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Subclinical pretreatment sensory deficits appear to predict the development of pain and numbness in patients with multiple myeloma undergoing chemotherapy

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Abstract

Purpose

Chemotherapy-induced peripheral neuropathy is a major complication in the treatment for cancer, including multiple myeloma (MM). Patients may develop painful and non-painful (e.g., numbness) neuropathy symptoms that impair function and often persist after therapy is terminated. This study tested the hypothesis that baseline subclinical neuropathy, as assessed by sensory thresholds, is related to the development of neuropathy symptoms (e.g., pain and numbness) in patients with MM undergoing treatment with chemotherapy.

Methods

Patients (n = 56) who had undergone two or fewer cycles of induction therapy and who had no evident neuropathy were assessed using quantitative sensory tests to determine multiple-modality sensory thresholds. Patient-reported pain and numbness were assessed through induction therapy (16 weeks) via the MD Anderson Symptom Inventory. A subset of participants (n = 15) continued reporting on their symptoms for an additional 16 weeks (“maintenance phase”).

Results

Patients with sharpness detection deficits at baseline (n = 11, 20 % of sample) reported less severe pain and numbness during induction therapy and less numbness during maintenance therapy (P < 0.05). During the maintenance phase, patients with warmth detection deficits (n = 5, 38 % of sample) reported more severe pain and numbness, and those with skin temperature deficits (n = 7, 47 % of maintenance sample) reported more severe pain (P < 0.05). These deficits were related to patient reported difficulty walking, a common symptom of peripheral neuropathy.

Conclusion

Our results suggest that baseline subclinical sensory deficits may be related to a patient’s risk for developing chemotherapy-induced peripheral neuropathy.

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References

  1. Aghajanian C, Soignet S, Dizon DS, Pien CS, Adams J, Elliott PJ, Sabbatini P, Miller V, Hensley ML, Pezzulli S, Canales C, Daud A, Spriggs DR (2002) A phase I trial of the novel proteasome inhibitor PS341 in advanced solid tumor malignancies. Clin Cancer Res 8(8):2505–2511

    PubMed  CAS  Google Scholar 

  2. Jagannath S, Durie BG, Wolf J, Camacho E, Irwin D, Lutzky J, McKinley M, Gabayan E, Mazumder A, Schenkein D, Crowley J (2005) Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol 129(6):776–783. doi:10.1111/j.1365-2141.2005.05540.x

    Article  PubMed  CAS  Google Scholar 

  3. Loprinzi CL, Reeves BN, Dakhil SR, Sloan JA, Wolf SL, Burger KN, Kamal A, Le-Lindqwister NA, Soori GS, Jaslowski AJ, Novotny PJ, Lachance DH (2011) Natural history of paclitaxel-associated acute pain syndrome: prospective cohort study NCCTG N08C1. J Clin Oncol 29(11):1472–1478. doi:10.1200/JCO.2010.33.0308

    Article  PubMed  CAS  Google Scholar 

  4. Tofthagen C (2010) Patient perceptions associated with chemotherapy-induced peripheral neuropathy. Clin J Oncol Nurs 14(3):E22–E28. doi:10.1188/10.CJON.E22-E28

    Article  PubMed  Google Scholar 

  5. Chaudhry V, Cornblath DR, Polydefkis M, Ferguson A, Borrello I (2008) Characteristics of bortezomib- and thalidomide-induced peripheral neuropathy. J Peripher Nerv Syst 13(4):275–282. doi:10.1111/j.1529-8027.2008.00193.x

    Article  PubMed  CAS  Google Scholar 

  6. Prince HM, Adena M, Smith DK, Hertel J (2007) Efficacy of single-agent bortezomib vs. single-agent thalidomide in patients with relapsed or refractory multiple myeloma: a systematic comparison. Eur J Haematol 79(2):93–99. doi:10.1111/j.1600-0609.2007.00886.x

    Article  PubMed  CAS  Google Scholar 

  7. Richardson PG, Briemberg H, Jagannath S, Wen PY, Barlogie B, Berenson J, Singhal S, Siegel DS, Irwin D, Schuster M, Srkalovic G, Alexanian R, Rajkumar SV, Limentani S, Alsina M, Orlowski RZ, Najarian K, Esseltine D, Anderson KC, Amato AA (2006) Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib. J Clin Oncol 24(19):3113–3120. doi:10.1200/JCO.2005.04.7779

    Article  PubMed  CAS  Google Scholar 

  8. 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 12(9):1017–1024. doi:10.1016/j.jpain.2011.04.008

    Article  PubMed  Google Scholar 

  9. Cavaletti G, Gilardini A, Canta A, Rigamonti L, Rodriguez-Menendez V, Ceresa C, Marmiroli P, Bossi M, Oggioni N, D’Incalci M, De Coster R (2007) Bortezomib-induced peripheral neurotoxicity: a neurophysiological and pathological study in the rat. Exp Neurol 204(1):317–325. doi:10.1016/j.expneurol.2006.11.010

    Article  PubMed  CAS  Google Scholar 

  10. Chaudhry V, Cornblath DR, Corse A, Freimer M, Simmons-O’Brien E, Vogelsang G (2002) Thalidomide-induced neuropathy. Neurology 59(12):1872–1875

    Article  PubMed  CAS  Google Scholar 

  11. San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Schots R, Jiang B, Mateos MV, Anderson KC, Esseltine DL, Liu K, Cakana A, van de Velde H, Richardson PG (2008) Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 359(9):906–917. doi:10.1056/NEJMoa0801479

    Article  PubMed  CAS  Google Scholar 

  12. Cavaletti G, Jakubowiak AJ (2010) Peripheral neuropathy during bortezomib treatment of multiple myeloma: a review of recent studies. Leuk Lymphoma 51(7):1178–1187. doi:10.3109/10428194.2010.483303

    Article  PubMed  CAS  Google Scholar 

  13. Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L, Yakoub Agha I, Bourhis JH, Garderet L, Pegourie B, Dumontet C, Renaud M, Voillat L, Berthou C, Marit G, Monconduit M, Caillot D, Grobois B, Avet-Loiseau H, Moreau P, Facon T (2006) Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood 108(10):3289–3294. doi:10.1182/blood-2006-05-022962

    Article  PubMed  CAS  Google Scholar 

  14. Mateos MV, Oriol A, Martinez-Lopez J, Gutierrez N, Teruel AI, de Paz R, Garcia-Larana J, Bengoechea E, Martin A, Mediavilla JD, Palomera L, de Arriba F, Gonzalez Y, Hernandez JM, Sureda A, Bello JL, Bargay J, Penalver FJ, Ribera JM, Martin-Mateos ML, Garcia-Sanz R, Cibeira MT, Ramos ML, Vidriales MB, Paiva B, Montalban MA, Lahuerta JJ, Blade J, Miguel JF (2010) Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol 11(10):934–941. doi:10.1016/S1470-2045(10)70187-X

    Article  PubMed  CAS  Google Scholar 

  15. Palumbo A, Bringhen S, Rossi D, Cavalli M, Larocca A, Ria R, Offidani M, Patriarca F, Nozzoli C, Guglielmelli T, Benevolo G, Callea V, Baldini L, Morabito F, Grasso M, Leonardi G, Rizzo M, Falcone AP, Gottardi D, Montefusco V, Musto P, Petrucci MT, Ciccone G, Boccadoro M (2010) Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol 28(34):5101–5109. doi:10.1200/JCO.2010.29.8216

    Article  PubMed  CAS  Google Scholar 

  16. Favis R, Sun Y, van de Velde H, Broderick E, Levey L, Meyers M, Mulligan G, Harousseau JL, Richardson PG, Ricci DS (2011) Genetic variation associated with bortezomib-induced peripheral neuropathy. Pharmacogenet Genomics 21(3):121–129. doi:10.1097/FPC.0b013e3283436b45

    Article  PubMed  CAS  Google Scholar 

  17. Johnson DC, Ramos C, Szubert AJ, Gregory WM, Child JA, Davies FE, Durie BG, Van Ness BG, Morgan GJ (2008) Genetic variation in ADME genes is associated with thalidomide related peripheral neuropathy in multiple myeloma patients. ASH Annu Meet Abstr 112(11):1675

    Google Scholar 

  18. Badros A, Goloubeva O, Dalal JS, Can I, Thompson J, Rapoport AP, Heyman M, Akpek G, Fenton RG (2007) Neurotoxicity of bortezomib therapy in multiple myeloma: a single-center experience and review of the literature. Cancer 110(5):1042–1049. doi:10.1002/cncr.22921

    Article  PubMed  CAS  Google Scholar 

  19. Mateos MV, Hernandez JM, Hernandez MT, Gutierrez NC, Palomera L, Fuertes M, Diaz-Mediavilla J, Lahuerta JJ, de la Rubia J, Terol MJ, Sureda A, Bargay J, Ribas P, de Arriba F, Alegre A, Oriol A, Carrera D, Garcia-Larana J, Garcia-Sanz R, Blade J, Prosper F, Mateo G, Esseltine DL, van de Velde H, San Miguel JF (2006) Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood 108(7):2165–2172. doi:10.1182/blood-2006-04-019778

    Article  PubMed  CAS  Google Scholar 

  20. Bruna J, Ale A, Velasco R, Jaramillo J, Navarro X, Udina E (2011) Evaluation of pre-existing neuropathy and bortezomib retreatment as risk factors to develop severe neuropathy in a mouse model. J Peripher Nerv Syst 16(3):199–212. doi:10.1111/j.1529-8027.2011.00346.x

    Article  PubMed  CAS  Google Scholar 

  21. Cavaletti G, Bogliun G, Marzorati L, Zincone A, Piatti M, Colombo N, Franchi D, La Presa MT, Lissoni A, Buda A, Fei F, Cundari S, Zanna C (2004) Early predictors of peripheral neurotoxicity in cisplatin and paclitaxel combination chemotherapy. Ann Oncol 15(9):1439–1442. doi:10.1093/annonc/mdh348

    Article  PubMed  CAS  Google Scholar 

  22. Dimopoulos MA, Mateos MV, Richardson PG, Schlag R, Khuageva NK, Shpilberg O, Kropff M, Spicka I, Palumbo A, Wu KL, Esseltine DL, Liu K, Deraedt W, Cakana A, Van De Velde H, San Miguel JF (2011) Risk factors for, and reversibility of, peripheral neuropathy associated with bortezomib-melphalan-prednisone in newly diagnosed patients with multiple myeloma: subanalysis of the phase 3 VISTA study. Eur J Haematol 86(1):23–31. doi:10.1111/j.1600-0609.2010.01533.x

    Article  PubMed  CAS  Google Scholar 

  23. Lanzani F, Mattavelli L, Frigeni B, Rossini F, Cammarota S, Petro D, Jann S, Cavaletti G (2008) Role of a pre-existing neuropathy on the course of bortezomib-induced peripheral neurotoxicity. J Peripher Nerv Syst 13(4):267–274. doi:10.1111/j.1529-8027.2008.00192.x

    Article  PubMed  Google Scholar 

  24. He Z, Boyette-Davis JA, Shah ND, Thomas SK, Vichaya EG, Wang XS, Wendelschafer-Crabb G, Kennedy WR, Simone DA, Cleeland CS, Dougherty PM (In Preparation) Subclinical peripheral neuropathy is a common finding in multiple myeloma patients prior to chemotherapy

  25. Boyette-Davis JA, Eng C, Wang XS, Cleeland CS, Wendelschafer-Crabb G, Kennedy WR, Simone DA, Zhang H, Dougherty PM (2012) Subclinical peripheral neuropathy is a common finding in colorectal cancer patients prior to chemotherapy. Clin Cancer Res 18(11):3180–3187. doi:10.1158/1078-0432.CCR-12-0205

    Article  PubMed  CAS  Google Scholar 

  26. Felix ER, Widerstrom-Noga EG (2009) Reliability and validity of quantitative sensory testing in persons with spinal cord injury and neuropathic pain. J Rehabil Res Dev 46(1):69–83

    Article  PubMed  Google Scholar 

  27. Geber C, Klein T, Azad S, Birklein F, Gierthmuhlen J, Huge V, Lauchart M, Nitzsche D, Stengel M, Valet M, Baron R, Maier C, Tolle T, Treede RD (2011) Test-retest and interobserver reliability of quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain (DFNS): a multi-centre study. Pain 152(3):548–556. doi:10.1016/j.pain.2010.11.013

    Article  PubMed  Google Scholar 

  28. Krumova EK, Geber C, Westermann A, Maier C (2012) Neuropathic pain: is quantitative sensory testing helpful? Curr Diab Rep 12(4):393–402. doi:10.1007/s11892-012-0282-7

    Article  PubMed  Google Scholar 

  29. Cata JP, Weng HR, Burton AW, Villareal H, Giralt S, Dougherty PM (2007) Quantitative sensory findings in patients with bortezomib-induced pain. J Pain 8(4):296–306. doi:10.1016/j.jpain.2006.09.014

    Article  PubMed  CAS  Google Scholar 

  30. 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 Manag 33(2):166–179. doi:10.1016/j.jpainsymman.2006.08.006

    Article  CAS  Google Scholar 

  31. Dougherty PM, Cata JP, Cordella JV, Burton A, Weng HR (2004) Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients. Pain 109(1–2):132–142. doi:10.1016/j.pain.2004.01.021

    Article  PubMed  CAS  Google Scholar 

  32. Fuchs PN, Campbell JN, Meyer RA (2000) Secondary hyperalgesia persists in capsaicin desensitized skin. Pain 84(2–3):141–149

    Article  PubMed  CAS  Google Scholar 

  33. Ruff RM, Parker SB (1993) Gender- and age-specific changes in motor speed and eye-hand coordination in adults: normative values for the finger tapping and grooved pegboard tests. Percept Mot Skills 76(3 Pt 2):1219–1230

    Article  PubMed  CAS  Google Scholar 

  34. Cleeland CS, Mendoza TR, Wang XS, Chou C, Harle MT, Morrissey M, Engstrom MC (2000) Assessing symptom distress in cancer patients: the M.D. Anderson Symptom Inventory. Cancer 89(7):1634–1646. doi:10.1002/1097-0142(20001001)89:7<1634:AID-CNCR29>3.0.CO;2-V

    Article  PubMed  CAS  Google Scholar 

  35. Jones D, Vichaya EG, Wang XS, Williams LA, Shah ND, Thomas SK, Johnson VE, Champlin RE, Cleeland CS, Mendoza TR (2013) Validation of the M. D. Anderson symptom inventory multiple myeloma module. J Hematol Oncol 6(1):13. doi:10.1186/1756-8722-6-13

    Article  PubMed  Google Scholar 

  36. Palos GR, Mendoza TR, Mobley GM, Cantor SB, Cleeland CS (2006) Asking the community about cutpoints used to describe mild, moderate, and severe pain. J Pain 7(1):49–56. doi:10.1016/j.jpain.2005.07.012

    Article  PubMed  Google Scholar 

  37. Dispenzieri A, Kyle RA (2005) Neurological aspects of multiple myeloma and related disorders. Best Pract Res Clin Haematol 18(4):673–688. doi:10.1016/j.beha.2005.01.024

    Article  PubMed  CAS  Google Scholar 

  38. Drappatz J, Batchelor T (2004) Neurologic complications of plasma cell disorders. Clin Lymphoma 5(3):163–171

    Article  PubMed  Google Scholar 

  39. Treede RD, Meyer RA, Raja SN, Campbell JN (1995) Evidence for two different heat transduction mechanisms in nociceptive primary afferents innervating monkey skin. J Physiol 483(Pt 3):747–758

    PubMed  CAS  Google Scholar 

  40. Cain DM, Khasabov SG, Simone DA (2001) Response properties of mechanoreceptors and nociceptors in mouse glabrous skin: an in vivo study. J Neurophysiol 85(4):1561–1574

    PubMed  CAS  Google Scholar 

  41. Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, Gentili S, Patriarca F, Nozzoli C, Levi A, Guglielmelli T, Benevolo G, Callea V, Rizzo V, Cangialosi C, Musto P, De Rosa L, Liberati AM, Grasso M, Falcone AP, Evangelista A, Cavo M, Gaidano G, Boccadoro M, Palumbo A (2010) Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood 116(23):4745–4753. doi:10.1182/blood-2010-07-294983

    Article  PubMed  CAS  Google Scholar 

  42. Jagannath S, Barlogie B, Berenson J, Siegel D, Irwin D, Richardson PG, Niesvizky R, Alexanian R, Limentani SA, Alsina M, Adams J, Kauffman M, Esseltine DL, Schenkein DP, Anderson KC (2004) A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol 127(2):165–172. doi:10.1111/j.1365-2141.2004.05188.x

    Article  PubMed  CAS  Google Scholar 

  43. Offidani M, Corvatta L, Marconi M, Malerba L, Mele A, Olivieri A, Brunori M, Catarini M, Candela M, Capelli D, Montanari M, Rupoli S, Leoni P (2004) Common and rare side-effects of low-dose thalidomide in multiple myeloma: focus on the dose-minimizing peripheral neuropathy. Eur J Haematol 72(6):403–409. doi:10.1111/j.1600-0609.2004.00238.x

    Article  PubMed  CAS  Google Scholar 

  44. Rajkumar SV, Hayman SR, Lacy MQ, Dispenzieri A, Geyer SM, Kabat B, Zeldenrust SR, Kumar S, Greipp PR, Fonseca R, Lust JA, Russell SJ, Kyle RA, Witzig TE, Gertz MA (2005) Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 106(13):4050–4053. doi:10.1182/blood-2005-07-2817

    Article  PubMed  CAS  Google Scholar 

  45. Moreau P, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, Grishunina M, Rekhtman G, Masliak Z, Robak T, Shubina A, Arnulf B, Kropff M, Cavet J, Esseltine D-L, Feng H, Girgis S, van de Velde H, Deraedt W, Harousseau J-L (2011) Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol 12(5):431–440

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors wish to acknowledge Jackie Joy and Venus Ilagan for symptom and clinical data collection, Tina Peters and Tony Perez for QST data collection, Gary Mobley and Katherine Gilmore for data management, and Jeanie F. Woodruff, ELS for editorial assistance. This work was supported by the National Cancer Institute at the US National Institutes of Health (CA124787 and NS046606). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

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Authors and Affiliations

  1. Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Elisabeth G. Vichaya, Xin Shelley Wang, Tito R. Mendoza, Loretta A. Williams & Charles S. Cleeland

  2. Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Sheeba K. Thomas

  3. Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Nina Shah

  4. Department of Anesthesia and Pain Medicine, The University of Texas MD Anderson Cancer Center, 1400 Holcombe Blvd., Unit 409, Houston, TX, 77030, USA

    Zijing He & Patrick M. Dougherty

  5. Department of Psychology, York College, York, PA, USA

    Jessica A. Boyette-Davis

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  1. Elisabeth G. Vichaya
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  2. Xin Shelley Wang
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  3. Jessica A. Boyette-Davis
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  7. Nina Shah
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  9. Charles S. Cleeland
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  10. Patrick M. Dougherty
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Correspondence to Patrick M. Dougherty.

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Vichaya, E.G., Wang, X.S., Boyette-Davis, J.A. et al. Subclinical pretreatment sensory deficits appear to predict the development of pain and numbness in patients with multiple myeloma undergoing chemotherapy. Cancer Chemother Pharmacol 71, 1531–1540 (2013). https://doi.org/10.1007/s00280-013-2152-7

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