Methodology of Antiemetic Trials: Response Assessment, Evaluation of New Agents, and Definition of Chemotherapy Emetogenicity

Abstract

Establishing appropriate and practical methodology is a key to progress in the investigation of chemotherapy-induced nausea and vomiting. Critical issues include patient response assessment, proper trial design for evaluating new agents, and the definition of chemotherapy emetogenicity. In assessing antiemetic response, the primary end-point should be complete control of emesis and nausea. Emesis and nausea should be independently assessed with the period of observation defined (acute, delayed, anticipatory). Emesis can be evaluated by measuring the number of emetic episodes either by direct observation or by patient self-report using patient-completed diaries. Nausea should be measured by patient self-report with the standard parameters, including frequency and intensity. New antiemetic drug development should proceed in an orderly progression from open-label phase I/II trials defining tolerance and minimally fully effective dose to phase III comparative trials. A randomized, parallel, double-blind study is the preferred design for the latter, and the comparator arm should always include the current best available treatment. Antiemetic placebos are no longer acceptable with chemotherapy regimens known to produce emesis in a majority of patients. None of the emetogenic classifications proposed to date adequately accounts for all known important patient- and treatment-related prognostic variables. A modification of a recently reported schema is proposed for use in making antiemetic treatment recommendations and defining the emetogenic challenge in clinical trials.