Abstract
Background
Pemetrexed (Alimta®) (PEM) is an antifolate antineoplastic agent effective in several tumor types, such as non-small-cell lung cancer (NSCLC) and mesothelioma, among others. It is almost exclusively excreted by the kidney and an eGFR lower 45 mL/min is a contraindication for its use: above this level PEM administration is considered safe and dose adjustment is not required. Although there are some reported cases of PEM-induced renal injury, its incidence and the negative effects on patients’ outcome has not been systematically evaluated.
Methods
We report a retrospective evaluation on the incidence of PEM-induced renal injury in patients affected by NSCLC. Between June 2010 and March 2012 a total of 38 NSCLC patients were treated at our hospital. In 29 of them other possible cause of renal injury were excluded and thus they were eligible to be analysed.
Results
Although by protocol all of them had eGFR >45 mL/min at baseline, six patients (average eGFR 56.2 ± 11.5 mL/min/1.73 m2) developed AKI (21 %). In these six patients PEM-induced myelosuppression was more severe and hospitalization was longer. Kidney function completely recovered in four patients whereas in the other two deterioration of renal function was irreversible. The number of patients with baseline eGFR <60 mL/min/1.73 m2 was higher (4/6) in the group that developed AKI as compared to those who did not (6/23) (p < 0.05).
Conclusions
There is no clear cut eGFR above which PEM may be used without potential risks of renal toxicity. If PEM has to be used, all the coexisting risk factors for AKI should be possibly corrected.
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References
Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P (2003) Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 21(14):2636–2644
Santoro A, O’Brien ME, Stahe RA, Nackaerts K, Baas P, Karthaus M, Eberhardt W, Paz-Ares L, Sundstrom L, Liu Y, Ripoche V, Blatter J, Visseren-Gru CM, Manegold C (2008) Pemetrexed plus cisplatin or pemetrexed plus carboplatin for chemonaıve patients with malignant pleural mesothelioma: results of the international expanded access program. J Thorac Oncol 3(7):756–763
Schuette WH, Gröschel A, Sebastian M, Andreas S, Müller T, Schneller T, Guetz S, Eschbach C, Bohnet S, Leschinger MI, Reck M (2013) A randomized phase II study of pemetrexed in combination with cisplatin or carboplatin as first-line therapy for patients with locally advanced or metastatic non-small-cell lung cancer. Clin Lung Cancer 14(3):215–223
Socinski MA, Stinchcombe TE, Hayes DN (2005) The evolving role of pemetrexed (Alimta) in lung cancer. Semin Oncol 32(2 Suppl 2):16–22 (Review)
Ciuleanu T, Brodowicz T, Zielinski C et al (2009) Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet 374(9699):1432–1440
Grønberg BH, Bremnes RM, Fløtten O et al (2009) Phase III study by the Norwegian Lung Cancer Study Group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 27(19):3217–3224
Hanna N, Shepherd FA, Fossella FV et al (2004) Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol 22(9):1589–1597
http://www.drugs.com/pro/alimta.html. Accessed 26 Dec 2012
http://www.uptodate.com. Accessed 27 Feb 2014
Levin A, Warnock DG, Mehta RL et al (2007) Improving outcomes from acute kidney injury: report of an initiative. Am J Kidney Dis 50:1–4
Jassem J, Ramlau R, Santoro A et al (2008) Phase III trial of pemetrexed plus best supportive care compared with best supportive care in previously treated patients with advanced malignant pleural mesothelioma. J Clin Oncol 26(10):1698–1704
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Accessed 27 Feb 2014
http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/021462lbl.pdf. Accessed 27 Feb 2014
Paz-Ares LG, De Marinis F, Dediu M et al (2013) PARAMOUNT: final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol 31:2895–2902
Glezerman IG, Pietanza MC, Miller V, Seshan SV (2011) Kidney tubular toxicity of maintenance pemetrexed therapy. Am J Kidney Dis 58(5):817–820
Vootukuru V, Liew YP, Nally JV Jr (2006) Pemetrexed-induced acute renal failure, nephrogenic diabetes insipidus, and renal tubular acidosis in a patient with non-small cell lung cancer. Med Oncol 23:419–422
Michels J, Spano JP, Brocheriou I, Deray G, Khayat D, Izzedine H (2009) Acute tubular necrosis and interstitial nephritis during pemetrexed therapy. Case Rep Oncol 2:53–56
Stavroulopoulos A, Nakopoulou L, Xydakis AM, Aresti V, Nikolakopoulou A, Klouvas G (2010) Interstitial nephritis and nephrogenic diabetes insipidus in a patient treated with pemetrexed. Ren Fail 32:1000–1004
Porta JM, Vicente de Vera Floristán C, Inglán PB, Jericó JF (2009) Acute renal failure associated with Pemetrexed (Alimta®). Nefrologia 29:610–611
Chauvet S, Courbebaisse M, Ronco P, Plaisier E. Pemetrexed-induced acute kidney injury leadind to chronic kidney disease. Clin Nephrol. 2014 (Epub ahead of print)
Perazella MA, Markowitz GS (2008) Bisphosphonate nephrotoxicity. Kidney Int 74:1385–1393
Bodmer M, Amico P, Mihatsch MJ et al (2007) Focal segmental glomerulosclerosis associated with long-term treatment with zoledronate in a myeloma patient. Nephrol Dial Transplant 22:2366–2370
Barri YM, Munshi NC, Sukumalchantra S et al (2004) Podocyte injury associated glomerulopathies induced by pamidronate. Kidney Int 65:634–641
Markowitz GS, Appel GB, Fine PL et al (2001) Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. J Am Soc Nephrol 12:1164–1172
Desikan R, Veksler Y, Raza S et al (2002) Nephrotic proteinuria associated with high-dose pamidronate in multiple myeloma. Br J Haematol 119:496–499
McKeage MJ (1995) Comparative adverse effect profiles of platinum drugs. Drug Saf. 13:228–244
Hannemann J, Baumann K (1990) Nephrotoxicity of cisplatin, carboplatin and transplatin. Arch Toxicol 64:339–400
Acknowledgments
The authors express special thanks and gratitude to Elvira Castellini for her help and assistance.
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Rombolà, G., Vaira, F., Trezzi, M. et al. Pemetrexed induced acute kidney injury in patients with non-small cell lung cancer: reversible and chronic renal damage. J Nephrol 28, 187–191 (2015). https://doi.org/10.1007/s40620-014-0117-5
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DOI: https://doi.org/10.1007/s40620-014-0117-5