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Clinical and Biological Effects of Neoadjuvant Sargramostim and Thalidomide in Patients with Locally Advanced Prostate Carcinoma

Authors' Affiliations: Departments of ¹ Solid Tumor Oncology, ² Anatomic Pathology, ³ Biostatistics, and ⁴ Urology, Cleveland Clinic Taussig Cancer Institute and Glickman Urological and Kidney Institute, Cleveland, Ohio

Requests for reprints: Jorge A. Garcia, Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Avenue/R35, Cleveland, OH 44195. Phone: 216-444-7774; Fax: 216-444-9464; E-mail: Garciaj4{at}ccf.org.

Purpose: 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.

Experimental Design: Locally advanced prostate cancer patients undergoing radical prostatectomy were recruited for this study. Treatment consisted of two 28-day cycles of GM-CSF (250 µg, 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.

Results: 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.

Conclusions: 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.