| Autor: |
Eccles, Diana M., Cummings, Jeffrey, Stewart, Moira E., Nicolson, Margaret, Cornbleet, Michael A., Leonard, Robert C. F., Smyth, John F. |
| Zdroj: |
Cancer Chemotherapy and Pharmacology; September 1992, Vol. 29 Issue: 5 p375-378, 4p |
| Abstrakt: |
GR63178A is a water-soluble analogue of mitoquidone, a pentacyclic pyrroloquinone. This group of drugs exhibit a novel structure and activity against several murine solid tumours and xenografts. In the present phase I study the toxicity and pharmacokinetics of GR63178A given on 5 consecutive days of a 21-day cycle were examined. A total of 24 patients presenting with a wide range of tumours were treated at 5 doses escalated to reach the maximal tolerated dose (MTD). Linear pharmacokinetics was documented over the dose range studied, and there was no difference in parent drug handling between day 1 and day 4 of dosing. A number of metabolites were detected. The toxicity profile was unusual in that pain occurred in 20/24 patients, most often at the site of known disease. This was the dose-limiting toxicity. Other side effects included nausea and vomiting (23/24), phlebitis at the infusion site (6/24) and headache (7/24). No treatment response was seen in this study. The MTD was demonstrated to be 160 mg/m2 daily (total, 800 mg/m2 per treatment cycle). the drug has now entered phase II trials at 120 mg/m2 daily x 5, repeated every 21 days. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Full text from SpringerLink