Neoadjuvant mitoxantrone and docetaxel for high-risk localized prostate cancer
Neoadjuvant mitoxantrone and docetaxel for high-risk localized prostate cancer
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DOI：
10.1016/j.urolonc.2005.11.034
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发表时间：
2006-05-01
影响因子：
2.7
通讯作者：
Beer, TM
中科院分区：
文献类型：
--
作者：
Garzotto, M;Myrthue, A;Beer, TM
目的：现有的治疗高危临床局限性前列腺癌的方法，由于局部或转移性肿瘤根治不彻底，实现肿瘤完全消除的机会有限。这项I/II期研究的目的是评估前列腺癌切除术前新辅助药物多西紫杉醇和米托蒽醌的安全性和有效性。材料和方法：22例高危临床局限性前列腺癌患者在前列腺癌切除术前每周接受多西紫杉醇(35 mg/m(2))治疗，同时增加米托蒽酮(2-5 mg/m(2))的剂量，共12个疗程，共16周。结果：米托蒽醌的最大耐受量为4 mg/m(2)，主要毒性为中性粒细胞减少症。在整个治疗过程中，睾丸激素水平保持不变。95%的患者PSA下降，中位数下降41%。手术在化疗后耐受性良好，没有任何重大并发症。76%的患者手术切缘为阴性。结论：在这一人群中，在前列腺切除术前给予多药化疗是安全的。这种疗法似乎具有抗肿瘤活性，在没有明显睾酮变化的情况下，PSA降低就是明证。由于患者或外科医生因素的影响不能从新辅助治疗的潜在影响中分离出来，所以在III期试验之外，不能确定化疗对提高手术切缘率的益处。在新佐剂环境中继续研究新的药物是有必要的，因为这种方法允许快速鉴定活性药物并对药物活性的机制进行分子研究。由爱思唯尔公司出版。
Purpose: Currently available treatment modalities for high-risk clinically localized prostate cancer have limited chances of achieving complete tumor elimination because of either inadequate local or metastatic tumor eradication. The goal of this phase I/II study is to evaluate the safety and efficacy of neoadjuvant docetaxel and mitoxantrone before prostatectomy.Materials and Methods: A total of 22 men with high-risk clinically localized prostate cancer underwent weekly treatment with docetaxel (35 mg/m(2)), with increasing doses of mitoxantrone (2-5 mg/m(2)) for a 12 of 16-week treatment cycle before prostatectomy. Testosterone and prostate-specific antigen (PSA) measurements were made before and after chemotherapy.Results: The maximally tolerated dose for mitoxantrone was 4 mg/m(2), and the primary toxicity was neutropenia. Testosterone levels were maintained throughout treatment. PSA reductions were observed in 95% of patients, with a median reduction of 41%. The surgery was well tolerated after chemotherapy, without any major complications. Negative surgical margins were attained in 76% of patients.Conclusions: Administration of multi-agent chemotherapy before prostatectomy was safe in this population. This regimen appeared to have antineoplastic activity as evidenced by PSA reductions in the absence of significant testosterone changes. The benefit of chemotherapy for improving surgical margin rates could not be determined outside of a phase III trial because the effect of patient or surgeon factors could not be dissected from the potential effect of neoadjuvant therapy. Continued study of novel agents in the neoadjuvant setting is warranted because this approach allows for the rapid identification of active agents and for molecular investigation into the mechanism of drug activity. Published by Elsevier Inc.