TOTAL-BODY IRRADIATION PRIOR TO BONE-MARROW TRANSPLANTATION - EFFICACY AND SAFETY OF GRANISETRON IN THE PROPHYLAXIS AND CONTROL OF RADIATION-INDUCED EMESIS

Purpose: Radiation-induced emesis is one of the most disturbing side e ffects of total body irradiation (TBI). To evaluate the efficacy and t o determine the best schedule of granisetron (a selective-5-hydroxytry ptamine-3 serotonin receptor antagonist) administration in the prevent ion of radiation-induced nausea and vomiting, we conducted a trial inv olving patients receiving single-dose TBI before bone marrow transplan tation (BMT). Methods and Materials: Thirty-six patients with non-Hodg kin's lymphoma (n = 12), multiple myeloma (n = 8), acute lymphoblastic leukemia (n = 7), acute nonlymphoblastic leukemia (n = 6), and chroni c myeloid leukemia (n = 3) referred to our department between March 19 92 and February 1991 were enrolled in this study to assess the efficac y of granisetron during single-dose TBI before autologous BMT (12 = 26 ), allogeneic BMT (n = 8), or syngeneic BMT (n = 2). The male-to-femal e ratio was 22:14 (1.57), and the mean age was 41 +/- 11 years (range 16-58). Before TBI, conditioning chemotherapy consisted of cyclophosph amide (CY) alone (60 mg/kg per day on 2 successive days) in 24 patient s, CY combined with other drugs in 6, and combinations without CY in 6 . All patients received single-dose TBI (10 Gy administered to the mid plane at L4, and 8 Gy to the lungs). The mean instantaneous and averag e dose rates were 0.039 +/- 0.012 Gy/min (range 0.031-0.058), and 0.02 5-0.006 Gy/min (range 2.08-3.96), respectively. Granisetron was admini stered 30-45 min before TBI according to two different modalities: a t otal dose of 3 mg as a 5-min intravenous (i.v.) infusion (Treatment A, n = 15; 42%) or the same treatment plus 3 mg of granisetron as a 24-h continuous i.v. infusion (total dose: 6 mg, Treatment B, n = 21; 58%) . Depending on the BMT teams, hyperdiuresis was continued (12 = 19, 53 %) or suspended (n = 17, 47%) during TBI. Nausea and vomiting were ass essed during the TBI session and the following 12 h, and were scored a s follows: S1 = no nausea or vomiting; S2 = moderate nausea; S3 = seve re nausea and/or single episode of vomiting; and S4 = multiple episode s of vomiting. Results: During TBI, 18 (50%) patients were scored as c omplete responders (S1), 1 (3%) as a major responder (S2), 9 (25%) as minor responders (S3), and 8 (22%) as nonresponders (S4). During the f ollowing 12 h, 28 (78%) patients were free of severe nausea and vomiti ng (S1 or S2), whereas 8 (22%) vomited (S3 or S4). In univariate analy ses, the 12-h probability of emesis was significantly higher in patien ts undergoing hyperdiuresis (63% vs. 30%; p = 0.05), and in patients o lder than 45 Sears (65% for age >45 vs. 33% for age less than or equal to 45; p = 0.05). The probability of S3 or S4 emesis was 50% with Tre atment A and 47% with Treatment B (p = 0.86). Sex, body weight, and ty pe of conditioning chemotherapy did not influence the 12-h probability of emesis. Multivariate analysis revealed that hyperdiuresis (p = 0.0 2) and Treatment A (p = 0.01) were independently associated with radia tion-induced emesis, whereas sex (p = 0.85), body weight (p = 0.13), a ge (p = 0.12), and type of conditioning chemotherapy (p = 0.92) were n ot. No early toxicity related to granisetron was observed. Conclusion: Granisetron is a well-tolerated and effective antiemetic agent that c an be used as monotherapy during single-dose TBI. Good control of naus ea and vomiting is obtained with this antiemetic drug, and its effect is increased when hyperdiuresis is suspended during TBI.