.D.
        • Wanchoo R.
        • Sakhiya V.
        • et al.
        Adverse renal effects of novel molecular oncologic targeted therapies: a narrative review.
        Kidney Int Rep. 2016; 2: 108-123
        • Kitchlu A.
        • Jhaveri K.D.
        • Sprangers B.
        • et al.
        Immune checkpoint inhibitor use in patients with end-stage kidney disease: an analysis of reported cases and literature review.
        Clin Kidney J. 2021; 14: 2012-2022
        • Hirsch J.S.
        • Wanchoo R.
        • Ng J.H.
        • et al.
        Use of immune checkpoint inhibitors in end stage kidney disease patients: single center experience and review of the literature.
        Kidney360. 2020; 1: 399-402
        • Murakami N.
        • Mulvaney P.
        • Danesh M.
        • et al.
        A multi-center study on safety and efficacy of immune checkpoint inhibitors in cancer patients with kidney transplant.
        Kidney Int. 2020; 100: 196-205
        • Guddati A.K.
        • Joy P.S.
        • Marak C.P.
        Dose adjustment of carboplatin in patients on hemodialysis.
        Med Oncol. 2014; 31: 848
        • Kumar N.
        • Shirali A.C.
        What is the best therapy for toxicity in the setting of methotrexate-associated acute kidney injury: high-flux hemodialysis or carboxypeptidase G2?.
        Semin Dial. 2014; 27: 226-228
        • Truong H.
        • Leung N.
        Fixed-dose glucarpidase for toxic methotrexate levels and acute kidney injury in adult lymphoma patients: case series.
        Clin Lymphoma Myeloma Leuk. 2021; 21: e497-e502
        • Zhu X.
        • Wu S.
        • Dahut W.L.
        • et al.
        Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis.
        Am J Kidney Dis. 2007; 49: 186-193
        • Eremina V.
        • Jefferson J.A.
        • Kowalewska J.
        • et al.
        VEGF inhibition and renal thrombotic microangiopathy.
        N Engl J Med. 2008; 358: 1129-1136
        • Kazazi-Hyseni F.
        • Beijnen J.H.
        • Schellens J.H.
        Oncologist. 2010; 15: 819-825
        • Jhaveri K.D.
        • Sakhiya V.
        • Wanchoo R.
        • et al.
        Renal effects of novel anticancer targeted therapies: a review of the Food and drug administration adverse event reporting System.
        Kidney Int. 2016; 90: 706-707
        • Perazella M.A.
        • Shirali A.C.
        Immune checkpoint inhibitor nephrotoxicity: what do we know and what should we do?.
        Kidney Int. 2020; 97: 62-74
        • Perazella M.A.
        • Sprangers B.
        AKI in patients receiving immune checkpoint inhibitors.
        Clin J Am Soc Nephrol. 2019; 14: 1077-1079
        • McMahon B.A.
        • Rosner M.H.
        GFR measurement and chemotherapy dosing in patients with kidney disease and cancer.
        Kidney360. 2020; 1: 141-150