Effect of the chronic combined administration of cisplatin and paclitaxel in a rat model of peripheral neurotoxicity

Eur J Cancer. 2009 Mar;45(4):656-65. doi: 10.1016/j.ejca.2008.10.038. Epub 2008 Dec 16.

Abstract

We have characterised for the first time the general and neurological side effects experienced when using a series of chronic non-lethal cisplatin + paclitaxel schedules in Wistar rats, selected according to our previous experience and the animals' maximum tolerated dose. At the pathological level, the use of combination schedules was definitely more toxic at the kidney and sternal bone marrow level than the single-agent schedules. At the neurophysiological examination based on the assessment of the nerve conduction velocity measurement in the tail nerve, we identified only one combination schedule that was more neurotoxic than the similar schedules based on single-agent administration. This observation was confirmed by the neuropathological examination performed on the sciatic nerve, dorsal root ganglia, ventral and dorsal roots. Our study supports the hypothesis that the general and, to a lesser extent, neurological effects of a combination of cisplatin and paclitaxel are different from those of the administration of both drugs as single agents. We believe that these models may be useful for testing neuroprotective strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / toxicity*
  • Bone Marrow Diseases / chemically induced
  • Bone Marrow Diseases / pathology
  • Cisplatin / administration & dosage
  • Cisplatin / toxicity
  • Disease Models, Animal
  • Drug Administration Schedule
  • Female
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / pathology
  • Neurotoxicity Syndromes / etiology*
  • Neurotoxicity Syndromes / pathology
  • Paclitaxel / administration & dosage
  • Paclitaxel / toxicity
  • Peripheral Nervous System Diseases / chemically induced*
  • Peripheral Nervous System Diseases / pathology
  • Rats
  • Rats, Wistar
  • Weight Loss / drug effects

Substances

  • Paclitaxel
  • Cisplatin