Reese D M, Tchekmedyian S, Chapman Y, Prager D, Rosen P J
Division of Hematology-Oncology and Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, CA, USA.
Invest New Drugs. 1998;16(4):353-9. doi: 10.1023/a:1006120910380.
Irinotecan is a DNA topoisomerase I inhibitor that has a wide spectrum of activity against human tumors in both preclinical and clinical studies. To evaluate the efficacy of irinotecan in hormone-refractory prostate cancer, we conducted a phase II study in 15 men with metastatic, PSA-progressive disease after primary androgen deprivation. Irinotecan was administered at a dose of 125 mg/m2 weekly for four weeks followed by a two-week rest period; cycles were repeated every six weeks. Response was assessed by evaluation of serial changes in the serum PSA. None of fifteen patients had a decline in PSA of greater than 50%; eight patients had stable disease as a best response. None of three patients with measurable disease had a partial or complete response. Toxicity was primarily hematologic and gastrointestinal, with 40% of patients requiring dose modification due to granulocytopenia and 20% requiring intravenous fluid supplementation after development of diarrhea. There were no treatment-related deaths. We conclude that irinotecan in the dose and schedule used in this trial does not have significant activity against hormone-refractory prostate cancer.
伊立替康是一种DNA拓扑异构酶I抑制剂，在临床前和临床研究中对人类肿瘤具有广泛的活性。为了评估伊立替康在激素难治性前列腺癌中的疗效，我们对15名在初次雄激素剥夺后出现转移性、前列腺特异性抗原（PSA）进展性疾病的男性患者进行了一项II期研究。伊立替康的给药剂量为125mg/m²，每周一次，共四周，随后休息两周；每六周重复一个周期。通过评估血清PSA的系列变化来评估反应。15名患者中没有一人的PSA下降超过50%；8名患者的最佳反应为疾病稳定。3名有可测量疾病的患者中没有一人有部分或完全反应。毒性主要是血液学和胃肠道方面的，40%的患者因粒细胞减少需要调整剂量，20%的患者在出现腹泻后需要补充静脉液体。没有与治疗相关的死亡。我们得出结论，本试验中使用的伊立替康剂量和方案对激素难治性前列腺癌没有显著活性。
