Khil M S, Kim J H, Bricker L J, Cerny J C
Department of Radiation Oncology, Henry Ford Hospital, Detroit, MI 48202, USA.
Cancer J Sci Am. 1997 Sep-Oct;3(5):289-96.
A prospective phase II study was carried out to determine whether estramustine phosphate (EMP) plus vinblastine (VBL) in combination with radiotherapy (RT) would improve the control of locally advanced prostate cancer. The rationale for combining EMP plus VBL with RT was based on the clinical and radiobiological data that EMP plus VBL acted as an excellent radiation sensitizer in cultured human prostatic carcinoma cells with the property of tissue selectivity. The combined EMP and VBL were well tolerated in the phase II clinical study of patients with advanced prostate cancer.
Between January 1991 and July 1996, 65 patients, stage T2 (B2) through stage T4 (D1), were entered into the study. Gleason pattern scores ranged from 4 to 10. Pretreatment prostate-specific antigen (PSA) was as follows: < 20 in 21 patients (32%), 20 to 50 in 23 patients (35%), and > 50 in 21 patients (32%). The median age was 70 years (55-83). All patients were treated with megavoltage beam radiation with a total tumor dose of 65 to 70 Gy. Oral EMP 450 mg/m2 daily and VBL 3 mg/m2 weekly were given concomitantly in 46 patients during the 7- to 7 1/2-week course of radiotherapy.
All patients showed prompt and complete tumor regression on digital rectal examination at 6 weeks following the completion of treatment. Median follow-up time is 43 months (3-65). PSA fell to an undetectable level by 6 weeks in 56 of 65 patients (86%). For the whole group at 5 years clinical control was 81%, but biochemical control (PSA < 4 ng/mL) was 48%. The likelihood of being free of biochemical relapse at 5 years was a function of initial PSA value (PSA < 20 in 64% of the cases, 21-50 in 60%, and > 50 in 0%). The biochemical-relapse-free survival at 5 years for each stage was T2, 49%; T3, 38%; and T4, 17%. In particular, a group of patients with pretreatment PSA levels of 20 to 50 ng/mL responded quite favorably to the present combined regimen in that only 40% of the patients showed a biochemical failure at 5 years, considering the high level of initial PSA.
The present combined approach is effective in achieving a high rate of tumor control with no disproportionately enhanced side effects. The rapid regression of the tumor nodules and sustained freedom from biochemical relapse suggest excellent long-term tumor control, especially in the group of patients with pretreatment PSA levels of 20 to 50 ng/mL.
开展一项前瞻性II期研究，以确定磷酸雌莫司汀（EMP）加长春碱（VBL）联合放疗（RT）是否能改善局部晚期前列腺癌的控制情况。EMP加VBL与RT联合使用的理论依据基于临床和放射生物学数据，即EMP加VBL在培养的人前列腺癌细胞中作为一种出色的辐射增敏剂，具有组织选择性。在晚期前列腺癌患者的II期临床研究中，EMP和VBL联合使用耐受性良好。
1991年1月至1996年7月，65例T2（B2）期至T4（D1）期患者进入该研究。Gleason分级评分范围为4至10分。治疗前前列腺特异性抗原（PSA）情况如下：21例患者（32%）<20，23例患者（35%）为20至50，21例患者（32%）>50。中位年龄为70岁（55 - 83岁）。所有患者均接受兆伏级射线放疗，总肿瘤剂量为65至70 Gy。46例患者在为期7至7.5周的放疗过程中，同时每日口服EMP 450 mg/m²，每周静脉注射VBL 3 mg/m²。
所有患者在完成治疗后6周时，直肠指检显示肿瘤迅速完全消退。中位随访时间为43个月（3 - 65个月）。65例患者中有56例（86%）在6周时PSA降至检测不到的水平。整个组5年时临床控制率为81%，但生化控制率（PSA<4 ng/mL）为48%。5年无生化复发的可能性是初始PSA值的函数（PSA<20的病例中为64%，21 - 50的病例中为60%，>50的病例中为0%）。各期5年无生化复发生存率分别为：T2期，49%；T3期，38%；T4期，17%。特别是，一组治疗前PSA水平为20至50 ng/mL的患者对当前联合治疗方案反应良好，考虑到初始PSA水平较高，5年时只有40%的患者出现生化失败。
目前的联合治疗方法能有效实现高肿瘤控制率，且副作用无不成比例增加。肿瘤结节迅速消退且持续无生化复发表明长期肿瘤控制良好，尤其是在治疗前PSA水平为20至50 ng/mL的患者组中。
