Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Supportive Care in Cancer
Published in: Supportive Care in Cancer 10/2014

01-10-2014 | Original Article

Impact of dose modification on intravenous Bortezomib-induced peripheral neuropathy in multiple myeloma patients

Authors: Juhee Cho, Danbee Kang, Ji Yean Lee, Kihyun Kim, Seok Jin Kim

Published in: Supportive Care in Cancer | Issue 10/2014

Login to get access

Abstract

Purpose

Patients discontinue bortezomib treatment despite good response to the therapy because of bortezomib-induced neuropathy. Early and active dose reduction is recommended for efficacy of treatment. This study evaluates patterns of bortezomib-associated neuropathy and examines the effectiveness of dose modification on symptom management and treatment compliance.

Methods

This is a retrospective cohort study of multiple myeloma patients who received bortezomib intravenously from 2009 to 2012 at Samsung Medical Center, Seoul, Korea. Peripheral neuropathy was assessed using neurotoxicity subscale of the FACT/GOG-Ntx at daily clinical practice; physicians modified the dosage and schedule of bortezomib treatment. Mixed-effect models were used for evaluating changes of neuropathy symptoms over time. Linear spline models and multivariate logistic regression were used for testing the effectiveness of interventions.

Results

There were 1,060 visits of 55 multiple myeloma patients during the study period. Patients were most likely to have numbness of feet, painful burning in feet, muscle weakness, and the symptoms worsened over time (P < 0.05). For patients who received intervention (n = 32, 58.1 %), neuropathy symptoms were significantly decreased after the intervention (coefficient, −0.1 (95 % confidence interval (CI), −0.8, 0.6)). The intervention group had on average 5.19 (95 % CI, 3.79, 6.59) more bortezomib administrations and was 1.4 times more likely to complete the treatment (odds ratio, 1.40 (95 % CI, 0.31, 6.32)) than the nonintervention group.

Conclusion

Close monitoring of peripheral neuropathy in patients receiving bortezomib is a feasible and useful way to manage neuropathy in the real world.
Literature
1.
Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, Rajkumar SV, Srkalovic G, Alsina M, Alexanian R, Siegel D, Orlowski RZ, Kuter D, Limentani SA, Lee S, Hideshima T, Esseltine DL, Kauffman M, Adams J, Schenkein DP, Anderson KC (2003) A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 348:2609–2617PubMedCrossRef
2.
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, Investigators VT (2008) Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 359:906–917PubMedCrossRef
3.
Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, San-Miguel JF, Blade J, Boccadoro M, Cavenagh J, Dalton WS, Boral AL, Esseltine DL, Porter JB, Schenkein D, Anderson KC (2005) Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 352:2487–2498PubMedCrossRef
4.
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 24:3113–3120PubMedCrossRef
5.
Min CK, Lee MJ, Eom KS, Lee S, Lee JW, Min WS, Kim CC, Kim M, Lim J, Kim Y, Han K (2007) Bortezomib in combination with conventional chemotherapeutic agents for multiple myeloma compared with bortezomib alone. Jpn J Clin Oncol 37:961–968PubMedCrossRef
6.
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 204:317–325PubMedCrossRef
7.
Meregalli C, Chiorazzi A, Carozzi VA, Canta A, Sala B, Colombo M, Oggioni N, Ceresa C, Foudah D, La Russa F, Miloso M, Nicolini G, Marmiroli P, Bennett DL, Cavaletti G (2014) Evaluation of tubulin polymerization and chronic inhibition of proteasome as citotoxicity mechanisms in bortezomib-induced peripheral neuropathy. Cell Cycle 13:612–621PubMedCrossRef
8.
Azoulay D, Lavie D, Horowitz N, Suriu C, Gatt ME, Akria L, Perlman R, Braester A, Ben-Yehuda D (2014) Bortezomib-induced peripheral neuropathy is related to altered levels of brain-derived neurotrophic factor in the peripheral blood of patients with multiple myeloma. Br J Haematol 164:454–456PubMedCrossRef
9.
Becker PS (2011) Genetic predisposition for chemotherapy-induced neuropathy in multiple myeloma. J Clin Oncol 29:783–786PubMedCrossRef
10.
Broyl A, Corthals SL, Jongen JL, van der Holt B, Kuiper R, de Knegt Y, van Duin M, el Jarari L, Bertsch U, Lokhorst HM, Durie BG, Goldschmidt H, Sonneveld P (2010) Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: a prospective analysis of data from the HOVON-65/GMMG-HD4 trial. Lancet Oncol 11:1057–1065PubMedCrossRef
11.
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 110:1042–1049PubMedCrossRef
12.
Richardson PG, Sonneveld P, Schuster MW, Stadtmauer EA, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, Blade J, Boccadoro M, Cavenagh JD, Boral AL, Esseltine DL, Wen PY, Amato AA, Anderson KC, San Miguel J (2009) Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX trial in relapsed multiple myeloma: impact of a dose-modification guideline. Br J Haematol 144:895–903PubMedCrossRef
13.
Dworkin RH, O'Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, Kalso EA, Loeser JD, Miaskowski C, Nurmikko TJ, Portenoy RK, Rice AS, Stacey BR, Treede RD, Turk DC, Wallace MS (2007) Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 132:237–251PubMedCrossRef
14.
Sonneveld P, Jongen JL (2010) Dealing with neuropathy in plasma-cell dyscrasias. Hematology Am Soc Hematol Educ Program 2010:423–430PubMedCrossRef
15.
16.
Calhoun EA, Welshman EE, Chang CH, Lurain JR, Fishman DA, Hunt TL, Cella D (2003) Psychometric evaluation of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire for patients receiving systemic chemotherapy. Int J Gynecol Cancer 13:741–748PubMedCrossRef
17.
Talamo G, Farooq U, Zangari M, Liao J, Dolloff NG, Loughran TP Jr, Epner E (2010) Beyond the CRAB symptoms: a study of presenting clinical manifestations of multiple myeloma. Clin Lymphoma Myeloma Leuk 10:464–468PubMedCrossRef
18.
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 86:23–31PubMedCrossRef
19.
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 13:267–274PubMedCrossRef
20.
Chaudhry V, Cornblath DR, Polydefkis M, Ferguson A, Borrello I (2008) Characteristics of bortezomib- and thalidomide-induced peripheral neuropathy. J Peripher Nerv Syst 13:275–282PubMedCentralPubMedCrossRef
21.
Corso A, Mangiacavalli S, Varettoni M, Pascutto C, Zappasodi P, Lazzarino M (2010) Bortezomib-induced peripheral neuropathy in multiple myeloma: a comparison between previously treated and untreated patients. Leuk Res 34:471–474PubMedCrossRef
22.
Richardson PG, Delforge M, Beksac M, Wen P, Jongen JL, Sezer O, Terpos E, Munshi N, Palumbo A, Rajkumar SV, Harousseau JL, Moreau P, Avet-Loiseau H, Lee JH, Cavo M, Merlini G, Voorhees P, Chng WJ, Mazumder A, Usmani S, Einsele H, Comenzo R, Orlowski R, Vesole D, Lahuerta JJ, Niesvizky R, Siegel D, Mateos MV, Dimopoulos M, Lonial S, Jagannath S, Blade J, Miguel JS, Morgan G, Anderson KC, Durie BG, Sonneveld P (2012) Management of treatment-emergent peripheral neuropathy in multiple myeloma. Leukemia 26:595–608PubMedCrossRef
23.
Arnulf B, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, van de Velde H, Feng H, Cakana A, Deraedt W, Moreau P (2012) Updated survival analysis of a randomized phase III study of subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma. Haematologica 97:1925–1928PubMedCentralPubMedCrossRef
24.
Mateos MV, San Miguel JF (2012) Safety and efficacy of subcutaneous formulation of bortezomib versus the conventional intravenous formulation in multiple myeloma. Ther Adv Hematol 3:117–124PubMedCentralPubMedCrossRef
Metadata
Title
Impact of dose modification on intravenous Bortezomib-induced peripheral neuropathy in multiple myeloma patients
Authors
Juhee Cho
Danbee Kang
Ji Yean Lee
Kihyun Kim
Seok Jin Kim
Publication date
01-10-2014
Publisher
Springer Berlin Heidelberg
Published in
Supportive Care in Cancer / Issue 10/2014
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-014-2256-6

Other articles of this Issue 10/2014

Supportive Care in Cancer 10/2014 Go to the issue

Original Article

Magnitude of score change for the palliative prognostic index for survival prediction in patients with poor prognostic terminal cancer

Erratum

Erratum to: Characteristics and outcomes of advanced cancer patients who miss outpatient supportive care consult appointments

Original Article

Quality of life and satisfaction with care among family caregivers of patients with recurrent or metastasized digestive cancer requiring palliative care

Original Article

Active treatment given in the last weeks of life: poor quality cancer care or justifiable behavior?

Original Article

A qualitative study investigating chemotherapy-induced nausea as a symptom cluster

Original Article

Characteristics and outcomes of advanced cancer patients who miss outpatient supportive care consult appointments
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits