The frequency, characteristics and reversibility of bortezomib-associated peripheral neuropathy were evaluated in the phase III APEX (Assessment of Proteasome Inhibition for Extending Remissions) trial in patients with relapsed myeloma, and the impact of a dose-modification guideline on peripheral neuropathy severity and reversibility was assessed. Patients received bortezomib 1·3 mg/m2 (days 1, 4, 8, 11, eight 21-d cycles, then days 1, 8, 15, 22, three 35-d cycles); bortezomib was held, dose-reduced or discontinued depending on peripheral neuropathy severity, according to a protocol-specified dose-modification guideline. Overall, 124/331 patients (37%) had treatment-emergent peripheral neuropathy, including 30 (9%) with grade ≥3; incidence and severity were not affected by age, number/type of prior therapies, baseline glycosylated haemoglobin level, or diabetes history. Grade ≥3 incidence appeared lower versus phase II trials (13%) that did not specifically provide dose-modification guidelines. Of patients with grade ≥2 peripheral neuropathy, 58/91 (64%) experienced improvement or resolution to baseline at a median of 110 d, including 49/72 (68%) who had dose modification versus 9/19 (47%) who did not. Efficacy did not appear adversely affected by dose modification for grade ≥2 peripheral neuropathy. Bortezomib-associated peripheral neuropathy is manageable and reversible in most patients with relapsed myeloma. Dose modification using a specific guideline improves peripheral neuropathy management without adversely affecting outcome.

Additional Metadata
Keywords Bortezomib, Dose modification, Multiple myeloma, Peripheral neuropathy, Relapsed, Vinca alkaloid, adult, alkylating agent, anthracycline derivative, article, bortezomib, cancer relapse, carnitine, controlled study, disease severity, drug dose reduction, drug dose regimen, drug efficacy, drug withdrawal, duloxetine, folic acid, gabapentin, glycosylated hemoglobin, human, major clinical studymajor clinical study, motor neuropathy, multiple cycle treatment, multiple myeloma, nortriptyline, nutritional support, peripheral neuropathy, practice guideline, priority journal, recommended drug dose, sensory neuropathy, thalidomide, thioctic acid, treatment outcome, vitamin, vitamin B complex
Persistent URL dx.doi.org/10.1111/j.1365-2141.2008.07573.x, hdl.handle.net/1765/18326
Citation
Richardson, P.G., Sonneveld, P., Schuster, M.W., Stadtmauer, E.A., Facon, T., Harousseau, J-L., … San Miguel, J-F.. (2009). Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX trial in relapsed multiple myeloma: Impact of a dose-modification guideline. British Journal of Haematology, 144(6), 895–903. doi:10.1111/j.1365-2141.2008.07573.x