MON-253 PEMETREXED INDUCED INTERSTITIAL NEPHRITIS AMONG PATIENTS WITH METASTATIC NON-SMALL CELL ADENOCARCINOMA OF THE LUNGS (NSCLC)

Abstract

Pemetrexed, a folate antagonistic chemotherapy, was approved for metastatic NSCLC since 2008. We documented 3 cases of biopsy-proven interstitial nephritis treated with pemetrexed. Interstitial nephritis had been described but incidence is unknown. Case 1: A 48-year-old African man with obesity and glucose intolerance presented with protracted cough. Investigation showed locally advanced NSCLC (EGFR +ve). Treatment with gefitinib failed showing progression. He developed right malignant pleural effusion and bilateral lung nodules. Baseline serum creatinine was 120 µmol/L. Pemetrexed was started 14 months after diagnosis. He received dexamethasone initially. Disease progression was halted after 4 cycles. Serum creatinine rose to 188 µmol/L after treatment for 20 months with interruptions. Renal biopsy showing chronic tubulointerstitial nephritis. Pemetrexed was stopped and azathioprine was given for several weeks. Renal function stabilized. Chemotherapy was changed to erlotinib, but he died 6 months later. Case 2: A 63-year-old Caucasian lady with chronic smoking and type I diabetes mellitus was diagnosed with metastatic NSCLC with left lung masses, EGFR/ALK negative. She was started on cis-platinum/pemetrexed. The baseline serum creatinine was 70 µmol/L. She received 4 doses of cisplatin/pemetrexed with good response. Then she was maintained on pemetrexed and received 4 more cycles. her serum creatinine increased to 296 µmol/L. She had a percutaneous renal biopsy showing acute interstitial nephritis most likely from pemetrexed. Confounding drugs include esomeprazole and venlafaxine. She received 4 months of tapering prednisone with cessation of Pemetrexed. The serum creatinine stabilized between 210-230 µmol/L. Follow-up staging showed little progression of her pulmonary locally advanced metastasis. Case 3: A 65-year-old female chronic smoker was diagnosed to have metastatic NSCLC (EGFR/ALK negative) with large lung masses, supraclavicular lymph nodes, occipital lytic lesion and 20 kg weight loss. Baseline serum creatinine was 49 µmol/L. She was started on carboplatin/pemetrexed. She had 4 courses in 3 months and tolerated treatment very well. She gained weight with good appetite and energy. She was started on maintenance pemetrexed. 4 months after starting chemotherapy, serum creatinine rose to 149 µmol/L. Pemetrexed was halted and renal biopsy showed mild active tubulointerstitial nephritis. Serum creatinine stabilized at 100 µmol/L. We proposed to restart pemetrexed with covering prednisone. Unfortunately, the metastatic lesions led to her demise quickly. Our 3 cases indicated beneficial effect of pemetrexed for metastatic NSCLC. However, it can lead to tubulointerstitial nephritis and loss of renal function. Cessation of pemetrexed terminated the beneficial effects and led to metastatic progression. Prednisone or azathioprine can be considered for immunosuppression while patients continued pemetrexed, deriving beneficial therapeutic effect. A pemetrexed registry could be helpful to document incidence, clinical course and treatment possibilities of tubulointerstitial nephritis.