Vorinostat plus bortezomib for the treatment of relapsed/refractory multiple myeloma: a case series illustrating utility in clinical practice.
BACKGROUND
Increasing numbers of patients are presenting with relapsed/refractory multiple myeloma (MM) following treatment with bortezomib. Therefore, there is a need for effective and well-tolerated treatment strategies after failure of bortezomib-based regimens. Vorinostat, a histone deacetylase inhibitor, has demonstrated antiproliferative and proapoptotic activity alone and in combination with bortezomib in preclinical models of MM. Preliminary results from ongoing phase I trials have demonstrated the clinical activity of vorinostat in combination with bortezomib in patients with MM. This case series reports our experience of combined vorinostat and bortezomib in 6 patients with relapsed/refractory MM after previous bortezomib.


METHODS
Patients received oral vorinostat 300 mg or 400 mg once daily (days 1-14) and bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 in a 21-day cycle.


RESULTS
All patients derived clinical benefit from combined vorinostat and bortezomib, with objective response observed in 5 of the 6 patients (> or = minimal response), including 1 very good partial response; stable disease was observed in the remaining patient. Patients remained on therapy until disease progression. Combined vorinostat and bortezomib therapy was well tolerated: grade 2 nausea and diarrhea were the only adverse events reported. No patients discontinued therapy because of toxicity, and no dose adjustments were required for either agent.


CONCLUSIONS
These results suggest that combined vorinostat and bortezomib therapy is effective in patients with relapsed/refractory MM after failure of previous bortezomib-based regimens and support further evaluation of this combination in randomized trials.
Mazumder
Amitabha
A
St Vincent's Comprehensive Cancer Center, New York, NY 10011, USA. amazumder@aptiumoncology.com
Vesole
David H
DH
Jagannath
Sundar
S
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001897:Boronic Acids; D000069286:Bortezomib; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D018450:Disease Progression; D005260:Female; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000209:etiology; D011719:Pyrazines; D012008:Recurrence; D000077337:Vorinostat
D000970:Antineoplastic Agents; D001897:Boronic Acids; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011719:Pyrazines; D000077337:Vorinostat; D000069286:Bortezomib