Skip to main content
Erschienen in: Cancer Chemotherapy and Pharmacology 3/2013

01.03.2013 | Original Article

Persistent chemoneuropathy in patients receiving the plant alkaloids paclitaxel and vincristine

verfasst von: 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. Dougherty

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 3/2013

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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 46:1131–1137PubMedCrossRef 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 46:1131–1137PubMedCrossRef
2.
Zurück zum Zitat Boyette-Davis J, Dougherty PM (2011) Protection against oxaliplatin-induced mechanical hyperalgesia and intraepidermal nerve fiber loss by minocycline. Exp Neurol 229:353–357PubMedCrossRef Boyette-Davis J, Dougherty PM (2011) Protection against oxaliplatin-induced mechanical hyperalgesia and intraepidermal nerve fiber loss by minocycline. Exp Neurol 229:353–357PubMedCrossRef
3.
Zurück zum Zitat 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 152:308–313PubMedCrossRef 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 152:308–313PubMedCrossRef
4.
Zurück zum Zitat 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 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.
Zurück zum Zitat Burakgazi AZ, Messersmith W, Vaidya D, Hauer P, Hoke A, Polydefkis M (2011) Longitudinal assessment of oxaliplatin-induced neuropathy. Neurology 77:980–986PubMedCrossRef Burakgazi AZ, Messersmith W, Vaidya D, Hauer P, Hoke A, Polydefkis M (2011) Longitudinal assessment of oxaliplatin-induced neuropathy. Neurology 77:980–986PubMedCrossRef
6.
Zurück zum Zitat 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 8:296–306PubMedCrossRef 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 8:296–306PubMedCrossRef
7.
Zurück zum Zitat 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 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
8.
Zurück zum Zitat 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 75:1141–1150PubMedCrossRef 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 75:1141–1150PubMedCrossRef
9.
Zurück zum Zitat Chaudhry V, Chaudhry M, Crawford TO, Simmons-O’Brien E, Griffin JW (2003) Toxic neuropathy in patients with pre-existing neuropathy. Neurology 60:337–340PubMedCrossRef Chaudhry V, Chaudhry M, Crawford TO, Simmons-O’Brien E, Griffin JW (2003) Toxic neuropathy in patients with pre-existing neuropathy. Neurology 60:337–340PubMedCrossRef
10.
Zurück zum Zitat 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 33:166–179PubMedCrossRef 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 33:166–179PubMedCrossRef
11.
Zurück zum Zitat 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 109:132–142PubMedCrossRef 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 109:132–142PubMedCrossRef
12.
Zurück zum Zitat Fuchs PN, Campbell JN, Meyer RA (2000) Secondary hyperalgesia persists in capsaicin desensitized skin. Pain 84:141–149PubMedCrossRef Fuchs PN, Campbell JN, Meyer RA (2000) Secondary hyperalgesia persists in capsaicin desensitized skin. Pain 84:141–149PubMedCrossRef
13.
Zurück zum Zitat Grunberg SM, Sonka S, Stevenson LL, Muggia FM (1989) Progressive paresthesias after cessation of therapy with very high-dose cisplatin. Cancer Chemother Pharmacol 25:62–64PubMedCrossRef Grunberg SM, Sonka S, Stevenson LL, Muggia FM (1989) Progressive paresthesias after cessation of therapy with very high-dose cisplatin. Cancer Chemother Pharmacol 25:62–64PubMedCrossRef
14.
Zurück zum Zitat Kennedy WR, Wendelschafer-Crabb G, Johnson T (1996) Quantitation of epidermal nerves in diabetic neuropathy. Neurology 47:1042–1048PubMedCrossRef Kennedy WR, Wendelschafer-Crabb G, Johnson T (1996) Quantitation of epidermal nerves in diabetic neuropathy. Neurology 47:1042–1048PubMedCrossRef
15.
Zurück zum Zitat 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 10:202–208PubMedCrossRef 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 10:202–208PubMedCrossRef
16.
Zurück zum Zitat Lobert S, Vulevic B, Correia JJ (1996) Interaction of vinca alkaloids with tubulin: a comparison of vinblastine, vincristine and vinorelbine. Biochemistry 35:6806–6814PubMedCrossRef Lobert S, Vulevic B, Correia JJ (1996) Interaction of vinca alkaloids with tubulin: a comparison of vinblastine, vincristine and vinorelbine. Biochemistry 35:6806–6814PubMedCrossRef
17.
Zurück zum Zitat 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 57:25–32PubMedCrossRef 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 57:25–32PubMedCrossRef
18.
Zurück zum Zitat Oaklander AL (2001) The density of remaining nerve endings in human skin with and without postherpetic neuralgia after shingles. Pain 92:139–145PubMedCrossRef Oaklander AL (2001) The density of remaining nerve endings in human skin with and without postherpetic neuralgia after shingles. Pain 92:139–145PubMedCrossRef
19.
Zurück zum Zitat 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 1168:46–59PubMedCrossRef 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 1168:46–59PubMedCrossRef
20.
Zurück zum Zitat Petersen KL, Rice FL, Farhadi M, Reda H, Rowbotham MC (2010) Natural history of cutaneous innervation following herpes zoster. Pain 150:75–82PubMedCrossRef Petersen KL, Rice FL, Farhadi M, Reda H, Rowbotham MC (2010) Natural history of cutaneous innervation following herpes zoster. Pain 150:75–82PubMedCrossRef
21.
Zurück zum Zitat 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 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.
Zurück zum Zitat Postma TJ, Benard BA, Huijgens PC, Ossenkoppele GJ, Heimans JJ (1993) Long term effects of vincristine on the peripheral nervous system. J Neuro-Onocol 15:23–27CrossRef Postma TJ, Benard BA, Huijgens PC, Ossenkoppele GJ, Heimans JJ (1993) Long term effects of vincristine on the peripheral nervous system. J Neuro-Onocol 15:23–27CrossRef
23.
Zurück zum Zitat Raghavan S, Harvey AD, Humble SR (2011) New opioid side effects and implications for long-term therapy. Trends Anaesth Crit Care 1:18–21CrossRef Raghavan S, Harvey AD, Humble SR (2011) New opioid side effects and implications for long-term therapy. Trends Anaesth Crit Care 1:18–21CrossRef
24.
Zurück zum Zitat Raymond E, Faivre S, Woynarowski JM, Chaney SG (1998) Oxaliplatin: mechanism of action and antineoplastic activity. Semin Oncol 25:4–12PubMed Raymond E, Faivre S, Woynarowski JM, Chaney SG (1998) Oxaliplatin: mechanism of action and antineoplastic activity. Semin Oncol 25:4–12PubMed
25.
Zurück zum Zitat 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 3:204–214CrossRef 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 3:204–214CrossRef
26.
Zurück zum Zitat 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 76:1219–1230PubMedCrossRef 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 76:1219–1230PubMedCrossRef
27.
Zurück zum Zitat Schiff PB, Horwitz SB (1980) Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci USA 77:1561–1565PubMedCrossRef Schiff PB, Horwitz SB (1980) Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci USA 77:1561–1565PubMedCrossRef
28.
Zurück zum Zitat 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 201:507–514PubMedCrossRef 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 201:507–514PubMedCrossRef
29.
Zurück zum Zitat 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 386:18–22PubMedCrossRef 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 386:18–22PubMedCrossRef
Metadaten
Titel
Persistent chemoneuropathy in patients receiving the plant alkaloids paclitaxel and vincristine
verfasst von
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. Dougherty
Publikationsdatum
01.03.2013
Verlag
Springer-Verlag
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 3/2013
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-012-2047-z

Weitere Artikel der Ausgabe 3/2013

Cancer Chemotherapy and Pharmacology 3/2013 Zur Ausgabe

Bessere Prognose mit links- statt rechtsseitigem Kolon-Ca.

06.05.2024 Kolonkarzinom Nachrichten

Menschen mit linksseitigem Kolonkarzinom leben im Mittel zweieinhalb Jahre länger als solche mit rechtsseitigem Tumor. Auch aktuell ist das Sterberisiko bei linksseitigen Tumoren US-Daten zufolge etwa um 11% geringer als bei rechtsseitigen.

Nodal-negativ nach neoadjuvanter Chemo: Axilladissektion verzichtbar?

03.05.2024 Mammakarzinom Nachrichten

Wenn bei Mammakarzinomen durch eine neoadjuvante Chemotherapie ein Downstaging von nodal-positiv zu nodal-negativ gelingt, scheint es auch ohne Axilladissektion nur selten zu axillären Rezidiven zu kommen.

Wo hapert es noch bei der Umsetzung der POMGAT-Leitlinie?

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Bestrahlung nach Prostatektomie: mehr Schaden als Nutzen?

02.05.2024 Prostatakarzinom Nachrichten

Eine adjuvante Radiotherapie nach radikaler Prostata-Op. bringt den Betroffenen wahrscheinlich keinen Vorteil. Im Gegenteil: Durch die Bestrahlung steigt offenbar das Risiko für Harn- und Stuhlinkontinenz.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.