Hesketh, P.J., Warr, D.G., Street, J.C., & Carides, A.D. (2011). Differential time course of action of 5-HT₃ and NK1 receptor antagonists when used with highly and moderately emetogenic chemotherapy (HEC and MEC). Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer, 19, 1297–1302.

To confirm the differential time course of action noted with a neurokinin 1 (NK1) receptor antagonist (RA) compared to a 5-HT₃ RA in the setting of cisplatin-based chemotherapy using the database from three large, phase III trials

Multivariate logistic regression models were used to assess the impact of the first emesis at different time intervals of aprepitant regimens compared to control regimens using a modified intent-to-treat approach. The endpoint was the frequency of first emesis during distinct time intervals from administration of chemotherapy through 120 hours postadministration.

The trials reported on a total of 2,383 patients.

The mean age range of patients was 52–59 years.

• In the Aprepitant group, the mean age of patients in study 1 was 56 years, the mean age of patients in study 2 was 59 years, and the mean age of patients in study 3 was 53 years.
• In the Control group, the mean age of patients in study 1 was 56 years, the mean age of patients in study 2 was 59 years, and the mean age of patients in study 3 was 52 years.

The percentage of the sample that was male was not reported but assumed to range from 0%–65%. The percentage of females ranged from 35%–100%.

• In the Aprepitant group, study 1 was 42% female, study 2 was 39% female, and study 3 was 99.5% female.
• In the Control group, study 1 was 43% female, study 2 was 35% female, and study 3 was 100% female.

In study 1 and study 2, primary cancer diagnoses were respiratory, urogenital, digestive, and other. In study 3, primary diagnosis was breast cancer.

The majority (59%–80%) were Caucasian.

A total of 1,527 patients were receiving cisplatin-based HEC and 856 were receiving anthracycline plus cyclophosphamide-based moderately emetogenic chemotherapy (MEC).

All patients were in active treatment.

This was a post-hoc analysis.

Measurement instruments and methods were not specified in this article.

With cisplatin-based, highly emetogenic chemotherapy (HEC), the aprepitant regimen was associated with a lower incidence of first vomiting compared to the standard regimen beginning at the 15–18 hour interval and beyond. This lowered incidence was maintained until the 48–60 hour interval, with the first vomiting incidence reduced by 38%–77%.

With anthracycline-cyclophosphamide-based MEC, the first vomiting incidence was markedly lower, as early as the 3–6 hour interval. This effect was maintained up to the 9–12 hour interval, with the first vomiting incidence reduced by 38%–61%.

Emesis induced by cisplatin is biphasic with the initial peak within 2 hours of cisplatin and the second peak starting 16–18 hours and lasting 48 hours after cisplatin. 5-HT₃ medications appear to be most effective in the first 12 hours after cisplatin while NK1-sensitive mechanisms appear to be more effective up to 60 hours after cisplatin.

Anthracycline and cyclophosphamide agents display a monophasic emesis pattern; therefore, better emetic control is noted with NK1-dependent medications much earlier in the treatment cycle.

No discussion was included on how data was collected within each study.

Cisplatin-based regimens require 5-HT₃-dependent medications within the first 12 hours and NK1-dependent medications thereafter.  Anthracycline- and cyclophosphamide-based regimens appear to be sensitive to both 5-HT₃- and NK1-dependent medications.