Amin Asim, Halabi Susan, Gelmann Edward P, Stadler Walter, Vogelzang Nicholas, Small Eric
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
Urol Oncol. 2004 Sep-Oct;22(5):398-403. doi: 10.1016/j.urolonc.2004.05.002.
Institution of early hormone therapy in the PSA era coupled with demonstration of clinical benefit with chemotherapy in hormone refractory prostate cancer (HRPC) and acceptance of PSA decline as a surrogate for response has resulted in introduction of chemotherapy earlier in the natural history of disease. There now exists a need to identify, effective agents for second line chemotherapy. 9-nitrocamptothecin (9-NC) a novel, oral camptothecin analogue was tested as second line chemotherapy for patients with progressive hormone refractory prostate cancer.
Eligible patients had metastatic hormone refractory prostate cancer with performance status (0-1) following progression on at least 1 prior cytotoxic chemotherapy. 9-NC was administered orally at the dose of 1.5 mg/m2/d for 5 days each week for 3 weeks, followed by rest for 1 week. Response was evaluated after 2 cycles according to the guidelines set forth for Phase II trials in HRPC by the PSA working group.
Thirty-five patients were recruited to the study within a period of 6 months; 33 were evaluable for analysis. No patients had a >50% decline in PSA levels. Two out of 8 (25%) patients with measurable disease and 5/25 (20%) patients with nonmeasurable disease showed stable disease. The median time to disease and PSA progression was 2 months [95% confidence interval (CI), 0.9-2.8]. The median overall survival was 10 months (95% CI = 5-12). Seven patients are alive after a median follow-up of 23 months.
9-nitrocamptothecin failed to elicit clinical or PSA responses. Further study in pretreated HRPC patients is not warranted.
在前列腺特异性抗原（PSA）时代，早期激素治疗的应用，以及激素难治性前列腺癌（HRPC）化疗临床获益的证实，加上将PSA下降作为反应替代指标的认可，导致在疾病自然史中更早地引入化疗。现在需要确定二线化疗的有效药物。9-硝基喜树碱（9-NC）是一种新型口服喜树碱类似物，被作为二线化疗药物用于治疗进展性激素难治性前列腺癌患者。
符合条件的患者为转移性激素难治性前列腺癌，在至少1次先前的细胞毒性化疗进展后，其体能状态为（0-1）。9-NC口服给药，剂量为1.5mg/m²/天，每周5天，共3周，随后休息1周。根据PSA工作组为HRPC的II期试验制定的指南，在2个周期后评估反应。
在6个月内招募了35例患者进行研究；33例可进行分析。没有患者的PSA水平下降超过50%。8例（25%）可测量疾病患者中有2例，25例（20%）不可测量疾病患者中有5例病情稳定。疾病和PSA进展的中位时间为2个月[95%置信区间（CI），0.9-2.8]。中位总生存期为10个月（95%CI=5-12）。中位随访23个月后，7例患者仍存活。
9-硝基喜树碱未能引起临床或PSA反应。不建议对先前接受过治疗的HRPC患者进行进一步研究。
