Secondary Capillary Leak Syndrome Related to Pemetrexed Exposure

Abstract

We read the article by Glezerman et al1Glezerman I.G. Pietanza M.C. Miller V. et al.Kidney tubular toxicity of maintenance pemetrexed therapy.Am J Kidney Dis. 2011; 58: 817-820Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar with great interest. We would like to report a patient who developed systemic capillary leak syndrome due to pemetrexed. A 74-year-old white man with non–small cell lung cancer had poor response to a carboplatin-paclitaxel chemotherapy regimen, so it was changed to pemetrexed, 500 mg/m2. Within several days he developed moderate-size pericardial and pleural effusion, as well as severe edema of the face, abdominal wall, and lower and upper extremities; he also acutely gained 36 pounds of weight. Hypotension necessitated discontinuation of antihypertensive medications and administration of intravenous fluids. Noninvasive evaluation showed no evidence of infection and normal cardiac, hepatic, adrenal, and thyroid function. There was no hematuria or proteinuria on urinalysis. His serum albumin level decreased from 4.0 to 2.0 g/dL (40 to 20 g/L) and his serum creatinine concentration increased from within the reference range to 1.9 mg/dL (corresponding to an estimated glomerular filtration rate of 34 mL/min/1.73 m2 [0.57 mL/s/1.73 m2] by the MDRD equation); FENa was less than 1.0%. With avoidance of further pemetrexed therapy, he had complete resolution of his systemic capillary leak syndrome over a 1-month period. Systemic capillary leak syndrome is characterized by episodic attacks of systemic capillary permeability, resulting in fluid and protein leakage from the intravascular space to the interstitium and pericardial, pleural, and peritoneal spaces; hypotension; and hemoconcetration.2Clarkson B. Thompson D. Horwith M. et al.Cyclical edema and shock due to increased capillary permeability.Am J Med. 1960; 29: 193-216Abstract Full Text PDF PubMed Scopus (279) Google Scholar Secondary capillary leak syndrome, as occurred in this patient, can result from medications and toxins, and can have any of the features of systemic capillary leak syndrome.3Gousseff M. Arnaud L. Lambert M. et al.The systemic capillary leak syndrome: a case series of 28 patients from a European registry.Ann Intern Med. 2011; 154: 464-471Crossref PubMed Scopus (105) Google Scholar Although pemetrexed-induced fluid retention and eyelid edema have been reported,4Kurata T. Tamura K. Okamoto I. et al.Pemetrexed-induced edema of the eyelid.Lung Cancer. 2006; 54: 241-242Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar, 5Schallier D. Decoster L. Fontaine C. et al.Pemetrexed-induced eyelid edema: incidence and clinical manifestations.Anticancer Res. 2010; 30: 5185-5188PubMed Google Scholar, 6Bastos D.A. Calabrich A. Katz A. Pemetrexed-induced fluid retention.J Thorac Oncol. 2010; 5: 752Crossref PubMed Scopus (11) Google Scholar, 7D'Angelo S.P. Kris M.G. Pietanza M.C. et al.A case series of dose-limiting peripheral edema observed in patients treated with pemetrexed.J Thorac Oncol. 2011; 6: 624-626Crossref PubMed Scopus (14) Google Scholar this is the first report of pemetrexed-induced systemic capillary leak syndrome to our knowledge. Awareness within the medical community of this side effect is important. Financial Disclosure: The authors declare that they have no relevant financial interests. Kidney Tubular Toxicity of Maintenance Pemetrexed TherapyAmerican Journal of Kidney DiseasesVol. 58Issue 5PreviewPemetrexed is an antifolate agent approved for the treatment of advanced lung cancer. Major side effects include myelosuppression and neutropenia. Three patients developed kidney disease while being treated with maintenance pemetrexed. Kidney biopsy specimens showed tubulointerstitial injury with tubular simplification, shrinkage, loss of brush border, and tubular atrophy in a more advanced case. Kidney function remained impaired, but stable, after discontinuation of pemetrexed therapy in all cases. Full-Text PDF In Reply to ‘Secondary Capillary Leak Syndrome Related to Pemetrexed Exposure’American Journal of Kidney DiseasesVol. 59Issue 4PreviewMaroz and Weiner report a case of systemic capillary leak syndrome associated with administration of pemetrexed and characterized by peripheral and visceral edema, hypotension, hypoalbuminemia, and acute kidney injury.1 This syndrome is a relatively rare condition with 126 cases reported in the literature between 1960 and 2010. It is characterized by unexplained episodes of capillary hyperpermeability manifesting as edema, hypoalbuminemia, and shock.2 Although the authors purport that this is the first report of pemetrexed-related systemic capillary leak syndrome, a number of cases of fluid retention during therapy with pemetrexed have been reported in the literature. Full-Text PDF