Peripheral neurotoxicity of taxol in patients previously treated with cisplatin.
BACKGROUND
Taxol is a new anticancer drug that acts as a tubulin polymeration enhancer. Its major toxicities are myelosuppression, hypersensitivity, and mucositis, but it also induces peripheral nerve damage. The use of taxol has recently been proposed for platinum-resistant cancers, but in these cases there is a possibility of cumulative toxicity in the peripheral nervous system.


METHODS
Twenty-two patients affected by a relapse of cisplatin-treated ovarian cancer were examined clinically and neurophysiologically to determine the evolution of taxol-induced peripheral somatic and autonomic neurotoxicity and the possible cumulative effect of a combination of taxol and cisplatin. Each patient was examined before, during, and after taxol treatment (using a dose of 135 or 175 mg/m2 in 3 hours every 3 weeks).


RESULTS
No patients were excluded from the study because of unacceptable toxicities of any kind. The serial examinations demonstrated that taxol induced onset of (or worsening of preexisting) neuropathic symptoms and signs in almost all the patients. The features were those of a distal, symmetrical, sensory polyneuropathy due to an axonopathy. Motor nerves and the autonomic nervous system were unaffected. Taxol neurotoxicity appeared early in the course of the treatment (i.e., after three courses) and was not severely disabling. In most cases after the early onset of peripheral neuropathy, stabilization of this side effect occurred.


CONCLUSIONS
Considering the low doses of taxol used in this study, the sensory nerve damage was unexpectedly severe. It appears that a cumulative, but not dose-limiting, neurotoxic effect occurs using taxol in patients previously treated with cisplatin.
Department of Neurology, S. Gerardo Institute for Biomedical Sciences, University of Milan, Monza, Italy.
G
G
Cavaletti
G
G
Bogliun
L
L
Marzorati
A
A
Zincone
M
M
Marzola
N
N
Colombo
G
G
Tredici
D000328:Adult; D002277:Carcinoma / Q000188:drug therapy / Q000503:physiopathology*; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D017239:Paclitaxel / Q000009:adverse effects* / Q000627:therapeutic use; D010525:Peripheral Nerves / Q000187:drug effects* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000503:physiopathology
D017239:Paclitaxel; D002945:Cisplatin