Abstract

ObjectiveTo investigate whether the depletion of nerve growth factor (NGF) is associated with the development of chemotherapy-induced peripheral neuropathy (CIPN) in patients with hematologic malignancy.MethodsWe prospectively enrolled hematologic cancer patients who had a plan to receive bortezomib, thalidomide, or vincristine. Baseline NGF levels were measured within one week before the start date of chemotherapy. Follow-up NGF levels were measured after four months from the start date of chemotherapy or the date when CIPN was initially diagnosed.ResultsBaseline and follow-up NGF pairs were measured in 45 patients (male/female = 27/18, median age = 63 years old). CIPN has developed in 28 patients. In the CIPN group, the level of NGF was significantly decreased after chemotherapy compared to the baseline (△NGF = −3.52 ±5.72; p-value = 0.003), while the NGF level of the no-CIPN group was not changed after chemotherapy. The differences in △NGF levels between the CIPN and no-CIPN group were more profound when analyzed in the subgroup of newly diagnosed multiple myeloma patients (△NGF = −4.14 ± 4.87 pg/ml for the CIPN group and +2.52 ± 8.39 pg/ml for the no-CIPN group; p-value = 0.043).ConclusionsThis study shows that the depletion of NGF occurs during the development of CIPN, suggesting pathogenesis based on the role of NGF and therapeutic implications.

Highlights

  • Chemotherapy-induced peripheral neuropathy (CIPN) is one of the major complications of chemotherapy in hematologic malignancy, which deteriorates quality of life (QOL)[1]

  • In the CIPN group, the level of nerve growth factor (NGF) was significantly decreased after chemotherapy compared to the baseline (4NGF = −3.52 ±5.72; p-value = 0.003), while the NGF level of the no-CIPN group was not changed after chemotherapy

  • The differences in 4NGF levels between the CIPN and no-CIPN group were more profound when analyzed in the subgroup of newly diagnosed multiple myeloma patients (4NGF = −4.14 ± 4.87 pg/ml for the CIPN group and +2.52 ± 8.39 pg/ml for the noCIPN group; p-value = 0.043)

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Summary

Introduction

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the major complications of chemotherapy in hematologic malignancy, which deteriorates quality of life (QOL)[1]. It frequently causes distal sensory neuropathic pain, chronic general weakness and early discontinuation of chemotherapeutic agents, which can increase cancer-related morbidity and mortality [2, 3]. One of major neurotrophins is nerve growth factor (NGF), known to regulate the growth, maintenance, and survival of neurons[9, 10] This factor is trophic to small fiber neurons that dominate pain, temperature, and autonomic function[11]. Most previous CIPN studies related to NGF were limited to conventional cytotoxic agents

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