1578P - Correlation between cyclophosphamide-induced hyponatraemia and the use of aprepitant

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Complications/Toxicities of Treatment
Presenter Yasutaka Tono
Authors Y. Tono, T. Mizuno, K. Saito, S. Tamaru, Y. Yamashita, H. Oda, S. Kageyama, N. Katayama
  • Medical Oncology, Mie University Hospital, 514-8507 - Tsu/JP



For prevention of emesis during anthracyline (A)/cyclophosphamide(CPA) therapy for breast cancer, use of aprepitant(AP) combined with serotonin receptor antagonist(5HT3) and dexamethasone(DEX) is recommended. AP, known to function as a CYP3A4 inhibitor, has been reported to interfere with metabolism of chemotherapeutic drugs. It has been also reported that AP does not influence the AUC's of 4-OH and DCE. Although, in the previous clinical reports for AC, the toxicities were not significant in patients who were given AP, compared to those without AP, we have experienced a cases of severe hyponatremia probably related to AP. Thus, we investigated an impact of AP on Na metabolism during chemotherapy using CPA for breast cancer.

Material and methods

We investigated serum levels of Na in primary breast cancer patients who received CPA-combined therapy with the use of AP as anti-emesis, or not. They all received 600mg/m2 of CPA combined with either of anthracycline or docetaxel. Their ages were to be less than 65 years, and their GFR's were more than 60 ml/min/1.73m2. Their prior electrolytes were to be within normal range. In the first cycle, we evaluated serum Na levels before the CPA start and that at 24 hours after. We defined serum Na level lower than 135 mEq/L as “hyponatremia” based on previous study. We enrolled 81 patients, in whom 52 were given AP and 29 were without AP, between December 2010 and April 2012.


The background between the two groups, with AP and without AP, were comparable, in whom the median ages were 53.0(33-64) and 53.2(38-65), and the prior Na levels were139.84 ± 1.89 mEq/L, and 140.25 ± 1.82 mEq/L, in the AP-group and in non-AP-group, respectively. The uses of 5HT3 and DEX were similar between the two groups. The incidence of CPA-induced hyponatremia was significantly higher in AP-group than in non-AP-group (26.9% v 6.9%; P =0.04). The average Na level at 24 hours after chemotherapy was 136.32 ± 3.73 mEq/L in AP-group, and 138.60 ± 2.92 mEq/L in non-AP-group. Among 14 patients who developed hyponateremia in AP-group, they were resolved without any intervention in 13, and one needed Na replacement. The patient did not develop hyponatremia without AP in the third cycle.


According to our cohort study, AP cause hyponatremia more frequently in the CPA-combined chemotherapy.


All authors have declared no conflicts of interest.