METHODOLOGY OF ANTIEMETIC TRIALS - RESPONSE ASSESSMENT, EVALUATION OFNEW AGENTS AND DEFINITION OF CHEMOTHERAPY EMETOGENICITY

Establishing appropriate and practical methodology is a key to progres s in the investigation of chemotherapy-induced nausea and vomiting. Cr itical issues include patient response assessment, proper trial design for evaluating new agents, and the definition of chemotherapy emetoge nicity. 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 numb er of emetic episodes either by direct observation or by patient self- report using patient-completed diaries. Nausea should be measured by p atient self-report with the standard parameters, including frequency a nd intensity. New antiemetic drug development should proceed in an ord erly 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 t he latter, and the comparator arm should always include the current be st available treatment. Antiemetic placebos are no longer acceptable w ith chemotherapy regimens known to produce emesis in a majority of pat ients, None of the emetogenic classifications proposed to date adequat ely accounts for all known important patient-and treatment-related pro gnostic variables, A modification of a recently reported schema is pro posed for use in making antiemetic treatment recommendations and defin ing the emetogenic challenge in clinical trials.