Phase II Trial of Sipuleucel-T and Stereotactic Ablative Body Radiation for Patients with Metastatic Castrate-Resistant Prostate Cancer.
Raquibul HannanMichael J DohopolskiLaurentiu M PopSamantha MannalaLori WatumullDana MathewsAng GaoAurelie GarantYull E ArriagaIsaac BowmanJin-Sung ChungJing WangKiyoshi AriizumiChul AhnRobert TimmermanKevin CourtneyPublished in: Biomedicines (2022)
(1) We hypothesized that adding concurrent stereotactic ablative radiotherapy (SAbR) would increase the time to progression in patients with metastatic castrate-resistant prostate cancer (mCRPCA) treated with sipuleucel-T. (2) Patients with a history of prostate cancer (PC), radiographic evidence of metastatic disease, and rising prostate-specific antigen (PSA) > 0.2 ng/dL on castrate testosterone levels were enrolled in this single-arm phase II clinical trial and treated with sipuleucel-T and SAbR. The primary endpoint was time to progression (TTP). Cellular and humoral responses were measured using ELISpot and Luminex multiplex assays, respectively. (3) Twenty patients with mCRPC were enrolled and treated with SAbR to 1-3 sites. Treatment was well tolerated with 51, 8, and 4 treatment-related grade 1, 2, and 3 toxicities, respectively, and no grade 4 or 5 adverse events. At a median follow-up of 15.5 months, the median TTP was 11.2 weeks (95% CI; 6.8-14.0 weeks). Median OS was 76.8 weeks (95% CI; 41.6-130.8 weeks). This regimen induced both humoral and cellular immune responses. Baseline M-MDSC levels were elevated in mCRPC patients compared to healthy donors ( p = 0.004) and a decline in M-MDSC was associated with biochemical response ( p = 0.044). Responders had lower baseline uric acid levels ( p = 0.05). No clear correlation with radiographic response was observed. (4) While the regimen was safe, the PC-antigen-specific immune response induced by SAbR did not yield a synergistic clinical benefit for patients treated with sipuleucel-T compared to the historically reported outcomes.
Keyphrases
- prostate cancer
- immune response
- clinical trial
- phase ii
- radical prostatectomy
- uric acid
- newly diagnosed
- open label
- gestational age
- end stage renal disease
- metabolic syndrome
- toll like receptor
- dendritic cells
- squamous cell carcinoma
- chronic kidney disease
- replacement therapy
- early stage
- small cell lung cancer
- high throughput
- radiation therapy
- radiation induced
- combination therapy
- diabetic rats
- study protocol
- drug delivery
- adipose tissue
- phase iii
- patient reported outcomes
- type diabetes
- randomized controlled trial
- drug induced
- smoking cessation
- cancer therapy
- stress induced