Co-administration of mesna with doxorubicin-containing chemotherapy reduced post-treatment levels of TNF-receptor 1 and TNF-receptor 2 (p=0.05 and p=0.002, respectively) compared to saline.
RCT (n=32)
Double-blind
Stratified block randomization
No
p-value: p=0.05 and 0.002
PURPOSE: Chemotherapy-induced cognitive impairment (CICI) is a common sequelae of cancer therapy. Recent preclinical observations have suggested that CICI can be mediated by chemotherapy-induced plasma protein oxidation, which triggers TNF-α mediated CNS damage. This study evaluated sodium-2-mercaptoethane sulfonate (Mesna) co-administration with doxorubicin to reduce doxorubicin-induced plasma protein oxidation and resultant cascade of TNF-α, soluble TNF receptor levels and related cytokines. METHODS: Thirty-two evaluable patients were randomized using a crossover design to receive mesna or saline in either the first or second cycle of doxorubicin in the context of a standard chemotherapy regimen for either non-Hodgkin lymphoma or breast cancer. Mesna (360 mg/m2) or saline administration occurred 15 minutes prior and three hours post doxorubicin. Pre-treatment and post-treatment measurements of oxidative stress, TNF-α and related cytokines were evaluated during the two experimental cycles of chemotherapy. RESULTS: Co-administration of mesna with chemotherapy reduced post-treatment levels of TNF-related cytokines and TNF-receptor 1 (TNFR1) and TNF-receptor 2 (TNFR2) (p = 0.05 and p = 0.002, respectively). Patients with the highest pre-treatment levels of each cytokine and its receptors were the most likely to benefit from mesna co-administration. CONCLUSIONS: The extracellular anti-oxidant mesna, when co-administered during a single cycle of doxorubicin, reduced levels of TNF-α and its receptors after that cycle of therapy, demonstrating for the first time a clinical interaction between mesna and doxorubicin, drugs often coincidentally co-administered in multi-agent regimens. These findings support further investigation to determine whether rationally-timed mesna co-administration with redox active chemotherapy may prevent or reduce the cascade of events that lead to CICI. TRIAL REGISTRATION: clinicaltrials.gov NCT01205503.
Hayslip et al. (Fri,) conducted a rct in Breast cancer or non-Hodgkin lymphoma (n=32). Mesna vs. Saline was evaluated on Plasma TNF-α, TNFR1, TNFR2, IL-18, and plasma protein oxidation levels (p=0.05 and 0.002). Co-administration of mesna with doxorubicin-containing chemotherapy reduced post-treatment levels of TNF-receptor 1 and TNF-receptor 2 (p=0.05 and p=0.002, respectively) compared to saline.