levoleucovorin and Renal-Insufficiency--Chronic

Methotrexate-induced epidermal necrosis (MEN) is a rare but life-threatening cutaneous reaction that mimics Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).. To investigate the clinicopathology, risk factors, and prognostic factors of MEN.. We enrolled 24 patients with MEN and 150 controls and analyzed the demographics, pathology, and plasma concentrations of methotrexate (MTX).. Patients with MEN showed extensive skin necrosis (mean, 33.2% total body surface area) but no target lesions. The histopathology displayed keratinocyte dystrophy. Early signs of MEN included painful skin erosions, oral ulcers, and leukopenia/thrombocytopenia. Although 79.2% patients received leucovorin treatment, there was 16.7% mortality. Risk factors for MEN included older age (>60 years), chronic kidney disease, and high initial dosage of MTX without folic acid supplementation. Renal insufficiency delayed MTX clearance. Severe renal disease and leukopenia predicted poor prognosis in MEN, but none of the SCORe of Toxic Epidermal Necrosis criteria were associated with mortality of MEN.. The study was limited by the small sample size.. MEN exhibited distinct clinicopathologic features from SJS/TEN. Recognition of the early signs and prognostic factors is important, because the rapid institution of leucovorin may be helpful. To reduce the risk of MEN, physicians should avoid prescribing MTX to high-risk patients and titrate the dosage slowly upward with folic acid supplementation.

Topics: Adult; Age Factors; Aged; Body Surface Area; Case-Control Studies; Drug Eruptions; Epidermis; Female; Folic Acid Antagonists; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Necrosis; Prognosis; Renal Insufficiency, Chronic; Survival Rate; Vitamin B Complex

A 71-year-old man with predialysis terminal renal insufficiency experienced peritoneal dissemination 1.5 years after low anterior resection for advanced rectal cancer. He received FOLFIRI therapy (70% dose); he achieved partial response (PR) under computed tomography and stable disease (SD) was maintained over a long term. Although Grade 3 myelosuppression was occasionally noted, he was treated with FOLFIRI for 2 years without other severe complications and without requiring the initiation of hemodialysis. After the initiation of hemodialysis, FOLFIRI treatment was continued for 1 year until progressive disease (PD). He received mFOLFOX6 as second-line therapy for 6 months, followed by LV-5-FU and a molecular targeting agent. These treatments prolonged his survival for 1 year and 8 months. FOLFIRI can be administered as an effective first-line therapy even for patients with predialysis terminal renal impairment without major renal damage. FOLFOX and molecular targeting agents should be made available and prolonged survival can be expected for advanced colorectal cancer patients with terminal renal disease after the initiation of hemodialysis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Dialysis; Fatal Outcome; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Rectal Neoplasms; Recurrence; Renal Insufficiency, Chronic; Time Factors