Rosenthal Seth A, Bae Kyoungwha, Pienta Kenneth J, Sobczak Mark L, Asbell Sucha O, Rajan Raghu, Kerlin Kevin J, Michalski Jeff M, Sandler Howard M
Radiation Oncology Center, Radiological Associates of Sacramento, Sacramento, CA 95815, USA.
Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):672-8. doi: 10.1016/j.ijrobp.2008.05.020. Epub 2008 Nov 5.
Long-term androgen suppression plus radiotherapy (AS+RT) is standard treatment of high-risk prostate cancer. A randomized trial, Radiation Therapy Oncology Group trial 9902, was undertaken to determine whether adjuvant chemotherapy with paclitaxel, estramustine, and etoposide (TEE) plus AS+RT would improve disease outcomes with acceptable toxicity.
High-risk (prostate-specific antigen 20-100 ng/mL and Gleason score >or=7; or Stage T2 or greater, Gleason score 8, prostate-specific antigen level <100 ng/mL) nonmetastatic prostate cancer patients were randomized to AS+RT (Arm 1) vs. AS+RT plus four cycles of TEE (Arm 2). TEE was delivered 4 weeks after RT. AS continued for 2 years for both treatment arms. RT began after 8 weeks of AS began.
The Radiation Therapy Oncology Group 9902 trial opened January 11, 2000. Excess thromboembolic toxicity was noted, leading to study closure October 4, 2004. A total of 397 patients were accrued, and the data for 381 were analyzable. An acute and long-term toxicity analysis was performed. The worst overall toxicities during treatment were increased for Arm 2. Of the 192 patients, 136 (71%) on Arm 2 had RTOG Grade 3 or greater toxicity compared with 70 (37%) of 189 patients on Arm 1. Statistically significant increases in hematologic toxicity (p < 0.0001) and gastrointestinal toxicity (p = 0.017) but not genitourinary toxicity (p = 0.07) were noted during treatment. Two Grade 5 complications related to neutropenic infection occurred in Arm 2. Three cases of myelodysplasia/acute myelogenous leukemia were noted in Arm 2. At 2 and 3 years after therapy completion, excess long-term toxicity was not observed in Arm 2.
TEE was associated with significantly increased toxicity during treatment. The toxicity profiles did not differ at 2 and 3 years after therapy. Toxicity is an important consideration in the design of trials using adjuvant chemotherapy for prostate cancer.
长期雄激素抑制联合放疗（AS+RT）是高危前列腺癌的标准治疗方法。开展了一项随机试验，即放射治疗肿瘤学组试验9902，以确定紫杉醇、雌莫司汀和依托泊苷（TEE）辅助化疗联合AS+RT是否能在可接受的毒性范围内改善疾病预后。
高危（前列腺特异性抗原20 - 100 ng/mL且Gleason评分≥7；或T2期及以上、Gleason评分8、前列腺特异性抗原水平<100 ng/mL）非转移性前列腺癌患者被随机分为AS+RT组（第1组）和AS+RT联合四个周期TEE组（第2组）。TEE在放疗后4周给予。两组治疗中雄激素抑制均持续2年。放疗在雄激素抑制开始8周后开始。
放射治疗肿瘤学组9902试验于2000年1月11日开启。发现血栓栓塞毒性过高，导致研究于2004年10月4日结束。共纳入397例患者，其中381例患者的数据可进行分析。进行了急性和长期毒性分析。第2组治疗期间最严重的总体毒性有所增加。在第2组的192例患者中，136例（71%）出现放射治疗肿瘤学组3级及以上毒性，而第1组189例患者中有70例（37%）出现该情况。治疗期间血液学毒性（p < 0.0001）和胃肠道毒性（p = 0.017）有统计学意义的显著增加，但泌尿生殖系统毒性（p = 0.07）无显著增加。第2组发生了2例与中性粒细胞减少感染相关的5级并发症。第2组发现3例骨髓发育异常/急性髓系白血病。在治疗完成后2年和3年，未观察到第2组有过多的长期毒性。
TEE与治疗期间毒性显著增加相关。治疗后2年和3年的毒性特征无差异。在设计前列腺癌辅助化疗试验时，毒性是一个重要的考虑因素。
