New immunotherapeutic paradigms for castration-resistant prostate cancer

Trial Watch—Immunostimulation with cytokines in cancer therapy

“…114 The safety and efficacy of G-CSF have been assessed in 11 breast carcinoma patients, who were treated with subcutaneous G-CSF in combination with 5-fluorouracil (5-FU), epirubicin, cyclophosphamide and paclitaxel (NCT02225652). 98 The clinical profile of GM-CSF has been investigated in (1) 58 patients with newly diagnosed, treatment-naive CML, who received subcutaneous GM-CSF in combination with IFN-a, 101 (2) two cohorts of 125 and 11 subjects with castration-resistant prostate carcinoma, who were treated with GM-CSF s.c. as a maintenance therapy upon successful docetaxel-and prednisone-based chemotherapy, 115 or in combination with thalidomide, 116,117 respectively; 103,111 (3) 32 individuals with metastatic melanoma, receiving subcutaneous GM-CSF along with the FDA-approved, cytotoxic T lymphocyte-associated protein 4 (CTLA4)-blocking monoclonal antibody (mAb) ipilimumab; 109 and (4) 41 patients affected with advanced solid neoplasms, who were treated with GM-CSF s.c. in combination with local radiotherapy, [118][119][120] with the specific aim to provoke systemic tumor-targeting immune responses (NCT02474186). 110 Taken together, the results of these studies confirm that the subcutaneous administration of GM-CSF to cancer patients is safe and may boost the therapeutic activity of other treatments, at least in a proportion of individuals.…”

Trial watch: Naked and vectored DNA-based anticancer vaccines

“…NCT01145508 (a Phase II study) is investigating the therapeutic profile of a vaccination strategy based on the sequential, subcutaneous administration of PROSTVAC Ò -V/TRICOM and PROSTVAC Ò -F/TRICOM, alone of combined with conventional chemotherapy, to subjects with metastatic, castration-resistant prostate carcinoma. [193][194][195] So far, 10 individuals have been enrolled in the study, 8 of which effectively started treatment with either chemotherapy only (2 patients) or chemotherapy plus vaccination (6 patients). Only 3 patients completed the entire course of therapy (1 from the chemotherapy arm, 2 from the chemotherapy plus vaccination arm), owing to adverse effects, death or physician's decision.…”

Trial Watch

“…, a fusion between a biologically active peptide and the constant fragment of a mAb) that blocks angiopoietin 1 and 2; 80 - 82 and rilotumumab (a human IgG2 also known as AMG 102), which binds to—hence neutralizing—hepatocyte growth factor (HGF) 83 - 85 . During the last 13 mo, carlumab and trebananib have been employed for dose-escalation studies in patients affected by advanced solid tumors, 86 - 88 while rilotumumab has been tested in combination with mitoxantrone (an anthracycline that induces the immunogenic demise of cancer cells) 8 , 89 , 90 and prednisone in patients with progressive, taxane-refractory castration-resistant prostate cancer 91 , 92 . All these agents were well tolerated, yet only trebananib was associated with durable antitumor activity in a fraction of patients 87 …”