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

作者：Callander Natalie^*; Markovina Stephanie; Eickhoff Jens; Hutson Paul; Campbell Toby; Hematti Peiman; Go Ronald; Hegeman Robert; Longo Walter; Williams Eliot; Asimakopoulos Fotis; Miyamoto Shigeki

来源：Cancer Chemotherapy and Pharmacology, 2014, 74(4): 875-882.

DOI：10.1007/s00280-014-2550-5

• Multiple myeloma
• Bortezomib
• Neuropathy
• Acetyl-L-carnitine
• NF-kB

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-kappa B activation and response to therapy.
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-kappa B activation.
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 a parts per thousand yen3 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-kappa B activity in primary subject-specific MM cells, the presence of NF-kappa B activation correlated with lower likelihood of response.
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-kappa B activation in patient-derived primary MM cells may be associated with poorer response.

• 出版日期2014-10