Garzotto Mark, Myrthue Anne, Higano Celestia S, Beer Tomasz M
Urology Section, Surgical Service, Portland VA Medical Center, Portland, OR 97239, USA.
Urol Oncol. 2006 May-Jun;24(3):254-9. doi: 10.1016/j.urolonc.2005.11.034.
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.
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.
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.
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.
由于局部肿瘤根除不充分或存在转移，目前用于治疗高危临床局限性前列腺癌的治疗方式实现肿瘤完全消除的机会有限。本I/II期研究的目的是评估前列腺切除术前行新辅助多西他赛和米托蒽醌治疗的安全性和有效性。
共有22例高危临床局限性前列腺癌男性患者在前列腺切除术前接受为期16周、共12周的治疗，每周接受多西他赛（35mg/m²）治疗，并递增米托蒽醌剂量（2 - 5mg/m²）。化疗前后进行睾酮和前列腺特异性抗原（PSA）测量。
米托蒽醌的最大耐受剂量为4mg/m²，主要毒性为中性粒细胞减少。整个治疗过程中睾酮水平维持稳定。95%的患者PSA水平降低，中位降低幅度为41%。化疗后手术耐受性良好，无任何严重并发症。76%的患者实现手术切缘阴性。
在该人群中，前列腺切除术前给予多药联合化疗安全。该方案似乎具有抗肿瘤活性，表现为PSA降低而睾酮无显著变化。由于无法将患者或外科医生因素的影响与新辅助治疗的潜在影响区分开来，因此在III期试验之外无法确定化疗对提高手术切缘率的益处。有必要继续在新辅助治疗环境中研究新型药物，因为这种方法能够快速识别活性药物，并对药物活性机制进行分子研究。
