A phase I and pharmacokinetic trial of terephthalamidine (NSC 57155) as a 120-hour continuous infusion

Gladys I. Rodriguez, John G. Kuhn, Geoffrey Weiss, Pearl De La Cruz, Pamela New, Suzanne M. Fields, John R. Eckardt, Liz Campbell, Gary M. Clark, Susan G. Hilsenbeck, Daniel D. Von Hoff

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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 l/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 l/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.

Original languageEnglish (US)
Pages (from-to)57-67
Number of pages11
JournalInvestigational New Drugs
Issue number1
StatePublished - 1998


  • NSC 57155
  • Pharmacokinetics
  • Phase I
  • Phthalanilides
  • Terephthalamidine

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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