The protective effects of lafutidine for bortezomib induced peripheral neuropathy

Abstract

Peripheral neuropathy (PN) caused by bortezomib is an important complication of multiple myeloma. Subcutaneous injection of bortezomib reduced PN, but 24% of cases were grade 2 PN and 6% of cases were grade 3 PN. PN higher than grade 2 was not resolved by subcutaneous injection. PN higher than grade 3 has serious dose limiting toxicity and is the cause of discontinuing bortezomib treatment. Lafutidine is an H2-blocker with gastroprotective activity and is thought to function by increasing mucosal blood flow via capsaicin sensitive neurons. The same activity of lafutidine is considered to improve glossodynia and taxane induced PN. We hypothesized that lafutidine prevents or improves PN that is caused by bortezomib. In the current study, bortezomib was administered in the usual manner (intravenous administration of bortezomib 1.3 mg/m2, twice a week for 2 weeks, followed by 1 week without treatment) for up to four cycles to compare our data with other studies. Lafutidine was administered orally at a dose of 10 mg twice daily. In our eight evaluated cases, the total occurrence of PN was four out of eight patients (50%). There were only grade 1 PN (4 out of 8) cases, and no cases higher than grade 2. We conclude that (1) the total occurrence of PN was not improved, (2) there was no PN after the first course, (3) there were only grade 1 cases and there were no cases higher than grade 2, and (4) no cases discontinued bortezomib treatment because of PN. This is the first report showing that lafutidine is useful for the amelioration of bortezomib induced PN.

An Overview of Bortezomib-Induced Neurotoxicity

“…Meantime, Alè and colleagues demonstrated that monoclonal antibodies directed against TNF-α may be an appropriate neuroprotective therapy against BTZ-induced neurotoxicity [ 62 ]. In addition, based on a small clinical report published by Tsukaguchi et al , lafutidine (a new histamine H2-receptor antagonist) may be able to ameliorate BIPN through the increase of mucosal blood flow via capsaicin sensitive neurons [ 63 ]. Therefore, interventions on BIPN remain merely symptomatic, so the international guidelines focused on the relief of neuropathic pain through the use of tricyclic antidepressants (TCAs), anticonvulsants (as calcium channels α2-δ ligands, i.e.…”

Chemotherapy-induced peripheral neuropathy in the adult

“…For historical reasons, in most clinical trials the occurrence and severity of CIPN are assessed by the United States National Cancer Institute common toxicity criteria (NCI-CTC) scales despite notable interobserver disagreement in clinical studies of anticancer treatments [18] or neuroprotective strategies [19][20][21][22][23][24][25] …”

“…Lafutidine, an H2 blocker with gastroprotective activity may be able to prevent or improve bortezomib-induced peripheral neuropathy on the basis of the results of a recently published small case series of eight patients [22]. However, the protective activity of lafutidine against bortezomib-induced peripheral neuropathy needs to be further demonstrated.…”

The interaction between oral melphalan and gastric antisecretory drugs: Impact on clinical efficacy and toxicity

“…Taken together, these findings suggested that the clinical efficacy of the VMP regimen against MM decreases on co-administration of the gastric antisecretory drugs. As for bortezomib, the pharmacokinetics, efficacy and safety of bortezomib were not affected by co-administration of either the proton-pump inhibitor, omeprazole (27), or the H 2 receptor blocker, lafutidine (28).…”