title: 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.
abstract: BACKGROUND
  A single-institution, randomized open trial was prospectively performed to compare orally administered granisetron with or without intramuscularly administered methylprednisolone to metoclopramide plus methylprednisolone in the prevention of delayed nausea and vomiting induced by cisplatin-based chemotherapy. The effects of antiemetic treatments were evaluated from days 2 to 5 of the first cycle after cisplatin administration among patients who had never before received chemotherapy.
  
  
  METHODS
  All patients were treated with chemotherapeutic regimens containing cisplatin greater than or equal to 80 mg/m2 and received antiemetic therapy with granisetron 3 mg intravenously for the control of acute emesis. Patients who responded to treatment during the 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 daily or (3) oral granisetron (1 mg) orally plus methylprednisolone (125 mg) intramuscularly from days 2 to 5.
  
  
  RESULTS
  Of the patients treated with metoclopramide plus methylprednisolone (n = 92), 53% had complete protection from delayed emesis, 16% a major response, 15% a minor response, 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 methylprednisolone (n = 86), 47% had a complete response, 17% a major response, 23% a minor response, and 13% no response. These differences reached statistical significance only when the complete response rate achieved in the metoclopramide plus methylprednisolone group was compared with that recorded in the oral granisetron group (P = 0.012). Moreover, the metoclopramide plus methylprednisolone and the orally administered granisetron plus corticosteroid arms were superior to the orally administered granisetron alone arm in preventing nausea (P < 0.038 and P < 0.002, respectively). No extrapyramidal side effects were noted for the granisetron alone and the granisetron plus methylprednisolone arms, whereas 6% of patients treated with metoclopramide had extrapyramidal adverse effects. Headache was recorded in 8% of patients treated with granisetron alone, in 9% treated with granisetron plus methylprednisolone, 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 with cancer as prophylactic therapy against delayed emesis after high dose cisplatin therapy. Orally administered granisetron alone was less active than a standard combination of metoclopramide plus methylprednisolone. However, the addition of corticosteroid to orally administered granisetron improved the control of delayed emesis. The efficacy of the combination of metoclopramide plus methylprednisolone and oral granisetron with or without methylprednisolone against delayed emesis still is not entirely satisfactory.
authors.affiliation: Service of Chemotherapy, Institute of Pharmacology, University of Palermo, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Gebbia
authors.forename: A
authors.initials: A
authors.lastname: Testa
authors.forename: R
authors.initials: R
authors.lastname: Valenza
authors.forename: G
authors.initials: G
authors.lastname: Cannata
authors.forename: M L
authors.initials: ML
authors.lastname: Tirrito
authors.forename: N
authors.initials: N
authors.lastname: Gebbia
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000008:administration & dosage*; D002945:Cisplatin / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005260:Female; D017829:Granisetron / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000009:adverse effects; D008787:Metoclopramide / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy*; D011446:Prospective Studies; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D002945:Cisplatin; D017829:Granisetron; D008775:Methylprednisolone; D008787:Metoclopramide