Pemetrexed induced acute kidney injury in patients with non-small cell lung cancer: reversible and chronic renal damage
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.
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.
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).
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.
KeywordsAcute kidney injury Bone marrow toxicity Not small cell lung cancer Pemetrexed
- 1.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):2636–2644CrossRefPubMedGoogle Scholar
- 2.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):756–763CrossRefPubMedGoogle Scholar
- 3.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):215–223CrossRefPubMedGoogle Scholar
- 6.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):3217–3224CrossRefPubMedGoogle Scholar
- 8.http://www.drugs.com/pro/alimta.html. Accessed 26 Dec 2012
- 9.http://www.uptodate.com. Accessed 27 Feb 2014
- 12.http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Accessed 27 Feb 2014
- 13.http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/021462lbl.pdf. Accessed 27 Feb 2014
- 14.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 31:2895–2902CrossRefPubMedGoogle Scholar
- 20.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)Google Scholar