Advertisement

Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 3, pp 619–626 | Cite as

Persistent chemoneuropathy in patients receiving the plant alkaloids paclitaxel and vincristine

  • Jessica A. Boyette-Davis
  • Juan P. Cata
  • Larry C. Driver
  • Diane M. Novy
  • Brian M. Bruel
  • Deidre L. Mooring
  • Gwen Wendelschafer-Crabb
  • William R. Kennedy
  • Patrick M. DoughertyEmail author
Original Article

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.

Keywords

Chemoneuropathy Paclitaxel Vincristine Epidermal nerve fiber Meissner’s corpuscles 

Notes

Acknowledgments

The work was supported by grants NS046606 and CA124787 and by a gift from the Peggy and Avinash Ahuja Center of Excellence in Pain Research and Treatment. The authors would like to thank Dr. Allen Burton and Dr. Sergio Giralt for their assistance with data collection.

References

  1. 1.
    Argyriou AA, Polychronopoulos P, Iconomou G, Koutras A, Makatsoris T, Gerolymos MK, Gourzis P, Assimakopoulos K, Kalofonos HP, Chroni E (2007) Incidence and characteristics of peripheral neuropathy during oxaliplatin-based chemotherapy for metastatic colon cancer. Acta Oncol 46:1131–1137PubMedCrossRefGoogle Scholar
  2. 2.
    Boyette-Davis J, Dougherty PM (2011) Protection against oxaliplatin-induced mechanical hyperalgesia and intraepidermal nerve fiber loss by minocycline. Exp Neurol 229:353–357PubMedCrossRefGoogle Scholar
  3. 3.
    Boyette-Davis J, Xin W, Zhang H, Dougherty PM (2011) Intraepidermal nerve fiber loss corresponds to the development of Taxol-induced hyperalgesia and can be prevented by treatment with minocycline. Pain 152:308–313PubMedCrossRefGoogle Scholar
  4. 4.
    Boyette-Davis JA, Cata JP, Zhang H, Driver LC, Wendelschafer-Crabb G, Kennedy WR Dougherty PM (2011) Follow-up psychophysical studies in bortezomib-related chemoneuropathy patients. J PainGoogle Scholar
  5. 5.
    Burakgazi AZ, Messersmith W, Vaidya D, Hauer P, Hoke A, Polydefkis M (2011) Longitudinal assessment of oxaliplatin-induced neuropathy. Neurology 77:980–986PubMedCrossRefGoogle Scholar
  6. 6.
    Cata JP, Weng H-R, Burton AW, Villareal H, Giralt S, Dougherty PM (2007) Quantitative sensory findings in patients with bortezomib-induced pain. J Pain 8:296–306PubMedCrossRefGoogle Scholar
  7. 7.
    Cata JP, Weng H-R, Dougherty PM (2006) Clinical and experimental findings in humans and animals with chemotherapy-induced peripheral neuropathy. Minerva Anes 72:151–169Google Scholar
  8. 8.
    Cavaletti G, Bogliun G, Marzorati L, Zincone A, Marzola M, Colombo N, Tredici G (1995) Peripheral neurotoxicity of taxol in patients previously treated with cisplatin. Cancer 75:1141–1150PubMedCrossRefGoogle Scholar
  9. 9.
    Chaudhry V, Chaudhry M, Crawford TO, Simmons-O’Brien E, Griffin JW (2003) Toxic neuropathy in patients with pre-existing neuropathy. Neurology 60:337–340PubMedCrossRefGoogle Scholar
  10. 10.
    Dougherty PM, Cata JP, Burton AW, Vu K, Weng HR (2007) Dysfunction in multiple primary afferent fiber subtypes revealed by quantitative sensory testing in patients with chronic vincristine-induced pain. J Pain Symptom Manage 33:166–179PubMedCrossRefGoogle Scholar
  11. 11.
    Dougherty PM, Cata JP, Cordella JV, Burton A, Weng H-R (2004) Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients. Pain 109:132–142PubMedCrossRefGoogle Scholar
  12. 12.
    Fuchs PN, Campbell JN, Meyer RA (2000) Secondary hyperalgesia persists in capsaicin desensitized skin. Pain 84:141–149PubMedCrossRefGoogle Scholar
  13. 13.
    Grunberg SM, Sonka S, Stevenson LL, Muggia FM (1989) Progressive paresthesias after cessation of therapy with very high-dose cisplatin. Cancer Chemother Pharmacol 25:62–64PubMedCrossRefGoogle Scholar
  14. 14.
    Kennedy WR, Wendelschafer-Crabb G, Johnson T (1996) Quantitation of epidermal nerves in diabetic neuropathy. Neurology 47:1042–1048PubMedCrossRefGoogle Scholar
  15. 15.
    Lauria G, Lombardi R, Borgna M, Penza P, Bianchi R, Savino C, Canta A, Nicolini G, Marmiroli P, Cavaletti G (2005) Intraepidermal nerve fiber density in rat foot pad: neuropathologic-neurophysiologic correlation. J Peripher Nerv Syst 10:202–208PubMedCrossRefGoogle Scholar
  16. 16.
    Lobert S, Vulevic B, Correia JJ (1996) Interaction of vinca alkaloids with tubulin: a comparison of vinblastine, vincristine and vinorelbine. Biochemistry 35:6806–6814PubMedCrossRefGoogle Scholar
  17. 17.
    Miyano K, Tang HB, Nakamura Y, Morioka N, Inoue A, Nakata Y (2009) Paclitaxel and vinorelbine, evoked the release of substance P from cultured rat dorsal root ganglion cells through different PKC isoform-sensitive ion channels. Neuropharmacology 57:25–32PubMedCrossRefGoogle Scholar
  18. 18.
    Oaklander AL (2001) The density of remaining nerve endings in human skin with and without postherpetic neuralgia after shingles. Pain 92:139–145PubMedCrossRefGoogle Scholar
  19. 19.
    Peters CM, Jimenez-Andrade JM, Kuskowski MA, Ghilardi JR, Mantyh PW (2007) An evolving cellular pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous administration of paclitaxel in the rat. Brain Res 1168:46–59PubMedCrossRefGoogle Scholar
  20. 20.
    Petersen KL, Rice FL, Farhadi M, Reda H, Rowbotham MC (2010) Natural history of cutaneous innervation following herpes zoster. Pain 150:75–82PubMedCrossRefGoogle Scholar
  21. 21.
    Pignata S, De PS, Biamonte R, Scambia G, Di VG, Colucci G, Febbraro A, Marinaccio M, Lombardi AV, Manzione L, Carteni G, Nardi M, Danese S, Valerio MR, de MA, Massidda B, Gasparini G, Di MM, Pisano C, Perrone F (2006) Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: the multicenter Italian trial in ovarian cancer (MITO-4) retrospective study. BMC Cancer 6:5Google Scholar
  22. 22.
    Postma TJ, Benard BA, Huijgens PC, Ossenkoppele GJ, Heimans JJ (1993) Long term effects of vincristine on the peripheral nervous system. J Neuro-Onocol 15:23–27CrossRefGoogle Scholar
  23. 23.
    Raghavan S, Harvey AD, Humble SR (2011) New opioid side effects and implications for long-term therapy. Trends Anaesth Crit Care 1:18–21CrossRefGoogle Scholar
  24. 24.
    Raymond E, Faivre S, Woynarowski JM, Chaney SG (1998) Oxaliplatin: mechanism of action and antineoplastic activity. Semin Oncol 25:4–12PubMedGoogle Scholar
  25. 25.
    Rowbotham MC, Yosipovitch G, Connoly MK, Finlay D, Forde G, Fields HL (1996) Cutaneoous innervation density in the allodynic form of postherpetic neuralgia. Neurobiol Dis 3:204–214CrossRefGoogle Scholar
  26. 26.
    Ruff RM, Parker SB (1993) Gender and age-specific changes in motor speed and eye-hand coordination in adults: normative values for finger tapping and grooved pegboard tests. Percept Motor Skills 76:1219–1230PubMedCrossRefGoogle Scholar
  27. 27.
    Schiff PB, Horwitz SB (1980) Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci USA 77:1561–1565PubMedCrossRefGoogle Scholar
  28. 28.
    Siau C, Xiao W, Bennett GJ (2006) Paclitaxel- and vincristine-evoked painful peripheral neuropathies: loss of epidermal innervation and activation of Langerhans cells. Exp Neurol 201:507–514PubMedCrossRefGoogle Scholar
  29. 29.
    Weng HR, Aravindan N, Cata JP, Chen JH, Shaw AD, Dougherty PM (2005) Spinal glial glutamate transporters downregulate in rats with taxol-induced hyperalgesia. Neurosci Lett 386:18–22PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Jessica A. Boyette-Davis
    • 1
  • Juan P. Cata
    • 2
  • Larry C. Driver
    • 2
  • Diane M. Novy
    • 2
  • Brian M. Bruel
    • 2
  • Deidre L. Mooring
    • 2
  • Gwen Wendelschafer-Crabb
    • 3
  • William R. Kennedy
    • 3
  • Patrick M. Dougherty
    • 2
    • 4
    Email author
  1. 1.Department of PsychologyYork College of PennsylvaniaYorkUSA
  2. 2.Department of Anesthesia and Pain MedicineThe University of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Department of NeurologyUniversity of MinnesotaMinneapolisUSA
  4. 4.HoustonUSA

Personalised recommendations