Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Eckel, F; Schmelz, R; Adelsberger, H; Erdmann, J; Quasthoff, S; Lersch, C.
Prevention of oxaliplatin-induced neuropathy by carbamazepine. A pilot study
DEUT MED WOCHENSCHR 2002 127: 78-82.
Doi: 10.1055/s-2002-19594
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Quasthoff Stefan
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- Abstract:
- INTRODUCTION: Oxaliplatin has been proven antitumoral activity in numerous clinical trials. Peripheral sensory neuropathy with predominantly hyperpathic symptoms induced by cold is the most severe and dose-limiting toxicity resulting from oxaliplatin therapy. We demonstrated that oxaliplatin alters sodium channel kinetics on sensory neurons. This effect could be antagonized in vitro by the sodium channel blocker carbamazepine. Therefore a pilot study was initiated to investigate if carbamazepine prevents oxaliplatin-induced neuropathy in patients with colorectal cancer. PATIENTS AND METHODS: Ten patients (six males, four females, mean age 56 +/- 12 years) refractory to 5-fluorouracil were treated with oxaliplatin, 5-fluorouracil, and folinic acid. The patients additionally received carbamazepine. Doses were adapted to a serum level of 3 - 6 mg/l. Patients were questioned about side-effects weekly and treatment-related toxicities were documented using the modified WHO scale. Results were compared with 30 historic controls treated with the same chemotherapy without carbamazepine. RESULTS: The cumulative oxaliplatin dose was higher in the carbamazepine group (median 722 mg/m(2) and 510 mg/m(2), respectively, p = 0.020). Carbamazepine levels were 4.5 +/- 1.5 mg/l. In contrast to the control group no neuropathy higher than grade 1 occurred in the carbamazepine group. Rate of carbamazepine-induced side effects was low. CONCLUSIONS: These observations demonstrate that oxaliplatin-induced sensory neuropathy more than grade 1 may be prevented by carbamazepine. Prevention of oxaliplatin-induced neurotoxicity by carbamazepine would possibly enable chemotherapy with considerable higher doses of oxapliplatin and thus enhance activity. A multicenter trial will elucidate if more serious distal neurotoxicities, which occur after application of higher cumulative doses of oxaliplatin, can also be prevented by carbamazepine.
- Find related publications in this database (using NLM MeSH Indexing)
- Antimetabolites, Antineoplastic - administration and dosage
- Antineoplastic Agents - administration and dosage
- Antineoplastic Combined Chemotherapy Protocols - adverse effects
- Carbamazepine - adverse effects
- Colorectal Neoplasms - drug therapy
- Female - drug therapy
- Fluorouracil - administration and dosage
- Humans - administration and dosage
- Leucovorin - administration and dosage
- Male - administration and dosage
- Middle Aged - administration and dosage
- Organoplatinum Compounds - administration and dosage
- Peripheral Nervous System Diseases - chemically induced
- Pilot Projects - chemically induced
- Treatment Outcome - chemically induced