Lower dose dexamethasone/thalidomide and zoledronic acid every 3 weeks in previously untreated multiple myeloma.
BACKGROUND
Physicians in Asia have anecdotally reported that Asian patients with multiple myeloma (MM) are frequently intolerant of conventional doses of dexamethasone (Dex) and/or thalidomide (Thal). Since zoledronic acid (Zol) has an anti-MM effect in preclinical studies, we investigated whether the approved 3-times-weekly Zol combined with lower dose Dex/Thal could be an effective and better tolerated regimen in Asian patients.


METHODS
In this first Asian cooperative multicenter phase II study, previously untreated patients with MM (N = 44) received up to 6 cycles of 3-times-weekly low-dose Dex/Thal and 4 mg Zol (the dtZ regimen). Response was graded using Bladé criteria.


RESULTS
The average doses of Dex and Thal administered were 185.2 mg/month; and 87.5 mg/day, respectively. Thirty-nine (88.6%) patients demonstrated at least a partial response (PR), including 18.2% very good partial response (VGPR), 15.9% near complete response (nCR) and 18.2% complete response (CR). Achievement of CR/nCR was related to significant (P < .05), rapid, and sustained inhibition of osteoclasts (OCs) and OC precursors (pOCs) by Zol. Sepsis was the most frequently reported serious toxicity, contributing to 3 of 4 deaths. Importantly, there was no peripheral neuropathy, osteonecrosis of the jaw, or nephrotoxicity.


CONCLUSIONS
We conclude that the dtZ regimen is an effective and well-tolerated regimen for Asian patients with newly diagnosed MM. The high rate of VGPR/nCR/CR suggests that Zol could have a clinically relevant anti-MM effect. Since infections are the most frequent adverse event, it is probably wise to further lower the dose of Dex in future studies.
Gleneagles Hospital, Singapore, Republic of Singapore. gkh_teoh@parkway.sg
Gerrard
G
Teoh
Yuming
Y
Chen
Kihyun
K
Kim
Alok
A
Srivastava
Vasant R
VR
Pai
Sung-Soo
SS
Yoon
Cheolwon
C
Suh
Yeo-Kyeoung
YK
Kim
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage; D004164:Diphosphonates / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D013792:Thalidomide / Q000008:administration & dosage; D016896:Treatment Outcome; D000077211:Zoledronic Acid
D004164:Diphosphonates; D007093:Imidazoles; D013792:Thalidomide; D000077211:Zoledronic Acid; D003907:Dexamethasone