Phase I trial of dihydrolenperone in lung cancer patients: A novel compound with in vitro activity against lung cancer

Bruce E. Johnson, Robert Parker, C. M. Tsai, Julie Baltz, Mae Jean Miller, Robert Shoemaker, Ruby Phelps, Anne Bastian, Joyce Stocker, John Phares, James L. Mulshine, Adi F. Gazdar, Daniel C. Ihde

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Antitumor activity of the butyrophenone dihydrolenperone in non-small cell lung cancer was initially suggested by in vitro screening against tumor cells derived from fresh surgical samples using the human tumor colony-forming assay. We have completed a directed phase I trial in patients with lung cancer. Thirty-two patients with lung cancer have completed 25 courses of therapy at doses of 10 to 60 mg/square meter orally on a twice daily schedule. Twenty-three men and 9 women with a median age of 55 (range 24-69) were entered. Twenty-four were performance status 0 or 1 and 8 were 2. The maximum tolerated dose was 50 mg/square meter orally twice daily and the dose limiting toxicity was somnolence. Of the 32 patients, 18 developed symptomatic hypotension (grade 1 or 2). There was no significant hematologic, renal, or hepatic toxicity. In vitro drug testing using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (thiazolyl blue)] assay confirmed 50% inhibition of non-small cell and small cell lung cancer cell line growth at 70-450 micromolar concentrations. Plasma dihydrolenperone levels were at least 75-fold less than levels at which in vitro activity was observed. We conclude: 1) the maximum tolerated dose in our study is 50 mg/square meter orally twice daily, 2) the dose-limiting side effect of dihydrolenperone is somnolence, and 3) the concentrations of dihydrolenperone observed in plasma are significantly lower than those associated with in vitro activity.

Original languageEnglish (US)
Pages (from-to)29-37
Number of pages9
JournalInvestigational New Drugs
Issue number1
StatePublished - Feb 1993


  • antitumor
  • carcinoma
  • dihydrolenperone
  • drug evaluation
  • drug screening assays
  • non-small cell lung carcinoma
  • oat cell

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)


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