Abstract C228: Renal insufficiency secondary to Erlotinib: Is it real?
Authors: Nabi Sumbal , Adjei Alex A. , Prah Joseph , Ramnath Nithya , Schwartz James , Lennon Kevin , Grabek Michele Silsby , Dy Grace K. 
Published: June 2012

Abstract
Objective: We conducted a retrospective chart review to assess the extent of renal insufficiency noted in patients receiving Erlotinib for refractory/relapsed non small cell lung cancer at our Institute.
Methods: We reviewed the charts of 285 patients at Roswell Park Cancer Institute, who received Erlotinib for varying durations of time during 2004 and 2009. Baseline and post-erlotinib serum creatinine (SCr) and serum creatinine clearance (SCrCl) levels were noted. Cases with worsening of serum creatinine levels during treatment with erlotinib were isolated. Extent of worsening, associated co-morbidities and medications and other factors possibly contributing to renal dysfunction were noted along with improvement in renal status after discontinuation of erlotinib.
Results: Of the 175 patients with data available for evaluation, 21(12%) had worsening of their baseline SCr level while on erlotinib. 13(62%) of the patients with renal insufficiency had documented hypertension as co morbidity and were on anti-hypertensives including diuretics and ACE inhibitors. 8(38%) were diagnosed with diabetes mellitus and 6(28%) had coronary artery disease. 6(28%) patients had established chronic renal insufficiency (CRI) at baseline and had worsening after initiation of erlotinib. 1 patient had CRI secondary to prior history of renal cell cancer and was post nephrectomy. 1 patient had evidence of autoimmune disorder with Reynaud's phenomenon and polycystic kidneys. Another patient had history of lupus without evidence of CRI at baseline. 6(28%) concomitantly had diarrhea as a side-effect with erlotinib and in at least 3(14%) patients was the reason for discontinuation of further drug administration. In the remainder of the patients, the cause of discontinuation of erlotinib was progression in 13(52%), severe rash in 2(9%) and 3(14%) were still on the drug at the time of this analysis. Overall 5(21%) of patients with renal insufficiency after initiation of erlotinib did not have any other confounding factors identified. The onset of worsening renal status ranged from 14 days up to 333 days with a mean of 60 days. Baseline SCrCl of patients ranged from 26.2 to 100.5 ml/min with a mean of 49.8 and baseline SCr levels ranged from 0.9 to 2.4 mg/dl. Post therapy SCrCl in patients with worsening ranged from 18.5 to 59.8 with a mean of 35.9 and SCr levels from 1.3 to 3.4. Hence mean decline in SCrCl in these patients was by approximately 14 ml/min and serum creatinine of 0.5mg/dl. Of the 19 patients not currently on erlotinib any more, 12(63%) were noted to have improvement in SCrCl in mean of 33 days.
Conclusion: The incidence of isolated renal insufficiency due to erlotinib is rare but does exist. Most often it is confounded with preexisting hypertension and diabetes mellitus leading to baseline chronic renal dysfunction and multiple other medications or concomitant diarrhea as a side effect of erlotinib leading to pre-renal worsening of kidney function.
Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C228.