Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity—an update

Abstract

Development of effective antiemetic therapy depends upon an understanding of both the antiemetic agents and the emetogenic challenges these agents are designed to address. New potential antiemetic agents should be studied in an orderly manner, proceeding from phase I to phase II open-label trials and then to randomized double-blind phase III trials comparing new agents and regimens to best standard therapy. Use of placebos in place of antiemetic therapy against highly or moderately emetogenic chemotherapy is unacceptable. Nausea and vomiting should be evaluated separately and for both the acute and delayed periods. Defining the emetogenicity of new antineoplastic agents is a challenge, since such data are often not reliably recorded during early drug development. A four-level classification system is proposed for emetogenicity of intravenous antineoplastic agents. A separate four-level classification system for emetogenicity of oral antineoplastic agents, which are often given over an extended period of time, is also proposed.

Effect of a Nausea Expectancy Manipulation on Chemotherapy-Induced Nausea: A University of Rochester Cancer Center Community Clinical Oncology Program Study

“…[1][2][3][4][5] Although the occurrence and severity of chemotherapy-induced NV derive largely from the emetogenic potential of the chemotherapeutic drugs, individual patient characteristics, such as younger age, 6 female gender, 7 previous experience of pregnancy-related nausea, 6,8 and a history of motion sickness, 9 play a role. Even taking all these factors into account, there is great deal of variability both across and within specific chemotherapyregimens with respect to the occurrence and severity of NV.…”

Aprepitant: the evidence for its place in the prevention of chemotherapy-induced nausea and vomiting

“…However, some chemotherapy of moderate emetogenic potential has a greater tendency to cause delayed CINV, notably carboplatin, cyclophosphamide, and doxorubicin Markman 2002). Furthermore, although cyclophosphamide and doxorubicin individually are classified as being moderately emetogenic, the likelihood of CINV increases when these agents are combined, as they frequently are in the adjuvant treatment of women with breast cancer (Grunberg et al 2005). As mentioned earlier, particular patient groups, such as women, are at higher risk of CINV.…”

Antiemesis

“…12,[24][25][26][27] Hesketh et al 28 developed a classification of acute emetogenicity for anticancer chemotherapeutic agents and an algorithm to define the emetogenicity of combination chemotherapeutic regimens. The classification, which was updated by Grunberg et al, 29 divides chemotherapeutic agents into 4 levels according to the percentage of patients not receiving antiemetic prophylaxis who experience acute emesis. This classification, which was updated with recently introduced drugs, is used in these guidelines.…”