title: A dose finding study of prochlorperazine as an antiemetic for cancer chemotherapy.
abstract: This phase I study determined the maximum tolerated dose of prochlorperazine when used as an antiemetic prior to cytotoxic chemotherapy. Initially, cohorts of three patients were given prochlorperazine at escalating doses of 0.2, 0.4, 0.6, 0.8, 1.0 and 1.2 mg/kg as an intravenous infusion over 20 min. The maximum tolerated dose was 1.2 mg/kg. The dose-limiting toxicity was hypotension which was reversed by a fluid load. The other major toxicities were extrapyramidal reactions which were dose related. All patients at the 1.2 mg/kg dose reported restlessness while five of six were restless and two of six at 1.0 mg/kg had muscle spasms. Two of seven patients reported restlessness at the 0.8 mg/kg level. Sedation and dry mouth were reported at all dose levels but were more common at higher doses. Prochlorperazine in plasma was assayed by high performance liquid chromatography with electrochemical detection and pharmacokinetics were determined for three patients at the 1.0 mg/kg dose level. The average terminal elimination half life was 7.6 +/- 0.4 h, plasma clearance 27 +/- 5 ml/min/kg and volume of distribution 17.7 +/- 4.5 l/kg. The dose of prochlorperazine recommended for further studies of antiemetic efficacy is 0.8 mg/kg intravenously.
authors.affiliation: Department of Cancer Medicine, Peter MacCallum Cancer Institute, Melbourne, Australia.
authors.forename: I N
authors.initials: IN
authors.lastname: Olver
authors.forename: L K
authors.initials: LK
authors.lastname: Webster
authors.forename: J F
authors.initials: JF
authors.lastname: Bishop
authors.forename: J
authors.initials: J
authors.lastname: Clarke
authors.forename: B L
authors.initials: BL
authors.lastname: Hillcoat
mesh_terms: D000932:Antiemetics / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D004341:Drug Evaluation; D006801:Humans; D011346:Prochlorperazine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D014839:Vomiting / Q000517:prevention & control
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D011346:Prochlorperazine