다발성 골수종 환자에서 Bortezomib에 의한 말초신경병증 발생과 위험인자 분석
Analysis of Incidence and Risk Factors for Bortezomib-induced Peripheral Neuropathy in Multiple Myeloma
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초록
Bortezomib acts by disrupting ubiquitin-proteasome pathway which regulates proteinhomeostasis within the cell and has demonstrated significant activity mainly against recurrent ornewly diagnosed multiple myeloma(MM). Among bortezomib-related side effects, peripheral neuropathy(PN) as main dose-limiting non-haematological toxicity can substantially affect thequality of life of patients. It typically requires dose-reduction, delay, or even premature terminationof successful treatment. Therefore, predicting the risk for neuropathy before the therapyand a proper management of neurotoxicity are very important considerations. The aim of this study was to evaluate the incidence of PN, risk factors, and prior exposure topotentially neurotoxic chemotherapy. A total of 108 patients with multiple myeloma(MM) wereincluded, who received bortezomib in Seoul National University of Hospital(SNUH) from May 2005 to April 2008. A retrospective chart review was performed on SNUH patients’ElectronicMedical Records(EMR), and the SPSS Statistics 19.0 was used for analysis. In univariate analysis, no correlation was found between the development of PN, sex, or age,but creatinine level (Scr≥2)(48% vs 78%, p=0.007, OR=0.264), presence of DM(50% vs 76%,p=0.034, OR=0.324) and number of therapy cycles(N>3)(84% vs 57%, p=0.002, OR=4.046) weresignificantly correlated with PN incidence. In a multivariate logistic regression, the risk of bortezomib-related PN was lower in patients whose creatinine level was high(Scr≥2)(OR=0.248) andgreater in patients treated with high number of bortezomib cylces(N>3)(OR=4.235). Concerning that the prior exposure to chemotherapy could exacerbate neurotoxicity, there waslower incidence of PN in the prior bortezomib treated group(38% vs 62%, p=0.007), prior bortezomibwith thalidomide treated group(36% vs 63%, p=0.003), and prior bortezomib with vincristinetreated group(37% vs 60%, p=0.026).
Abstract
Bortezomib acts by disrupting ubiquitin-proteasome pathway which regulates proteinhomeostasis within the cell and has demonstrated significant activity mainly against recurrent ornewly diagnosed multiple myeloma(MM). Among bortezomib-related side effects, peripheral neuropathy(PN) as main dose-limiting non-haematological toxicity can substantially affect thequality of life of patients. It typically requires dose-reduction, delay, or even premature terminationof successful treatment. Therefore, predicting the risk for neuropathy before the therapyand a proper management of neurotoxicity are very important considerations. The aim of this study was to evaluate the incidence of PN, risk factors, and prior exposure topotentially neurotoxic chemotherapy. A total of 108 patients with multiple myeloma(MM) wereincluded, who received bortezomib in Seoul National University of Hospital(SNUH) from May 2005 to April 2008. A retrospective chart review was performed on SNUH patients’ElectronicMedical Records(EMR), and the SPSS Statistics 19.0 was used for analysis. In univariate analysis, no correlation was found between the development of PN, sex, or age,but creatinine level (Scr≥2)(48% vs 78%, p=0.007, OR=0.264), presence of DM(50% vs 76%,p=0.034, OR=0.324) and number of therapy cycles(N>3)(84% vs 57%, p=0.002, OR=4.046) weresignificantly correlated with PN incidence. In a multivariate logistic regression, the risk of bortezomib-related PN was lower in patients whose creatinine level was high(Scr≥2)(OR=0.248) andgreater in patients treated with high number of bortezomib cylces(N>3)(OR=4.235). Concerning that the prior exposure to chemotherapy could exacerbate neurotoxicity, there waslower incidence of PN in the prior bortezomib treated group(38% vs 62%, p=0.007), prior bortezomibwith thalidomide treated group(36% vs 63%, p=0.003), and prior bortezomib with vincristinetreated group(37% vs 60%, p=0.026).
참고문헌 (27)
- "Uptodate.com-Clinical features, laboratory manifestations, and diagnosis of multiple myeloma", ~
- Delforge M, "Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues", The Lancet Oncology, 11(11), pp.1086~1095 (2010)
- Mateos M.V., "Management of treatmentrelated adverse events in patients with multiple myeloma", Cancer Treatment Reviews, (Suppl 2), pp.24~32 (2010)
- Badros A., "Neurotoxicity of bortezomib therapy in multiple myeloma: a single-center experience and review of the literature", Cancer, 110(5), pp.1042~1049 (2007)
- "Micromedex.com-drug information of borte zomib", ~
- Richardson P. G., "Single-agent bortezomib in previously untreated multiple myeloma:efficacy, characterization of peripheral neuropathy, and molecular correlations with response and neuropathy", Journal of Clinical Oncology, 27(21), pp.3518~3525 (2009)
- Richardson P. G., "Bortezomib or high-dose dexamethasone for relapsed multiple myeloma", N Engl J Med, 352, pp.2487~2498 (2005)
- Richardson P. G., "Safety and efficacy of bortezomib in high-risk and elderly patients with relapsed multiple myeloma", Br J Haematol, 137, pp.429~435 (2007)
- San Miguel J. F., "Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma", N Engl J Med, 359, pp.906~917 (2008)
- Argyriou A.A, "Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature", Blood, 112(5), pp.1593~1599 (2008)
- Mateos M.V, "A prospective, multicenter, randomized, trial of bortezomib", melphalan, thalidomide, pp.prednisone(VTP) as induction therapy followed by maintenance treatment with bortezomib, thalidomide(VT) versus bortezomib[DOI]
- Bang S.M., "A multicenter retrospective analysis of adverse events in Korean patients using bortezomib for multiple myeloma", International Journal of Hematology, 83(4), pp.309~313 (2006)
- Corso A, "Bortezomib-induced peripheral neuropathy in multiple myeloma: a comparison between previously treated and untreated patients", Leukemia Research, 34(4), pp.471~474 (2010)
- Argyriou A.A., "Chemotherapy-induced peripheral neurotoxicity(CIPN): An update", Critical Reviews in Oncology, 2012, pp.82, 50~77
- Cata J.P., "Quantitative sensory findings in patients with bortezomib-induced pain", J Pain, 8, pp.296~306 (2007)
- Calhoun E.A, "Psychometric evaluation of the functional assessment of cancer therapy", gynecologic oncology group-neurotoxicity (Fact, Int J Gynecol Cancer, pp.2003, 13[DOI]
- Richardson P. G., "Frequency characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib", J Clin Oncol, 24, pp.3013~3020 (2006)
- Gilardini A., "Proteasome inhibition: a promising strategy for treating cancer, but what about neurotoxicity?", Curr Med Chem, 15, pp.3025~3035 (2008)
- Mohty B., "Peripheral neuropathy and new treatments for multiple myeloma: background and practical recommendations", Haematologica, 95, pp.311~319 (2010)
- Yanssenkorea, "Velcade(bortezomib) IV insert paper", ~
- Mateos M. V., "Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1", 2study, 2006, pp.108(7), 2165~2172
- Richardson P. G., "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(6), pp.895~903 (2009)
- El-Cheikh J., "Features and risk factors of peripheral neuropathy during treatment with bortezomib for advanced multiple myeloma", Clin Lymphoma Myeloma, 8(3), pp.146~152 (2008)
- Silberman J., "Review of peripheral neuropathy in plasma cell disorders", Hematol Oncol, 26(2), pp.55~65 (2008)
- Borrello I., "Bortezomib and Thalidomide Treatment of Newly Diagnosed Patients with Multiple Myeloma - Efficacy and Neurotoxicity", ASH Annual Meeting Blood, 108(11), pp.3579~ (2006)
- Richardson P.G., "A Multicenter Phase II Trial of Bortezomib in Patients with Previously Untreated Multiple Myeloma:Efficacy with Manageable Toxicity in Patients with Unexpectedly High Rates of Baseline Peripheral Neuropathy", Blood ASH Annual Meeting, 106(11), pp.2548~ (2005)
- Favis R., "Genetic variation associated with bortezomib-induced peripheral neuropathy", Pharmacogenet Genomics, 21(3), pp.121~129 (2011)