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Persistent chemoneuropathy in patients receiving the plant alkaloids paclitaxel and vincristine

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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.

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References

  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 46:1131–1137

    Article  PubMed  CAS  Google Scholar 

  2. Boyette-Davis J, Dougherty PM (2011) Protection against oxaliplatin-induced mechanical hyperalgesia and intraepidermal nerve fiber loss by minocycline. Exp Neurol 229:353–357

    Article  PubMed  CAS  Google Scholar 

  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 152:308–313

    Article  PubMed  CAS  Google Scholar 

  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 Pain

  5. Burakgazi AZ, Messersmith W, Vaidya D, Hauer P, Hoke A, Polydefkis M (2011) Longitudinal assessment of oxaliplatin-induced neuropathy. Neurology 77:980–986

    Article  PubMed  CAS  Google Scholar 

  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 8:296–306

    Article  PubMed  CAS  Google Scholar 

  7. Cata JP, Weng H-R, Dougherty PM (2006) Clinical and experimental findings in humans and animals with chemotherapy-induced peripheral neuropathy. Minerva Anes 72:151–169

    CAS  Google Scholar 

  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 75:1141–1150

    Article  PubMed  CAS  Google Scholar 

  9. Chaudhry V, Chaudhry M, Crawford TO, Simmons-O’Brien E, Griffin JW (2003) Toxic neuropathy in patients with pre-existing neuropathy. Neurology 60:337–340

    Article  PubMed  CAS  Google Scholar 

  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 33:166–179

    Article  PubMed  CAS  Google Scholar 

  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 109:132–142

    Article  PubMed  CAS  Google Scholar 

  12. Fuchs PN, Campbell JN, Meyer RA (2000) Secondary hyperalgesia persists in capsaicin desensitized skin. Pain 84:141–149

    Article  PubMed  CAS  Google Scholar 

  13. Grunberg SM, Sonka S, Stevenson LL, Muggia FM (1989) Progressive paresthesias after cessation of therapy with very high-dose cisplatin. Cancer Chemother Pharmacol 25:62–64

    Article  PubMed  CAS  Google Scholar 

  14. Kennedy WR, Wendelschafer-Crabb G, Johnson T (1996) Quantitation of epidermal nerves in diabetic neuropathy. Neurology 47:1042–1048

    Article  PubMed  CAS  Google Scholar 

  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 10:202–208

    Article  PubMed  Google Scholar 

  16. Lobert S, Vulevic B, Correia JJ (1996) Interaction of vinca alkaloids with tubulin: a comparison of vinblastine, vincristine and vinorelbine. Biochemistry 35:6806–6814

    Article  PubMed  CAS  Google Scholar 

  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 57:25–32

    Article  PubMed  CAS  Google Scholar 

  18. Oaklander AL (2001) The density of remaining nerve endings in human skin with and without postherpetic neuralgia after shingles. Pain 92:139–145

    Article  PubMed  CAS  Google Scholar 

  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 1168:46–59

    Article  PubMed  CAS  Google Scholar 

  20. Petersen KL, Rice FL, Farhadi M, Reda H, Rowbotham MC (2010) Natural history of cutaneous innervation following herpes zoster. Pain 150:75–82

    Article  PubMed  Google Scholar 

  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 6:5

  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 15:23–27

    Article  CAS  Google Scholar 

  23. Raghavan S, Harvey AD, Humble SR (2011) New opioid side effects and implications for long-term therapy. Trends Anaesth Crit Care 1:18–21

    Article  Google Scholar 

  24. Raymond E, Faivre S, Woynarowski JM, Chaney SG (1998) Oxaliplatin: mechanism of action and antineoplastic activity. Semin Oncol 25:4–12

    PubMed  CAS  Google Scholar 

  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 3:204–214

    Article  Google Scholar 

  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 76:1219–1230

    Article  PubMed  CAS  Google Scholar 

  27. Schiff PB, Horwitz SB (1980) Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci USA 77:1561–1565

    Article  PubMed  CAS  Google Scholar 

  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 201:507–514

    Article  PubMed  CAS  Google Scholar 

  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 386:18–22

    Article  PubMed  CAS  Google Scholar 

Download references

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.

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Authors and Affiliations

  1. Department of Psychology, York College of Pennsylvania, Appell Life Sciences Building, York, PA, 17403, USA

    Jessica A. Boyette-Davis

  2. Department of Anesthesia and Pain Medicine, The University of Texas MD Anderson Cancer Center, 1400 Holcombe, Houston, TX, 77030, USA

    Juan P. Cata, Larry C. Driver, Diane M. Novy, Brian M. Bruel, Deidre L. Mooring & Patrick M. Dougherty

  3. Department of Neurology, University of Minnesota, 515 Delaware SE, Minneapolis, MN, 55455, USA

    Gwen Wendelschafer-Crabb & William R. Kennedy

  4. 1515 Holcombe BLVD, Unit 0409, Houston, TX, 77030, USA

    Patrick M. Dougherty

Authors
  1. Jessica A. Boyette-Davis
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  2. Juan P. Cata
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  7. Gwen Wendelschafer-Crabb
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  8. William R. Kennedy
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  9. Patrick M. Dougherty
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Corresponding author

Correspondence to Patrick M. Dougherty.

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Boyette-Davis, J.A., Cata, J.P., Driver, L.C. et al. Persistent chemoneuropathy in patients receiving the plant alkaloids paclitaxel and vincristine. Cancer Chemother Pharmacol 71, 619–626 (2013). https://doi.org/10.1007/s00280-012-2047-z

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  • DOI: https://doi.org/10.1007/s00280-012-2047-z

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