Persistent chemoneuropathy in patients receiving the plant alkaloids paclitaxel and vincristine

Cancer Chemother Pharmacol. 2013 Mar;71(3):619-26. doi: 10.1007/s00280-012-2047-z. Epub 2012 Dec 11.

Abstract

Purpose: Chemoneuropathy remains a painful, burdensome complication of cancer treatment for patients receiving a range of chemotherapeutics, yet the cause and persistence of this condition are not fully documented. This study was designed to quantify the longevity of and contributions to neuropathy following treatment with the plant alkaloids paclitaxel and vincristine.

Methods: Quantitative sensory testing was conducted approximately 18 months apart on 14 patients, seven of which had been treated with paclitaxel and seven with vincristine and compared to data from 18 healthy control subjects. In addition, skin biopsies were obtained to investigate changes in the density of Meissner's corpuscles and epidermal nerve fibers (ENFs), the loss of which is thought to contribute to multiple forms of neuropathy.

Results: Impairments in motor skills, as measured by a grooved peg-board, were found. Deficits in touch detection were observed using von Frey monofilaments, as were changes in sharpness detection using a weighted needle device. Using a Peltier device, warmth and heat detection were impaired. These deficits were consistent across time. Remarkably, the average length of time patients reported painful neuropathy was over four and a half years. Skin biopsies were found to be deficient in Meissner's corpuscles and ENFs.

Conclusions: The combination of widespread deficits in sensory testing and decreases in skin innervation for cancer patients receiving paclitaxel or vincristine document a persistent polyneuropathy which severely impacts these patients. Decreases in Meissner's corpuscles and ENFs indicate a possible mechanism for the neuropathy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents, Phytogenic / adverse effects*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Biopsy
  • Female
  • Humans
  • Male
  • Mechanoreceptors / drug effects
  • Middle Aged
  • Motor Skills / drug effects
  • Nerve Fibers / pathology
  • Neurotoxicity Syndromes / pathology*
  • Paclitaxel / adverse effects*
  • Paclitaxel / therapeutic use
  • Pain / chemically induced
  • Pain Measurement / drug effects
  • Peripheral Nervous System Diseases / chemically induced*
  • Peripheral Nervous System Diseases / pathology
  • Physical Stimulation
  • Pilot Projects
  • Sensory Thresholds / drug effects
  • Skin / innervation
  • Skin / pathology
  • Thermosensing / drug effects
  • Touch / drug effects
  • Vincristine / adverse effects*
  • Vincristine / therapeutic use

Substances

  • Antineoplastic Agents, Phytogenic
  • Vincristine
  • Paclitaxel