Amato Robert J, Hernandez-McClain Joan, Henary Haby
Genitourinary Oncology Program, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
Urol Oncol. 2009 Jan-Feb;27(1):8-13. doi: 10.1016/j.urolonc.2007.10.014. Epub 2008 Jan 14.
To assess the efficacy of granulocyte macrophage colony-stimulating factor (GM-CSF) in combination with thalidomide on prostate-specific antigen (PSA) reduction in hormone-naïve prostate carcinoma (HNPC) patients with rising PSA levels after definitive local treatment.
HNPC patients (n = 21) with evidence of progression demonstrated by 3 consecutive rises in PSA and no evidence of radiographic involvement were treated on a chronic dosing schedule with GM-CSF. Patients received 250 microg/m2 (maximum 500 microg) 3 times a wk by subcutaneous injection, with injections at least 24 h apart. Thalidomide administration began concurrently with an initial dose of 100 mg daily for 7 consecutive days. During wk 2 to 4, the dose was escalated every 7 d by 100 mg per individual tolerance to a maximum of 400 mg. The maximum tolerated dose of thalidomide was continued without interruption. PSA, testosterone, and routine laboratory parameters were measured every 6 wk.
One patient was not evaluable because of noncompliance. For the 20 evaluable patients, baseline PSA levels ranged from 1.3 to 61.0 ng/ml. Nineteen patients left the study at 3.0 to 33.3 mo, secondary to individual tolerance, progressive disease, or development of a second primary tumor. One patient continues to receive therapy at 33.8 mo. Two patients did not respond to the therapy. For the 18 patients who did respond, the median reduction in PSA level was 59% (range 26%-89%), and the median duration of response was 11 mo (range 4.5-36). Grades 1-2 toxicity included peripheral neuropathy, fatigue, skin rash, and constipation. One patient had deep-vein thrombosis/pulmonary embolism.
GM-CSF plus thalidomide can be administered successfully with encouraging antitumor activity and reversible toxicity. This may represent an alternative to hormonal therapy.
评估粒细胞巨噬细胞集落刺激因子（GM-CSF）联合沙利度胺对初始接受局部治疗后前列腺特异性抗原（PSA）水平升高的激素初治前列腺癌（HNPC）患者降低PSA的疗效。
21例HNPC患者，PSA连续3次升高证明有疾病进展且无影像学受累证据，按慢性给药方案接受GM-CSF治疗。患者皮下注射GM-CSF，剂量为250μg/m²（最大500μg），每周3次，每次注射间隔至少24小时。沙利度胺与初始剂量100mg/日同时开始给药，连续7天。在第2至4周期间，根据个体耐受性每7天剂量递增100mg，最大剂量为400mg。持续给予沙利度胺最大耐受剂量，不间断。每6周测量PSA、睾酮和常规实验室参数。
1例患者因未遵守治疗方案无法评估。对于20例可评估患者，基线PSA水平为1.3至61.0ng/ml。19例患者在3.0至33.3个月时因个体耐受性、疾病进展或发生第二原发性肿瘤而退出研究。1例患者在33.8个月时继续接受治疗。2例患者对治疗无反应。对于18例有反应的患者，PSA水平的中位降低率为59%（范围26%-89%），中位反应持续时间为11个月（范围4.5-36个月）。1-2级毒性包括周围神经病变、疲劳、皮疹和便秘。1例患者发生深静脉血栓形成/肺栓塞。
GM-CSF联合沙利度胺可成功给药，具有令人鼓舞的抗肿瘤活性和可逆毒性。这可能是激素治疗的一种替代方法。
