Development of Neuropathy in Patients With Myeloma Treated With Thalidomide: Patterns of Occurrence and the Role of Electrophysiologic Monitoring
- 20 September 2006
- journal article
- clinical trial
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 24 (27) , 4507-4514
- https://doi.org/10.1200/jco.2006.05.6689
Abstract
Purpose Peripheral neuropathy frequently limits the duration of treatment with thalidomide for patients with multiple myeloma. We assessed the time course of occurrence, possible predictive factors, and the utility of serial nerve electrophysiological studies (NES) for detecting onset of neuropathy. Patients and Methods Seventy-five patients with relapsed/refractory myeloma were enrolled onto a multicenter trial of dose-escalating thalidomide with or without interferon. Patients underwent clinical assessment plus NES at baseline and every 3 months. Time to development of neuropathy according to clinical or NES criteria was compared. Patient and treatment-related factors were compared as predictors of neuropathy. Results Thirty-nine percent had some NES abnormalities at baseline. Patients received thalidomide at a median dose-intensity of 373 mg/d. Thirty-one of 75 patients (41%) developed neuropathy during thalidomide treatment; 11 patients (15%) discontinued treatment with thalidomide due to neuropathy. The actuarial incidence of neuropathy increased from 38% at 6 months to 73% at 12 months, with 81% of responding patients developing this complication. Serial NES did not reliably predict the imminent development of clinical neuropathy requiring thalidomide cessation, nor were patient age, sex, or prior therapy predictive. Patients who developed neuropathy had a longer duration of thalidomide exposure (median, 268 v 89 days; P = .0001). Cumulative dose or dose-intensity received was not predictive. Conclusion The majority of patients will develop peripheral neuropathy given sufficient length of treatment with thalidomide. To minimize the risk of neurotoxicity, therapy should be limited to less than 6 months. Electrophysiologic monitoring provides no clear benefit versus careful clinical evaluation for the development of clinically significant neuropathy.Keywords
This publication has 31 references indexed in Scilit:
- Toxic neuropathyCurrent Opinion in Neurology, 2005
- Bortezomib or High-Dose Dexamethasone for Relapsed Multiple MyelomaNew England Journal of Medicine, 2005
- Thalidomide neurotoxicityNeurology, 2004
- Thalidomide sensory neurotoxicityNeurology, 2004
- A Phase 2 Study of Bortezomib in Relapsed, Refractory MyelomaNew England Journal of Medicine, 2003
- Thalidomide-Induced Neuropathy: In ResponseMayo Clinic Proceedings, 2002
- Thalidomide-induced neuropathyNeurology, 2002
- Molecular mechanisms of novel therapeutic approaches for multiple myelomaNature Reviews Cancer, 2002
- Incidence and Risk Factors for Thalidomide Neuropathy: a Prospective Study of 135 Dermatologic PatientsJournal of Investigative Dermatology, 2002
- Thalidomide in CancerBioDrugs, 2001