Abstract |
Carbetimer, a new synthetic low molecular weight polyelectrolyte with a novel structure displayed antitumor activity in a number of animal tumor model systems and in vitro investigations. Based on these findings it was brought to a phase I clinical trial in patients with advanced malignant disease after failure of conventional treatment or with no conventional treatment available. Forty-eight patients received 98 courses. The schedule was a one hour i.v. infusion every four weeks. The starting dose was 180 mg/m2 and dose escalation was performed according to a modified Fibonacci formula up to 16,690 mg/m2. At least three patients were treated at each dose level and each patient was eligible to receive repeat courses at the same dose, until progressive disease or dose-limiting toxicity intervened. No hematological toxicity was encountered. Some adverse effects such as reversible proteinuria, hypercalcaemia, pain at infusion site, nausea and vomiting and fatigue were seen partly in a dose-related manner but did not represent the maximum tolerated dose (MTD). The limiting toxicity at the highest dose level of 16,690 mg/m2 consisted of ocular symptoms ('light flashes') accompanied by a modest decrease of blood pressure and nausea or vomiting during a one hour infusion. 16,690 mg/m2/1 hour was considered the MTD. There were four deaths on study, all considered disease-related. Fourteen patients had stable disease for more than two courses, which, however, could also be explained by the natural course of disease. No clear-cut antitumor responses were noted in our study center. The recommended dose for phase II trials derived from our results is 12,550 mg/m2/2 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
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Authors | M Fromm, W E Berdel, H D Schick, S Danhauser-Riedl, U Fink, W Remy, A Reichert, A Ankele, H W Präuer, J R Siewert |
Journal | Investigational new drugs
(Invest New Drugs)
Vol. 6
Issue 3
Pg. 189-94
(Sep 1988)
ISSN: 0167-6997 [Print] United States |
PMID | 3192384
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Polymers
- carboxyimamidate
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Topics |
- Adolescent
- Adult
- Aged
- Antineoplastic Agents
(administration & dosage, adverse effects, therapeutic use)
- Dose-Response Relationship, Drug
- Drug Evaluation
- Female
- Humans
- Infusions, Intravenous
- Male
- Middle Aged
- Polymers
(administration & dosage, adverse effects, therapeutic use)
- Time Factors
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