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

Abstract

The aim of the present study was to clarify whether gastric antisecretory drugs affect the clinical efficacy and toxicity of orally administered melphalan in patients with multiple myeloma. A total of 10 patients receiving bortezomib plus oral melphalan and prednisolone (VMP) therapy between December 2011 and November 2014 were analyzed retrospectively. The patients were divided into a control group (seven patients) and a concomitant group (three patients, who were also administered with gastric antisecretory drugs). The gastric antisecretory drugs included rabeprazole sodium (two patients) and famotidine (one patient). No significant differences between the groups were observed in either the characteristics of the patients or the VMP regimen. The levels of monoclonal protein (M protein) in the control group tended to decrease (with a VMP cycle-dependency), although they were primarily stable in the concomitant group. During the second and third VMP cycles, the levels of M protein were markedly lower in the control group compared with the concomitant group. All the patients in the control group achieved a partial response, whereas those in the concomitant group exhibited stable disease. Hematological toxicity levels were revealed to be comparable between the two groups, whereas gastrointestinal toxicity was more prevalent in the control group. In conclusion, the results of the present study suggested that the clinical efficacy of melphalan may be reduced by the co-administration of gastric antisecretory drugs. This interaction may result in decreased toxicity and clinical efficacy of melphalan.

Clinical pharmacokinetics of oral drugs in the treatment of multiple myeloma

“…The decrease in absorption may be related to the decrease in melphalan solubility with increasing pH. In a recent clinical study without pharmacokinetic end point, the administration of melphalan with antisecretory drugs as part of a VMP regimen was associated to a marked decrease in the clinical efficacy of melphalan . As a whole, these studies suggest that melphalan should not be taken concomitantly with antisecretory drugs that have a long duration of action (anti‐H2 and PPI).…”