Acetyl-L-carnitine (ALCAR) for the prevention of chemotherapy-induced peripheral neuropathy in patients with relapsed or refractory multiple myeloma treated with bortezomib, doxorubicin and low-dose dexamethasone: a study from the Wisconsin Oncology Network. Cancer Chemother Pharmacol 2014 Oct;74(4):875-82
Date
08/30/2014Pubmed ID
25168296Pubmed Central ID
PMC4175433DOI
10.1007/s00280-014-2550-5Scopus ID
2-s2.0-84919327424 (requires institutional sign-in at Scopus site) 29 CitationsAbstract
PURPOSE: Retreatment with bortezomib (B) is often considered for patients with relapsed multiple myeloma (MM), but this strategy is hindered by uncertainty of response and emergence of B-induced peripheral neuropathy (PN). We incorporated acetyl-L-carnitine (ALCAR) to prevent PN and allow for adequate dosing. We also investigated the correlation between B-inducible NF-κB activation and response to therapy.
METHODS: Nineteen patients with relapsed/refractory MM received up to 8 cycles of intravenous bortezomib, doxorubicin and oral low-dose dexamethasone (BDD) to evaluate response and toxicity. Thirteen additional patients received prophylactic ALCAR (BDD-A). Patients receiving BDD-A were evaluated by FACT-GOG-TX, FACIT-Fatigue, Neuropathic Pain index (NPI) and Grooved Pegboard (GP) testing. Primary MM cells from 11 patients were tested for B-inducible NF-κB activation.
RESULTS: Seventy-six percent of subjects were refractory to previous treatment, 39% refractory to bortezomib. Median cycles received were 5. CR + PR for the entire group were 53% and did not differ between groups. Incidence of ≥3 PN was 32% in the BDD group versus 15 % in the BDD-A group (p = ns). Patient-reported fatigue and PN measured by FACT-GOG-TX increased throughout the treatment period in the BDD-A group, although time to complete GP testing declined. In a sub-study examining constitutive bortezomib-inducible NF-κB activity in primary subject-specific MM cells, the presence of NF-κB activation correlated with lower likelihood of response.
CONCLUSIONS: Addition of ALCAR to BDD did not alter the incidence or severity of PN in relapsed MM patients receiving a B-based regimen. Bortezomib-inducible NF-κB activation in patient-derived primary MM cells may be associated with poorer response.
Author List
Callander N, Markovina S, Eickhoff J, Hutson P, Campbell T, Hematti P, Go R, Hegeman R, Longo W, Williams E, Asimakopoulos F, Miyamoto SAuthors
Peiman Hematti MD Professor in the Medicine department at Medical College of WisconsinWalter L. Longo MD Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AcetylcarnitineAntineoplastic Agents
Boronic Acids
Bortezomib
Dexamethasone
Doxorubicin
Drug Resistance, Neoplasm
Female
Humans
Male
Middle Aged
Multiple Myeloma
NF-kappa B
Neurologic Examination
Nootropic Agents
Peripheral Nervous System Diseases
Pyrazines
Recurrence
Severity of Illness Index
Treatment Outcome
