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

Abstract

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.

• Authors: B E Johnson, R Parker, C M Tsai, J Baltz, M J Miller, R Shoemaker, R Phelps, A Bastian, J Stocker, J Phares
• Journal: Investigational new drugs (Invest New Drugs) Vol. 11 Issue 1 Pg. 29-37 (Feb 1993) ISSN: 0167-6997 [Print] United States
• PMID: 8349433 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Comparative Study, Journal Article)

Chemical References

• Antineoplastic Agents
• Butyrophenones
• Drugs, Investigational
• dihydrolenperone
• Haloperidol

Topics

• Adult
• Aged
• Antineoplastic Agents (adverse effects, blood, therapeutic use)
• Butyrophenones (adverse effects, blood, therapeutic use)
• Chromatography, High Pressure Liquid
• Drugs, Investigational (adverse effects, therapeutic use)
• Female
• Haloperidol (therapeutic use)
• Humans
• Lung Neoplasms (drug therapy)
• Male
• Middle Aged
• Tumor Cells, Cultured