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Neurotoxicity of bortezomib therapy in multiple myeloma: a single-center experience and review of the literature Badros A; Goloubeva O; Dalal JS; Can I; Thompson J; Rapoport AP; Heyman M; Akpek G; Fenton RGCancer 2007[Sep]; 110 (5): 1042-9BACKGROUND: Bortezomib is active in heavily pretreated multiple myeloma patients; the dose-limiting toxicity is peripheral neuropathy (PN). METHODS: The authors retrospectively reviewed the incidence, severity, and risk factors for PN in 78 patients who received bortezomib. The median age was 57 years (range, 33-80 years), 62% of patients were men, and 37% of patients were African Americans. Seventeen patients (22%) had diabetes mellitus (DM), and 66 patients (85%) had received thalidomide. Before bortezomib treatment, 37% of the patients reported subjective, grade 1 or 2 PN. Patients received bortezomib alone (n = 10 patients) plus dexamethasone (n = 36 patients) and thalidomide (n = 20 patients) or chemotherapy (n = 12 patients). PN affected 52% of patients, including grade 3 and 4 PN in 15% and 7%, respectively. RESULTS: Twelve patients stopped bortezomib because of side effects that included PN (n = 9 patients), diarrhea (n = 2 patients) and cytomegalovirus pneumonia (n = 1 patient); 11 patients had dose reductions because of PN. Grade 4 PN affected 6 patients (sensory, n = 4 patients; motor/sensory, n = 2 patients). The onset of grade 4 PN was sudden rather than cumulative. Factors that were predictive of PN grade were baseline PN (P = .002), prior thalidomide use (P = .03), and the presence of DM (P = .03). Multiple myeloma responses included complete, near complete, and partial responses in 5% of patients, 10% of patients, and 27% of patients, respectively. Responses were independent of PN and of whether bortezomib was combined with chemotherapy or thalidomide. Patients remained on therapy longer for a median of 5 cycles (range, 2-36 cycles) when they received bortezomib plus thalidomide versus 3 cycles (range, 1-19 cycles) for the other combinations. PN therapy was mostly supportive. It was noteworthy that 6 of 9 patients with PN who received lenalidomide as salvage therapy after bortezomib had significant improvement in their symptoms. CONCLUSIONS: The risk of bortezomib-related PN was greater in patients who had PN and DM at baseline. The authors concluded that an unexpected, symptomatic improvement of PN on lenalidomide is worth further investigation.|Adult[MESH]|Aged[MESH]|Aged, 80 and over[MESH]|Antineoplastic Agents/adverse effects/therapeutic use[MESH]|Antineoplastic Combined Chemotherapy Protocols[MESH]|Boronic Acids/administration & dosage/*adverse effects/*therapeutic use[MESH]|Bortezomib[MESH]|Dexamethasone/administration & dosage[MESH]|Drug Administration Schedule[MESH]|Female[MESH]|Humans[MESH]|Male[MESH]|Middle Aged[MESH]|Multiple Myeloma/*drug therapy/pathology[MESH]|Neoplasm Recurrence, Local[MESH]|Peripheral Nervous System Diseases/*chemically induced[MESH]|Pyrazines/administration & dosage/*adverse effects/*therapeutic use[MESH]|Retrospective Studies[MESH]|Thalidomide/administration & dosage[MESH]|Treatment Outcome[MESH] |
