title: A phase I and pharmacokinetic trial of terephthalamidine (NSC 57155) as a 120-hour continuous infusion.
abstract: In this phase I study, terephthalamidine was administered as a 120-hour continuous infusion repeated every 21 days. Thirteen patients received 27 courses of terephthalamidine at four dose levels ( 14, 28, 46, and 70 mg/m2/day). Dose-limiting toxicity consisted of profound and intractable anorexia, weight loss and prostration in all patients. Toxicity was delayed and accompanied by hyponatremia and hypokalemia. No hematologic or other toxicity was documented. One patient with adenocarcinoma of the lung had a 40% decrease in mediastinal lymph nodes and resolution of a pleural effusion lasting 2 months. Pharmacokinetic analysis by HPLC was performed in all patients during their first course. The harmonic mean terminal half-life for terephthalamidine was 23 hours with a plasma clearance of 1.7 1/hr/m2. Both plasma concentrations achieved during infusion (r2 = 0.9) and area under the curve (AUC) (r2 = 0.8) were proportional to increase in dose (p < 0.002). Renal excretion accounted for 64% of the total cumulative dose, with an average renal clearance of 1.16 1/hr/m2. Due to the unacceptable toxicity seen at all doses with this schedule, no further studies are recommended unless the mechanism of toxicity is better understood and can be prevented.
authors.affiliation: The University of Texas Health Science Center at San Antonio, 78284-6220, USA.
authors.forename: G I
authors.initials: GI
authors.lastname: Rodriguez
authors.forename: J G
authors.initials: JG
authors.lastname: Kuhn
authors.forename: G
authors.initials: G
authors.lastname: Weiss
authors.forename: P
authors.initials: P
authors.lastname: De La Cruz
authors.forename: P
authors.initials: P
authors.lastname: New
authors.forename: S M
authors.initials: SM
authors.lastname: Fields
authors.forename: J R
authors.initials: JR
authors.lastname: Eckardt
authors.forename: L
authors.initials: L
authors.lastname: Campbell
authors.forename: G M
authors.initials: GM
authors.lastname: Clark
authors.forename: S G
authors.initials: SG
authors.lastname: Hilsenbeck
authors.forename: D D
authors.initials: DD
authors.lastname: Von Hoff
mesh_terms: D000328:Adult; D000368:Aged; D000855:Anorexia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D001835:Body Weight / Q000187:drug effects; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010797:Phthalimides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D015431:Weight Loss
chemical_list: D000970:Antineoplastic Agents; D010797:Phthalimides; C047750:terephthalamidine