ORAL GRANISETRON WITH OR WITHOUT METHYLPREDNISOLONE VERSUS METOCLOPRAMIDE PLUS METHYLPREDNISOLONE IN THE MANAGEMENT OF DELAYED NAUSEA AND VOMITING INDUCED BY CISPLATIN-BASED CHEMOTHERAPY - A PROSPECTIVE RANDOMIZED TRIAL

Background. A single-institution, randomized open trial was prospectiv ely performed to compare orally administered granisetron with or witho ut intramuscularly administered methylprednisolone to metoclopramide p lus methylprednisolone in the prevention of delayed nausea and vomitin g induced by cisplatin-based chemotherapy, The effects of antiemetic t reatments were evaluated from days 2 to 5 of the first cycle after cis platin administration among patients who had never before received che motherapy. Methods. All patients were treated with chemotherapeutic re gimens containing cisplatin greater than or equal to 80 mg/m(2) and re ceived antiemetic therapy with granisetron 3 mg intravenously for the control of acute emesis. Patients who responded to treatment during th e first 24 hours were randomized to receive (1) metoclopramide (0.5 mg /kg) intramuscularly three times daily plus methylprednisolone (125 mg ) intramuscularly once a day or (2) granisetron (1 mg) orally twice da ily or (3) oral granisetron (1 mg) orally plus methylprednisolone (125 mg) intramuscularly from days 2 to 5, Results. Of the patients treate d with metoclopramide plus methylprednisolone (n = 92), 53% had comple te protection from delayed emesis, 16% a major response, 15% a minor r esponse, and 15% no response, Of the patients treated with granisetron alone (n = 84), 33% had a complete response, 21% a major response, 23 % a minor response, and 21% no response, In the patients treated with orally administered granisetron plus intramuscularly administered meth ylprednisolone (n = 86), 47% had a complete response, 17% a major resp onse, 23% a minor response, and 13% no response, These differences rea ched statistical significance only when the complete response rate ach ieved in the metoclopramide plus methylprednisolone group was compared with that recorded in the oral granisetron group (P = 0.012). Moreove r, the metoclopramide plus methylprednisolone and the orally administe red granisetron plus corticosteroid arms were superior to the orally a dministered granisetron alone arm in preventing nausea (P < 0.038 and P < 0.002, respectively), No extrapyramidal side effects were noted fo r the granisetron alone and the granisetron plus methylprednisolone ar ms, whereas 6% of patients treated with metoclopramide had extrapyrami dal adverse effects, Headache was recorded in 8% of patients treated w ith granisetron alone, in 9% treated with granisetron plus methylpredn isolone, and in 3% treated with metoclopramide plus methylprednisolone . Conclusions. These data suggest that orally administered granisetron with or without methylprednisolone may be given safely to patients wi th cancer as prophylactic therapy against delayed emesis after high do se cisplatin therapy, Orally administered granisetron alone was less a ctive than a standard combination of metoclopramide plus methylprednis olone. However, the addition of corticosteroid to orally administered granisetron improved the control of delayed emesis. The efficacy of th e combination of metoclopramide plus methylprednisolone and oral grani setron with or without methylprednisolone against delayed emesis still is not entirely satisfactory.