Lower Dose Dexamethasone/Thalidomide and Zoledronic Acid Every 3 Weeks in Previously Untreated Multiple Myeloma

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• 作者：Gerrard Teoh¹ ; ² ; ^{gkh_teoh@parkway.sg} ; Yuming Chen³ ; Kihyun Kim⁴ ; Alok Srivastava⁵ ; Vasant R. Pai⁶ ; Sung-Soo Yoon⁷ ; Cheolwon Suh⁸ ; Yeo-Kyeoung Kim⁹
• 关键词：Antimyeloma effect ; Asian patients ; Dexamethasone ; Thalidomide ; Zoledronic acid
• 刊名：Clinical Lymphoma Myeloma and Leukemia
• 出版年：2012
• 出版时间：April, 2012
• 年：2012
• 卷：12
• 期：2
• 页码：118-126
• 全文大小：626 K

文摘

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.

Patients and 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 Blad¨¦ 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.

Conclusion

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.