The oral NK1 antagonist, aprepitant, given with standard antiemetics provides protection against nausea and vomiting over multiple cycles of cisplatin-based chemotherapy: a combined analysis of two randomised, placebo-controlled phase III clinical trials

• Published in: European journal of cancer (1990) 2004-02, Vol.40 (3), p.403-410
• Main Authors: de Wit, R., Herrstedt, J., Rapoport, B., Carides, A.D., Guoguang-Ma, J., Elmer, M., Schmidt, C., Evans, J.K., Horgan, K.J.
• Format: Article
• Language: English
• Subjects: Antiemetic; Aprepitant; Biological and medical sciences; Cancer; Medical sciences; Nausea and vomiting; NK1 antagonist; Pharmacology. Drug treatments; Supportive care; Tumors
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2003.08.028

In early clinical trials, the NK1 receptor antagonist, aprepitant (EMEND®) was shown to improve the protection provided by the best available therapy (hereafter referred to as ‘standard therapy’: a 5-HT3 receptor antagonist and dexamethasone) against chemotherapy-induced nausea and vomiting over multiple cycles of cisplatin-based chemotherapy. To further study the sustainment of antiemetic efficacy of aprepitant plus standard therapy over more than one cycle of chemotherapy, we examined combined data from the multiple cycles extensions of two phase III clinical trials of oral aprepitant plus standard therapy for the prevention of chemotherapy-induced nausea and vomiting. Data were pooled from two multicentre, randomised, double-blind, placebo-controlled studies with identical design and treatment regimens. Cancer patients receiving a first cycle of cisplatin-based (⩾70 mg/m2) chemotherapy were randomised to one of two treatment groups as follows: the standard therapy group received ondansetron 32 mg intravenously (i.v.) and dexamethasone 20 mg on day 1 and dexamethasone 8 mg twice daily (b.i.d.) on days 2–4. The aprepitant group received aprepitant 125 mg, ondansetron 32 mg i.v., and dexamethasone 12 mg on day 1, aprepitant 80 mg and dexamethasone 8 mg on days 2–3, and dexamethasone 8 mg on day 4. Patients had the option to receive the same blinded treatment for up to five additional cycles. The analysis used a combined exploratory endpoint of no emesis and no significant nausea (i.e. nausea which interfered with a patient's normal activities) over the 5 days following cisplatin, for up to six cycles of chemotherapy. A cumulative probabilities approach incorporating a model for transitional probabilities was used to analyse the data. Tolerability was assessed by reported adverse events and physical and laboratory assessments. Baseline characteristics, reasons for discontinuation, and drop-out rates were similar between groups. In every cycle, the estimated probabilities (rates) of no emesis and no significant nausea were significantly higher (P