Randomized phase II study of two doses of gefitinib in hormone-refractory prostate cancer: A trial of the National Cancer Institute of Canada-Clinical Trials Group
Randomized phase II study of two doses of gefitinib in hormone-refractory prostate cancer: A trial of the National Cancer Institute of Canada-Clinical Trials Group
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DOI：
10.1200/jco.2005.02.129
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发表时间：
2005-01-20
影响因子：
45.3
通讯作者：
Seymour, L
中科院分区：
文献类型：
--
作者：
Canil, CM;Moore, MJ;Seymour, L
目的 表皮生长因子受体的过度表达已在晚期前列腺癌中得到证实，并与不良预后相关。加拿大国家癌症研究所临床试验组进行了一项多机构、随机、II 期研究，旨在评估两剂口服吉非替尼对症状轻微、激素难治性前列腺癌 (HRPC) 患者的疗效和毒性。 患者和方法 2001 年 7 月至 11 月期间，40 名患有 HRPC 且前列腺特异性抗原增加的患者 (PSA) 或可测量疾病进展且未接受过既往化疗的患者被随机分配至每天连续口服 250 mg (n = 19) 或 500 mg (n = 21) 吉非替尼组。主要终点是 PSA 反应率和客观可测量反应。在基线和治疗期间完成癌症治疗功能评估前列腺癌子量表 (FACT-P) 生活质量问卷。结果 没有患者表现出 PSA 或客观可测量的反应。 35 名可评估患者中，5 名 (14.3%) 具有稳定的 PSA（一名患者服用 250 mg，四名患者服用 500 mg），五名患者 (14.3%) 具有稳定疾病的最佳反应（持续时间为 2.5 至 16.8 个月）。未发现对 PSA 增加率有显着影响。观察到的最常见的药物相关非血液毒性是I至2级腹泻（250 mg，65%；500 mg，56%）、疲劳（250 mg，29%；500 mg，33%）和1至2级皮疹（250 mg，24%、500 mg，39%）。 FACT-P 评分在治疗期间下降，表明与基线相比症状恶化。结论 吉非替尼在任一剂量水平下均未导致 PSA 或客观可测量疾病的任何反应。吉非替尼在 HRPC 中具有最小的单药活性。 (C) 2005 年，美国临床肿瘤学会。
Purpose Overexpression of the epidermal growth factor receptor has been demonstrated in advanced prostate cancer and is associated with a poor outcome. A multi-institutional, randomized, phase II study was undertaken by the National Cancer Institute of Canada-Clinical Trials Group to evaluate the efficacy and toxicity of two doses of oral gefitinib in patients with minimally symptomatic, hormone-refractory prostate cancer (HRPC).Patients and Methods Between July and November 2001, 40 patients with HRPC and increasing prostate-specific antigen (PSA) or progression in measurable disease who had not received prior chemotherapy were randomly assigned to 250 mg (n = 19) or 500 mg (n = 21) oral gefitinib daily continuously. The primary end points were PSA response rate and objective measurable response. Functional Assessment of Cancer Therapy Prostate Cancer Subscale (FACT-P) quality-of-life questionnaires were completed at baseline and during treatment.Results None of the patients demonstrated a PSA or objective measurable response. Five (14.3%) of 35 assessable patients had stable PSA (one patient at 250 mg and four patients at 500 mg), and five patients (14.3%) had a best response of stable disease (duration, 2.5 to 16.8 months). No significant effect on the rate of increase in PSA was seen. The most common drug-related nonhematologic toxicities observed were grade I to 2 diarrhea (250 mg, 65%; 500 mg, 56%), fatigue (250 mg, 29%; 500 mg, 33%), and grade 1 to 2 skin rash (250 mg, 24%, 500 mg, 39%). FACT-P scores decreased during treatment, indicating worsening of symptoms compared with baseline.Conclusion Gefitinib did not result in any responses in PSA or objective measurable disease at either dose level. Gefitinib has minimal single-agent activity in HRPC. (C) 2005 by American Society of Clinical Oncology.