Garcia Jorge A, Klein Eric A, Magi-Galluzzi Cristina, Elson Paul, Triozzi Pierre, Dreicer Robert
Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio 44195, USA.
Clin Cancer Res. 2008 May 15;14(10):3052-9. doi: 10.1158/1078-0432.CCR-07-4731.
Granulocyte macrophage colony-stimulating factor (GM-CSF) and thalidomide are active agents in prostate cancer. This study assessed the biological effects and safety of GM-CSF and thalidomide in patients with localized prostate cancer before radical prostatectomy.
Locally advanced prostate cancer patients undergoing radical prostatectomy were recruited for this study. Treatment consisted of two 28-day cycles of GM-CSF (250 microg, s.c., thrice weekly) and thalidomide (200 mg, orally, daily) on days 1 to 28 of each cycle. Radical prostatectomy occurred within 7 to 10 days after completion of therapy. Pretreatment and posttreatment specimens were used to assess the expression of CD3, CD68, Ki-67, S100, PTEN, and CD31. Peripheral blood was examined for dendritic cells, regulatory T cells, and cytokines.
Twenty-eight patients were enrolled. No pathologic responses (P0) were observed and no unexpected toxicities or surgical complications occurred. Eighty-one percent of patients had a prostate-specific antigen decline (mean +/- SD decrease was 21.1 +/- 15.4%; median, 18.0%). With a median follow-up of 32 months, five patients have experienced progression. Radical prostatectomy tumor tissue specimens showed significant CD3 and S100 overexpression when compared with pretreatment biopsies. No significant changes in tumor macrophage infiltration were observed. Increased number of serum dendritic cell, as well as high serum levels of interleukin-8, basic fibroblast growth factor, and vascular endothelial growth factor, was also observed.
Neoadjuvant GM-CSF and thalidomide was safe and feasible and did not affect the perioperative morbidity of radical prostatectomy. Although no pathologic complete responses were observed, significant posttreatment tumor T-cell and dendritic cell infiltration was noted. No significant changes in serum cytokines, dendritic cells, or regulatory T cells were induced.
粒细胞巨噬细胞集落刺激因子（GM-CSF）和沙利度胺是前列腺癌的活性药物。本研究评估了GM-CSF和沙利度胺在根治性前列腺切除术前行局限性前列腺癌患者中的生物学效应和安全性。
招募接受根治性前列腺切除术的局部晚期前列腺癌患者参与本研究。治疗包括在每个周期的第1至28天进行两个28天周期的GM-CSF（250微克，皮下注射，每周三次）和沙利度胺（200毫克，口服，每日）。根治性前列腺切除术在治疗完成后7至10天内进行。治疗前和治疗后的标本用于评估CD3、CD68、Ki-67、S100、PTEN和CD31的表达。检测外周血中的树突状细胞、调节性T细胞和细胞因子。
28例患者入组。未观察到病理反应（P0），也未发生意外毒性或手术并发症。81%的患者前列腺特异性抗原下降（平均±标准差下降21.1±15.4%；中位数，18.0%）。中位随访32个月，5例患者病情进展。根治性前列腺切除术肿瘤组织标本与治疗前活检相比显示出显著的CD3和S100过表达。未观察到肿瘤巨噬细胞浸润的显著变化。还观察到血清树突状细胞数量增加，以及血清白细胞介素-8、碱性成纤维细胞生长因子和血管内皮生长因子水平升高。
新辅助GM-CSF和沙利度胺安全可行，不影响根治性前列腺切除术的围手术期发病率。虽然未观察到病理完全缓解，但注意到治疗后肿瘤T细胞和树突状细胞浸润显著。未诱导血清细胞因子、树突状细胞或调节性T细胞发生显著变化。
