Retrospective evaluation of sodium acetate use for urine alkalinization in patients receiving high dose methotrexate.

PURPOSE: Methotrexate is an antifolate agent used in treatment of several malignancies. Many toxicities accompany methotrexate that are minimized with urine alkalinization. Parenteral sodium bicarbonate is the historical standard alkalinizing agent, but use has been limited by intermittent shortages. However, intravenous sodium acetate may be considered as a chemically equivalent alternative. The primary objective of this study is to determine the efficacy of sodium acetate versus sodium bicarbonate for urine alkalinization for high-dose methotrexate (HDMTX). METHODS: This is a retrospective cohort study including adults admitted to Barnes-Jewish Hospital to receive HDMTX for lymphoma, breast cancer with leptomeningial spread, or osteosarcoma. Patients must have received intravenous sodium acetate or sodium bicarbonate alkalinization. RESULTS: Of 192 HDMTX encounters, 154 (sodium bicarbonate, n = 86; sodium acetate, n = 68) were evaluated for efficacy and safety. Safety outcomes were not significantly different between groups except for higher peak methotrexate level in the bicarbonate group (2.9 mcmol/L vs. 1.7 mcmol/L, p = 0.023), and increased incidence of grade 3-4 ALT in the sodium bicarbonate group (23.5% vs. 9%, p = 0.02). Time from alkalinizer initiation to pH ≥7 was significantly shorter with sodium bicarbonate (4 vs. 5.15 h, p = 0.021). Nonetheless, outcomes such as length of stay (4.4 vs. 4 days respectively, p = 0.037) and time to methotrexate clearance (3.6 vs. 3.2 days respectively, p = 0.023) reveal that inpatient time was shorter with sodium acetate overall. CONCLUSION: This retrospective analysis suggests that sodium acetate has similar efficacy and safety to sodium bicarbonate for alkalinization and may be considered as an alternative in future shortage situations.

Evaluation of thiamine for the prevention of ifosfamide-induced encephalopathy.

STUDY OBJECTIVE: To determine whether thiamine prophylaxis decreases the incidence of ifosfamide-induced encephalopathy in patients receiving ifosfamide for the treatment of lymphoma. DESIGN: Retrospective, multi-center, cohort study. PATIENTS: A total of 73 patients who received 187 total cycles of ifosfamide, carboplatin, and etoposide chemotherapy for the treatment of lymphoma were included in this study. Forty-four of these patients (114 cycles) were included in the no-thiamine group and 29 (65 cycles) in the thiamine group. MEASUREMENTS AND MAIN RESULTS: The incidence of ifosfamide-induced encephalopathy was measured using the Common Terminology Criteria for Adverse Events and documentation in the patient chart. Regarding the primary endpoint of ifosfamide-induced encephalopathy, eight patients (18.2%) in the no-thiamine group and three patients (10.3%) in the thiamine group experienced an event (p = 0.5087). No patient experienced more than one neurotoxic event. CONCLUSION: There was no significant difference found in the incidence of ifosfamide-induced encephalopathy with the addition of thiamine prophylaxis in patients receiving ifosfamide, carboplatin, and etoposide-based chemotherapy regimens for lymphoma. Larger, prospective studies assessing the use of thiamine prophylaxis in this patient population are warranted to better assess its impact on the incidence of ifosfamide-induced encephalopathy.