ABSTRACT
Pralatrexate (PDX) is a folate antagonist structurally similar to methotrexate (MTX). Unlike MTX, it is currently not known whether PDX exhibits delayed clearance and heightened toxicity in the setting of fluid overload. A specific serum assay for PDX is not commercially available. To our knowledge, we report the first case using an MTX serum assay as a surrogate for PDX concentrations to avoid a potential drug-drug interaction with pralatrexate. We describe a 76-year-old man with refractory cutaneous T-cell lymphoma who began therapy with weekly PDX 15 mg/m(2) intravenous infusions on days 1, 8, and 15 of a 28-day cycle. He subsequently developed mucositis, a moderate right-sided pleural effusion, and peripheral edema over the next 5 weeks. Aggressive diuresis with furosemide was initiated, which was then withheld the day before his next PDX dose to avoid a potential drug-drug interaction between PDX and furosemide. His baseline MTX/PDX concentration (measured prior to administration of the cycle 2, week 2 PDX dose) was less than 0.20 µmol/L (i.e., undetectable). After PDX administration, his 1-hour peak MTX/PDX concentration increased to 0.58 µmol/L. Aggressive diuresis was withheld until his MTX/PDX concentration was undetectable, 43.5 hours later. PDX is more potent than MTX and displays similar pharmacokinetic properties. PDX concentrations using the serum MTX assay reflect lower values than those reported from PDX-specific assays in clinical studies. Because PDX is approved by the U.S. Food and Drug Administration for the treatment of uncommon malignancies, it is unlikely that a specific assay will be commercially developed. We propose that the MTX serum assay has merit for use in determining when to reinstate possible interacting drug therapies such as loop diuretics.
Subject(s)
Aminopterin/analogs & derivatives , Folic Acid Antagonists/blood , Lymphoma, T-Cell, Cutaneous/blood , Skin Neoplasms/blood , Aged , Aminopterin/administration & dosage , Aminopterin/blood , Aminopterin/pharmacokinetics , Aminopterin/therapeutic use , Drug Interactions , Drug Monitoring , Folic Acid Antagonists/administration & dosage , Folic Acid Antagonists/pharmacokinetics , Folic Acid Antagonists/therapeutic use , Furosemide/administration & dosage , Furosemide/adverse effects , Furosemide/therapeutic use , Humans , Infusions, Intravenous , Lymphoma, T-Cell, Cutaneous/drug therapy , Lymphoma, T-Cell, Cutaneous/physiopathology , Male , Methotrexate/analysis , Methotrexate/chemistry , Pleural Effusion/drug therapy , Pleural Effusion/etiology , Reagent Kits, Diagnostic , Skin Neoplasms/complications , Skin Neoplasms/drug therapy , Skin Neoplasms/physiopathology , Sodium Potassium Chloride Symporter Inhibitors/administration & dosage , Sodium Potassium Chloride Symporter Inhibitors/adverse effects , Sodium Potassium Chloride Symporter Inhibitors/therapeutic use , Treatment OutcomeABSTRACT
PURPOSE: Antral follicle count (AFC) is used as a marker of ovarian response. We assessed its value in predicting pregnancy outcomes in ovum donation cycles by retrospective review. METHODS: Oocyte donors (n = 94) underwent ovarian hyperstimulation using rFSH and GnRH-antagonists. Recipients were synchronized using GnRH-agonist down-regulation followed by fixed dose of estrogen and progesterone following hCG. Outcomes measured included correlation of AFC to pregnancy outcomes and cycle characteristics in those with and without clinical and ongoing-delivered cycles. RESULTS: AFC significantly correlated with clinical [Exp beta 1.12; 95% CI: 1.02-1.23, p < 0.05] and ongoing-delivered pregnancy [Exp beta 1.10; 95% CI: 1.01-1.20, p < 0.05]. Significantly greater AFC, total and M-2 oocytes, and cycles resulting in cryopreserved embryos were seen in clinical and ongoing-delivered cycles. CONCLUSIONS: AFC predicts cycle stimulation responses and clinical outcomes and may serve as a guide for dosing protocols and in choosing to proceed with the most optimal cycle.
