Risk factors of nephrotoxicity of maintenance pemetrexed in patients with metastatic non-squamous non-small cell carcinoma of lung

Background: Nephrotoxicity is one of the concerns of prolonged maintenance therapy with pemetrexed. No reversible risk factors for pemetrexed-induced nephrotoxicity have been identified in previous studies. Identification of such factors would be clinically meaningful to maximize the chemotherapeutic benefits by avoiding premature termination of maintenance therapy which might otherwise result from the development of renal impairment. Methods: This was a retrospective single-center cohort study conducted in Queen Mary Hospital in Hong Kong. The study included 134 patients with advanced stage non-squamous NSCLC that received first line pemetrexedplatinum doublets followed by maintenance pemetrexed. The primary endpoint was the occurrence of nephrotoxicity. The risk factors of nephrotoxicity were identified. Results: Presence of non-evacuated third-space fluid during treatment course (OR 4.185, 95% CI = 1.150-15.191, p-value 0.030), the use of cisplatin (instead of carboplatin) during the induction phase (OR 8.761, 95% CI = 1.684-45.577, p-value 0.010) and receiving more than 15 cycles of maintenance pemetrexed (OR 3.839, 95% CI = 1.022-14.413, p-value 0.046) were identified as independent risk factors to the development of nephrotoxicity associated with maintenance pemetrexed use. Conclusions: In order to reduce the risk of development of nephrotoxicity in NSCLC patient receiving first-line pemetrexed-platinum doublets, third-space fluid should be evacuated and carboplatin should be chosen over cisplatin whenever possible.

Automated summary

The independent risk factors for pemetrexed-induced nephrotoxicity in maintenance therapy were identified as non-evacuated third-space fluid, use of cisplatin during induction, and receiving more than 15 cycles of maintenance pemetrexed. To reduce the risk of nephrotoxicity, third-space fluid should be evacuated and carboplatin preferred over cisplatin whenever possible.