Falcone A, Antonuzzo A, Danesi R, Allegrini G, Monica L, Pfanner E, Masi G, Ricci S, Del Tacca M, Conte P
U.O. Oncologia Medica, Ospedale S. Chiara, Pisa, Italy.
Cancer. 1999 Aug 1;86(3):470-6. doi: 10.1002/(sici)1097-0142(19990801)86:3<470::aid-cncr15>3.0.co;2-7.
Suramin and epirubicin are both active agents in the treatment of patients with hormone-refractory advanced prostate carcinoma, with demonstrated antitumor synergism in vitro on human prostate carcinoma cells and different dose-limiting toxicities. The authors conducted this Phase II study to determine the feasibility, toxicity, and antitumor activity of suramin in combination with epirubicin.
Only patients with hormone-independent advanced prostate carcinoma who had progressive disease after the last therapeutic maneuver they had undergone, including antiandrogen withdrawal, entered the study. Suramin was administered initially as a 6-day continuous infusion for 10 consecutive weeks and then for 6 days every 28 days for a maximum of 6 months. Doses were determined by a computer-assisted dosing system that used Bayesian pharmacokinetics to maintain suramin plasma concentrations of 200-250 microg/mL. Cortisone acetate 25 mg, administered at 8 a.m. and 8 p.m. daily, was begun 4 weeks after the initiation of suramin therapy. Epirubicin 25 mg/m2 was given as a weekly intravenous bolus beginning on Day 1 and was continued for a maximum of 6 months.
Twenty-six patients entered the study. Toxicities mainly included World Health Organization Grade 1-2 nausea, fatigue, anorexia, neutropenia, peripheral neuropathy, creatinine elevation, proteinuria, and prolonged prothrombin time, whereas Grade 3 toxicities were uncommon. Among 11 patients with measurable disease, 3 (27%) demonstrated an objective response. Among 24 patients evaluated for prostate specific antigen (PSA) response, 8 (33%; 95% confidence interval 16-55%) had a > or =50% decrease in PSA levels, which lasted a median of 32 (range, 8-52) weeks. Median progression free and overall survival were both 8 months.
The combination of suramin and epirubicin used in the current study is feasible, is associated with moderate toxicities, and has antitumor activity in advanced hormone-refractory prostate carcinoma. However, the results obtained with this combination do not represent major improvements in the treatment of patients with this disease, compared with suramin or epirubicin alone or other available treatments.
舒拉明和表柔比星均为治疗激素难治性晚期前列腺癌患者的有效药物，在体外对人前列腺癌细胞具有抗肿瘤协同作用，且有不同的剂量限制性毒性。作者开展了这项II期研究，以确定舒拉明联合表柔比星的可行性、毒性及抗肿瘤活性。
仅纳入那些在接受包括抗雄激素撤药在内的最后一次治疗后病情仍进展的激素非依赖性晚期前列腺癌患者进入本研究。舒拉明最初连续6天静脉输注，共10周，之后每28天输注6天，最长6个月。剂量由计算机辅助给药系统确定，该系统采用贝叶斯药代动力学维持舒拉明血浆浓度在200 - 250μg/mL。舒拉明治疗开始4周后，每天上午8点和晚上8点给予25mg醋酸可的松。表柔比星25mg/m²从第1天开始每周静脉推注，最长持续6个月。
26例患者进入研究。毒性主要包括世界卫生组织1 - 2级恶心、疲劳、厌食、中性粒细胞减少、周围神经病变、肌酐升高、蛋白尿和凝血酶原时间延长，3级毒性不常见。在11例可测量疾病的患者中，3例（27%）表现出客观缓解。在24例评估前列腺特异性抗原（PSA）反应的患者中，8例（33%；95%置信区间16 - 55%）PSA水平下降≥50%，持续时间中位数为32周（范围8 - 52周）。无进展生存期和总生存期的中位数均为8个月。
本研究中使用的舒拉明联合表柔比星方案可行，毒性中等，对晚期激素难治性前列腺癌具有抗肿瘤活性。然而，与单独使用舒拉明或表柔比星或其他现有治疗方法相比，该联合方案在治疗该疾病患者方面未显示出重大改善。
