BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that stimulates dendritic cells (DCs) and promotes uptake of tumor antigens by DCs leading to T-cell cross-priming.
Lenalidomide (Revlimid) is an immunomodulatory analog of thalidomide with significant T-cell stimulatory and antiangiogenic properties. GM-CSF in combination with thalidomide induces prostate-specific antigen (PSA) responses in 20% to 25% of patients with castration-resistant prostate cancer (CRPC). In an effort to further evaluate the clinical and immune activity of GM-CSF and lenalidomide, we conducted a phase I-II trial in patients with CRPC.
METHODS: Asymptomatic patients with CRPC were enrolled. Prior immunotherapy or chemotherapy was not allowed. All the patients received 250μg of GM-CSF administered subcutaneously 3 times weekly along with 25mg/d of lenalidomide administered orally on days 1 to 21 of a 28-day cycle. The primary end points were objective, PSA response, and safety. Exploratory end points included activation of circulating DCs, regulatory T cells, and Th1 cytokine production.
RESULTS: Thirty-two patients were enrolled in the study. No dose-limiting toxicities occurred in the phase I portion of the study. Although 81% of the patients achieved a decline in the levels of PSA while on therapy, only 4 achieved a PSA level decline of ≥50%. The overall response rate among 11 patients with response evaluation criteria in solid tumors-defined measurable disease was 18%. Overall toxicity was G1 and G2 in nature and included fatigue observed in 69% of the patients, nausea/vomiting in 34%, and diarrhea in 28% of the patients. Grade 3 or 4 toxicities occurred in 22% of the patients and were primarily thrombocytopenia (9%) or neutropenia (19%) or both.
CONCLUSIONS: Administration of GM-CSF and lenalidomide in patients with CRPC is safe with modest evidence of antitumor activity and no immune changes observed.
Written by:
Garcia JA, Elson P, Tyler A, Triozzi P, Dreicer R. Are you the author?
Department of Solid Tumor Oncology, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH; Department of Biostatistics, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH.
Reference: Urol Oncol. 2013 Mar 16. pii: S1078-1439(12)00467-X.
doi: 10.1016/j.urolonc.2012.12.004
PubMed Abstract
PMID: 23510862
