Correlation between low-dose cyclophosphamide-induced hyponatraemia and the use of aprepitant

e19546 Background: For prevention of nausea/vomiting during anthracyline/cyclophosphamide (CPA) therapy for breast cancer, use of aprepitant (AP) combined with serotonin antagonist and dexamethasone is recommended. It has been reported that AP does not influence AUC’s of 4-hydro-cyclophosphamide, an active metabolite of CPA, and DCE, a CPA-metabolite causing nephrotoxicity. Although, in the previous clinical reports for anthracyline/CPA, the toxicities were not significant in patients who were given AP, compared to those without AP, we have experienced several cases of severe hyponatremia probably caused by AP. Occurrence of hyponatremia during chemotherapy might be an issue to be cautious. Methods: We investigated serum levels of Na in 67 breast cancer patients who received CPA-combined therapy with the use of AP, or not. They all received 600mg/m2 of CPA combined with either of doxorubicine, epirubicin, or docetaxel. Their prior electrolytes were to be within normal range. In the first cycle, we evaluated serum Na levels before the CPA start and those of 24 hours after. We defined a serum Na level lower than 135 mEq/L as “hyponatremia”. Results: The background between the two groups, with AP and without AP, were comparable, in whom the prior Na levels were 140.0 ±1.97 mEq/L, and 140.1 ±1.88 mEq/L, in the AP- and in non-AP-group, respectively. The chemotherapies including CPA, the clinical stages, the uses of serotonin-receptor antagonist and dexamethasone were comparable between the two groups. Hyponatremia occurred in 11 patients out of 42 (26.2%) in AP-group, whereas 2 patients in 25 (8.0%) in non-AP-group. Since the rate in non-AP-group was comparable to the previous reports, hyponetremia seemed to occur frequently in AP-group. The average Na level at 24 hours after chemotherapy was 136.429 ±3.94 mEq/L in AP-group, and 138.68 ±3.05 mEq/L in non-AP-group, respectively. Among 11 patients who developed hyponateremia, they were resolved within 48 hours without any treatments in 10 patients, and only one needed Na replacement. The patient did not develop hyponatremia without using AP in the third cycle. Conclusions: According to our cohort study, AP might frequently cause hyponatremia in the CPA-combined chemotherapy.