Abstract
BackgroundCancer vaccine is one of the attractive treatment modalities for patients with castration-resistant prostate cancer (CRPC). However, because of delayed immune responses, its clinical benefits, besides for overall survival (OS), are not well captured by the World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Several surrogate markers for evaluation of cancer vaccine, including prostate-specific antigen doubling time (PSADT), are currently sought. The purpose of this study was to assess prospectively the PSA kinetics and immune responses, as well as the efficacy, safety, and biomarkers of personalized peptide vaccination (PPV) in progressive CRPC.MethodsOne hundred patients with progressive CRPC were treated with PPV using 2–4 positive peptides from 31 candidate peptides determined by both human leukocyte antigen (HLA) class IA types and the levels of immunoglobulin G (IgG) against each peptide. The association between immune responses and PSADT as well as overall survival (OS) was studied.ResultsPPV was safe and well tolerated in all patients with a median survival time of 18.8 months. Peptide-specific IgG and T-cell responses strongly correlated with PSADT (p < 0.0001 and p = 0.0007, respectively), which in turn showed correlation with OS (p = 0.018). Positive IgG responses and prolongation of PSADT during PPV were also significantly associated with OS (p = 0.001 and p = 0.004) by multivariate analysis.ConclusionsPSADT could be an appropriate surrogate marker for evaluation of the clinical benefit of cancer vaccine. Further randomized trials are needed to confirm these results.Trial registrationUMIN000001850
Highlights
Cancer vaccine is one of the attractive treatment modalities for patients with castration-resistant prostate cancer (CRPC)
We previously demonstrated that peptide vaccination (PPV) was safe and improved overall survival (OS) with immune responses in phase I, I/II, and II clinical trials in patients with CRPC [10,11,12,13,14,15,16]
Characteristics of the patients Between April 2009 and August 2011, 100 patients with CRPC were enrolled in this trial at Kurume University Hospital
Summary
Cancer vaccine is one of the attractive treatment modalities for patients with castration-resistant prostate cancer (CRPC). Changes in serum prostate-specific antigen (PSA) can reflect the burden of disease and clinical benefit in patients with castration-resistant prostate cancer (CRPC) with cytotoxic chemotherapy or hormonal agents known to kill tumor cells; these changes can have practical utility carried out with caution on the basis of the mechanism of action, and may depend on the time of sampling [9]. We previously demonstrated that PPV was safe and improved OS with immune responses in phase I, I/II, and II clinical trials in patients with CRPC [10,11,12,13,14,15,16] It was not addressed whether PSADT could be an appropriate surrogate marker for evaluation of the clinical benefit of cancer vaccine.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
