Matsuda H, Nonomura K, Nagamori S, Shinohara N, Koyanagi T, Maru A, Matsuno T, Fujieda J, Minami S, Morita H
Department of Urology, Hokkaido University School of Medicine.
Nihon Hinyokika Gakkai Zasshi. 1995 Oct;86(10):1530-7. doi: 10.5980/jpnjurol1989.86.1530.
We conducted a multicentric randomized trial to compare bilateral orchiectomy versus bilateral orchiectomy plus etoposide or estramustine phosphate as first-line therapy for advanced prostatic cancer (stage D2).
From January 1991 to December 1992 a total of 46 newly diagnosed cases (registered cases) of advanced (stage D2) prostatic cancer was randomized into 3 groups as follows; Group A: bilateral orchiectomy and 25 mg/day of etoposide every 2 weeks for 6 months. Group B: bilateral orchiectomy and 560 mg/day of estramustine phosphate for 6 months. Group C: bilateral orchiectomy alone. One of group A and one of group B were ineligible cases, so 44 were eligible. In the eligible cases, ages were ranged from 54 to 90 (mean of 71.2) years old. No significant difference of patients' characteristics was found among 3 groups and median follow-up period was 25 months. Response was evaluated based on the response criteria according to Japanese urological association. Specifically, a central pathologist who blinded to the treatment was employed for evaluating pathological response at six months.
Of the 44 eligible patients, 33 and 25 were evaluated for clinically and pathological analyses, respectively. Clinical response rates were 80% (12/15) of group A, 100% (4/4) of group B and 78.6% (11/14) of group C. No significant difference in the clinical response and survival rate was shown among the three groups. Significantly higher frequencies of side effects were noted in the grop B compared to the other two groups (p < 0.05) and cardiovascular complications were the most frequent in group B. Favorable pathological response was obtained in all of group B, but not statistically significant compared with 7/21 (33.3%) of response rate in group A and C. The pathological response was significantly correlated with the clinical one in all patients (p < 0.01). While 8 of 11 patients (73%) with pathological response grade 1, 2 and 3 achieved clinical PR (partial response) or CR (complete response), only 5 of 14 (36%) with grade 0 received PR or CR.
We conclude that low dose administration of etoposide or estramustine phosphate dose not improve clinical response and survival in a short term in castrated patients, but increases the adverse effects due to the drugs in these patients. In addition, the pathological evaluation at 6 months after treatment appears to reflect the clinical response at that time in newly diagnosed patients with advanced prostatic cancer.
我们进行了一项多中心随机试验，比较双侧睾丸切除术与双侧睾丸切除术加依托泊苷或磷酸雌莫司汀作为晚期前列腺癌（D2期）一线治疗的效果。
1991年1月至1992年12月，共46例新诊断的晚期（D2期）前列腺癌病例（登记病例）被随机分为3组，如下：A组：双侧睾丸切除术，每2周给予25mg/天依托泊苷，持续6个月。B组：双侧睾丸切除术，每天给予560mg磷酸雌莫司汀，持续6个月。C组：仅行双侧睾丸切除术。A组和B组各有1例不符合入选标准，因此有44例符合标准。在符合标准的病例中，年龄范围为54至90岁（平均71.2岁）。三组患者的特征无显著差异，中位随访期为25个月。根据日本泌尿外科学会的反应标准评估反应。具体而言，由一位对治疗不知情的中心病理学家在6个月时评估病理反应。
44例符合标准的患者中，分别有33例和25例接受了临床和病理分析。临床缓解率为：A组80%（12/15），B组100%（4/4），C组78.6%（11/14）。三组之间的临床反应和生存率无显著差异。与其他两组相比，B组的副作用发生率显著更高（p<0.05），且心血管并发症在B组中最为常见。B组所有患者均获得了良好的病理反应，但与A组和C组7/21（33.3%）的反应率相比无统计学意义。所有患者的病理反应与临床反应显著相关（p<0.01）。病理反应为1、2和3级的11例患者中有8例（73%）达到临床PR（部分缓解）或CR（完全缓解），而病理反应为0级的14例患者中只有5例（36%）达到PR或CR。
我们得出结论，在去势患者中，低剂量给予依托泊苷或磷酸雌莫司汀在短期内并不能改善临床反应和生存率，但会增加这些患者因药物导致的不良反应。此外，治疗后6个月的病理评估似乎反映了新诊断的晚期前列腺癌患者当时的临床反应。
