DOUBLE-BLIND, MULTICENTER, RANDOMIZED TRIAL TO COMPARE THE EFFECT OF 2 DOSES OF ADRENOCORTICOTROPIC HORMONE VERSUS PLACEBO IN CONTROLLING DELAYED EMESIS AFTER HIGH-DOSE CISPLATIN IN ADULT PATIENTS WITH CANCER

Purpose: To compare, in a double-blind, placebo-controlled, randomized trial, the efficacy of two different doses of the depot formulation o f adrenocorticotropic hormone (ACTH) in controlling delayed emesis aft er cisplatin. Patients and Methods: One hundred fifty-two patients wer e enrolled onto the study. On day 1, all patients received cisplatin ( 60 to 120 mg/m(2)) and a combination of dexamethasone 20 mg plus ondan setron or metoclopramide to prevent acute emesis, On day 2 (24 hours a fter cisplatin administration), patients were random ized to receive p lacebo, or ACTH 1 mg intramuscularly (IM), or ACTH 2 mg IM plus one ad ditional dose of 1 mg on day 4. Details of vomiting, nausea, and adver se effects were recorded daily for every 24-hour period from day 2 to day 6, In a subset of patients, serum cortisol levels were measured be tween 20 and 72 hours after cisplatin administration. Results: One hun dred fifty patients were assessable, Over the 5 days of the study, del ayed vomiting occurred less frequently in the patients treated with AC TH 2 mg plus 1 mg than in those treated with ACTH 1 mg or placebo (28% , 38%, and 65%, respectively; P = .001). The greatest observed differe nces were seen on days 2 (24 to 48 hours; P = .01) and 3 (48 to 72 hou rs; P = .01). On days 4, 5, and 6 (96 to 144 hours), no significant di fferences were observed among the three arms. The severity of delayed emesis expressed as the mean number of emetic episodes per day was 0.4 8, 0.70, and 0.80, respectively (P = .002). Patients treated with the higher dose of ACTH had the least nausea on day 3 (P = .02) and day 4 (P = .03). Adrenal cortisol secretion rapidly increased after ACTH inj ection, but was suppressed for approximately 44 hours in the placebo g roup. Toxicity was mild and transient in all groups, Conclusion: ACTH reduces the incidence and severity of-belayed vomiting and nausea afte r cisplatin. A dose of 2 mg 24 hours after cisplatin is better than on e of 1 mg. Whether the activity of ACTH is mediated only by adrenal co rticosteroids needs to be verified, (C) 1997 by American Society of Cl inical Oncology.