Aprepitant--where do we stand in the control of chemotherapy-induced nausea and vomiting?

Despite progress in the area of supportive care in oncology in the last two decades, nausea and vomiting continue to be significant side effects of cancer therapy. These symptoms can escalate over time and can result in patients' refusal to continue with chemotherapy. Introduction of serotonin (5-HT3) receptor antagonists was a major therapeutic advance in the treatment of chemotherapy-induced nausea and vomiting with enhanced efficacy when corticosteroids were added. However, these agents have limited protection in the acute phase of chemotherapy-induced nausea and vomiting with little or no effect over the delayed phase. The aim of this review was to introduce a new class of antiemetics, a selective high-affinity antagonist at human substance P neurokinin 1 (NK(1)) receptors-aprepitant. Its pharmacological characteristics as well as its efficacy are reviewed. Aprepitant appears to be well tolerated but, due to its inhibitory effect on cytochrome P450 isoenzyme 3A4, it can lead to significant drug interactions, resulting in need for dose modification of concomitant therapy. The addition of aprepitant to 5-HT(3) receptor antagonists and corticosteroids was found to be superior to the combination of 5-HT(3) receptor antagonists and corticosteroids alone in patients treated with highly and moderately emetogenic chemotherapy. Clinical trials with aprepitant and other antiemetic agents are warranted to determine a regimen that will ensure complete protection from both acute and delayed chemotherapy-induced nausea and vomiting, thus contributing to improved supportive care and patients' quality of life (QoL).