Lawton C A, Coleman C N, Buzydlowski J W, Forman J D, Marcial V A, DelRowe J D, Rotman M
Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee 53226, USA.
Int J Radiat Oncol Biol Phys. 1996 Oct 1;36(3):673-80. doi: 10.1016/s0360-3016(96)00336-7.
RTOG Protocol 90-20 was designed to evaluate the effect of the hypoxic cell sensitizer Etanidazole (SR-2508) on locally advanced adenocarcinoma of the prostate treated with concurrent external beam irradiation.
Patients with biopsy-proven adenocarcinoma of the prostate with locally advanced T2b, T3, and T4 tumors were eligible for this study. No patients with disease beyond the pelvis were eligible. Serum prostate specific antigen (PSA) was mandatory. All patients received definitive external beam irradiation using standard four-field whole pelvis treatment to 45-50 Gy, followed by a cone down with a minimum total dose to the prostate of 66 Gy at 1.8-2.0 Gy/fraction over 6.5-7.5 weeks. Etanidazole was delivered 1.8 g/m2 given 3 times a week to a total of 34.2 g/m2 or 19 doses.
Thirty-nine patients were entered onto the study. Three patients refused treatment; therefore, 36 patients were eligible for further evaluation. Median follow-up was 36.9 months from treatment end. All patients had elevated initial PSA levels, and 18 patients had PSAs of > 20 ng/ml. Tumor classification was T2, 12 patients (33.3%); T3, 22 patients (61.1%); and T4, 2 patients (5.6%). Complete clinical response, defined as PSA < 4 ng/ml and complete clinical disappearance, was attained in 17.9% of (5/28 pts) with information at 90 days and 56% of patients by 12 months following treatment. Relapse-free survival was 13% at 3 years with PSA < 4 ng/ml. There were no Grade 4 or 5 toxicities, either acute (during treatment) or in follow-up.
Results of this trial regarding PSA response and clinical disappearance of disease are similar to historical controls and do not warrant further investigation of etanidazole as was done in this trial. Drug toxicity that, in the past, has been unacceptably high with other hypoxic cell sensitizers does not appear to be a significant problem with this drug.
放射治疗肿瘤学组（RTOG）90 - 20方案旨在评估乏氧细胞增敏剂依他硝唑（SR - 2508）对接受同步外照射治疗的局部晚期前列腺腺癌的疗效。
经活检证实为前列腺腺癌且肿瘤为局部晚期T2b、T3和T4期的患者符合本研究条件。盆腔以外有疾病的患者不符合条件。血清前列腺特异性抗原（PSA）是必需的检查项目。所有患者均接受标准的四野全盆腔外照射，剂量为45 - 50 Gy，随后缩野，前列腺的最小总剂量为66 Gy，分6.5 - 7.5周给予，每次剂量为1.8 - 2.0 Gy。依他硝唑的给药剂量为1.8 g/m²，每周给药3次，总量为34.2 g/m²或19剂。
39例患者进入本研究。3例患者拒绝治疗；因此，36例患者符合进一步评估条件。从治疗结束起的中位随访时间为36.9个月。所有患者初始PSA水平均升高，18例患者的PSA > 20 ng/ml。肿瘤分类为T2期12例患者（33.3%）；T3期22例患者（61.1%）；T4期2例患者（5.6%）。定义为PSA < 4 ng/ml且临床完全消失的完全临床缓解，在90天时有信息的患者中为17.9%（5/28例），治疗后12个月时为56%的患者。3年时PSA < 4 ng/ml的无复发生存率为13%。无论是急性（治疗期间）还是随访期间，均无4级或5级毒性反应。
本试验关于PSA反应和疾病临床消失的结果与历史对照相似，不支持如本试验中那样对依他硝唑进行进一步研究。过去与其他乏氧细胞增敏剂相关的不可接受的高药物毒性，在这种药物中似乎不是一个重大问题。
