Back to Search
Start Over
Phase I trial of dihydrolenperone in lung cancer patients: a novel compound with in vitro activity against lung cancer.
- Source :
-
Investigational new drugs [Invest New Drugs] 1993 Feb; Vol. 11 (1), pp. 29-37. - Publication Year :
- 1993
-
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.
- Subjects :
- Adult
Aged
Antineoplastic Agents adverse effects
Antineoplastic Agents blood
Butyrophenones adverse effects
Butyrophenones blood
Chromatography, High Pressure Liquid
Drugs, Investigational adverse effects
Female
Humans
Male
Middle Aged
Tumor Cells, Cultured
Antineoplastic Agents therapeutic use
Butyrophenones therapeutic use
Drugs, Investigational therapeutic use
Haloperidol therapeutic use
Lung Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0167-6997
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Investigational new drugs
- Publication Type :
- Academic Journal
- Accession number :
- 8349433
- Full Text :
- https://doi.org/10.1007/BF00873907