Tu S M, Pagliaro L C, Banks M E, Amato R J, Millikan R E, Bugazia N A, Madden T, Newman R A, Logothetis C J
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Clin Cancer Res. 1998 May;4(5):1193-201.
In this study, we determined the maximum tolerated plasma concentration of suramin (within the predetermined study target range) when combined with doxorubicin in the treatment of androgen-independent prostate cancer. Twenty-four patients received suramin dosages based on proportional adjustment of the steady-state plasma suramin concentration to achieve the targeted plasma concentrations of 50-100, 101-150, 151-200, or 201-250 microg/ml. Doxorubicin (20 mg/m2) was administered i.v. over 24 h at weekly intervals. Suramin was given i.v. over 2 h twice weekly. Patients received treatment until dose-limiting toxicity or disease progression. Side effects similar to those reported for suramin and doxorubicin administered as individual agents were observed. Dose-limiting motor neuropathy developed in three patients (13%). Twelve of 24 evaluable patients (50%; 95% confidence interval, 28-71%) and 6 of 10 evaluable patients (60%; 95% confidence interval, 26-88%) had a >50% decrease of prostate-specific antigen and measurable lesions, respectively. The maximum tolerated plasma level of suramin when combined with doxorubicin was 151-200 microg/ml. Future studies on suramin combined with doxorubicin or other agents could be performed using a fixed dosing scheme with a targeted suramin steady-state plasma concentration of 200 microg/ml.
在本研究中，我们确定了苏拉明与阿霉素联合用于治疗雄激素非依赖性前列腺癌时的最大耐受血浆浓度（在预定的研究目标范围内）。24例患者根据稳态血浆苏拉明浓度的比例调整接受苏拉明剂量，以达到50 - 100、101 - 150、151 - 200或201 - 250μg/ml的目标血浆浓度。阿霉素（20mg/m²）静脉滴注，24小时内给药，每周一次。苏拉明每周两次，静脉滴注2小时。患者接受治疗直至出现剂量限制性毒性或疾病进展。观察到的副作用与单独使用苏拉明和阿霉素时报告的副作用相似。3例患者（13%）出现剂量限制性运动神经病变。24例可评估患者中有12例（50%；95%置信区间，28 - 71%）前列腺特异性抗原下降>50%，10例可评估患者中有6例（60%；95%置信区间，26 - 88%）有可测量病变缩小。苏拉明与阿霉素联合使用时的最大耐受血浆水平为151 - 200μg/ml。未来关于苏拉明与阿霉素或其他药物联合使用的研究可采用固定给药方案，使苏拉明稳态血浆浓度目标为200μg/ml。
