Manni A, Santen R J, Boucher A E, Lipton A, Harvey H, Simmonds M, White-Hershey D, Gordon R A, Rohner T, Drago J
Anticancer Res. 1986 Mar-Apr;6(2):309-14.
We report here in the interim analysis of an ongoing randomized clinical trial designed to test whether androgen priming enhances tumor chemosensitivity in men with stage D prostate cancer refractory to orchiectomy. All patients are continuously treated with aminoglutethimide and hydrocortisone, to lower adrenal androgen secretion, and are given cyclic chemotherapy. Patients in the stimulation arm receive also the synthetic androgen, fluoxymesterone, for 3 days before and on the day of chemotherapy. Of 57 patients entered to date, 41 have received adequate treatment to be evaluable. Response to therapy (objective remissions + stabilizations of disease) occurred in 17 of 18 evaluable patients (94%) randomized to the stimulation arm, and in 16 of 23 evaluable patients (70%) in the control group (p less than 0.025). Duration of response was not significantly different in the two groups (median: 9 months in the stimulation and 12 months in the control arm). With 30% of the total of 57 patients still alive, survival is not significantly different in the stimulation (median: 13 months) and control arm (median: 16 months). As expected, patients who responded to treatment lived significantly longer than those who failed to benefit. Two episodes of reversible spinal cord compression occurred during androgen administration. (The risk of this serious side effect may be reduced by performing a screening myelogram to rule out subclinical spinal metastasis). Our preliminary data suggest that androgen priming may enhance the tumoricidal effect of cytotoxic drugs in advanced prostate cancer. The lack of improvement in duration of response and survival may be explained by the large fraction of hormone-independent cells probably present in patients with tumors refractory to orchiectomy.
我们在此报告一项正在进行的随机临床试验的中期分析，该试验旨在测试雄激素预处理是否能增强对睾丸切除术难治的D期前列腺癌男性患者的肿瘤化疗敏感性。所有患者均持续接受氨鲁米特和氢化可的松治疗，以降低肾上腺雄激素分泌，并接受周期性化疗。刺激组的患者在化疗前3天及化疗当天还接受合成雄激素氟甲睾酮治疗。在迄今入组的57例患者中，41例接受了足够的治疗可进行评估。随机分配至刺激组的18例可评估患者中有17例（94%）对治疗有反应（客观缓解+疾病稳定），而对照组23例可评估患者中有16例（70%）有反应（p<0.025）。两组的反应持续时间无显著差异（中位数：刺激组为9个月，对照组为12个月）。57例患者中30%仍存活，刺激组（中位数：13个月）和对照组（中位数：16个月）的生存率无显著差异。正如预期的那样，对治疗有反应的患者存活时间明显长于未受益的患者。在雄激素给药期间发生了2例可逆性脊髓压迫。（通过进行筛查性脊髓造影以排除亚临床脊柱转移，可能会降低这种严重副作用的风险）。我们的初步数据表明，雄激素预处理可能会增强细胞毒性药物对晚期前列腺癌的杀瘤作用。反应持续时间和生存率缺乏改善可能是由于对睾丸切除术难治的肿瘤患者中可能存在大量激素非依赖性细胞所致。
