A randomized phase II trial of personalized peptide vaccine plus low dose estramustine phosphate (EMP) versus standard dose EMP in patients with castration resistant prostate cancer

Abstract

Personalized peptide vaccination (PPV) combined with chemotherapy could be a novel approach for many cancer patients. In this randomized study, we evaluated the anti-tumor effect and safety of PPV plus low-dose estramustine phosphate (EMP) as compared to standard-dose EMP for HLA-A2- or -A24-positive patients with castration resistant prostate cancer. Patients were randomized into groups receiving either PPV plus low-dose EMP (280 mg/day) or standard-dose EMP (560 mg/day). After disease progression, patients were switched to the opposite regime. The primary end point was progression-free survival (PFS). We randomly assigned 28 patients to receive PPV plus low-dose EMP and 29 patients to receive standard-dose EMP. Nineteen events in the PPV group and 20 events in the EMP group occurred during the first treatment. Median PFS for the first treatment was 8.5 months in the PPV group and 2.8 months in the EMP group with a hazard ratio (HR) of 0.28 (95% CI, 0.14-0.61; log-rank P = 0.0012), while there was no difference for median PFS for the second treatment. The HR for overall survival was 0.3 (95% CI, 0.1-0.91) in favor of the PPV plus low-dose EMP group (log-rank, P = 0.0328). The PPV plus low-dose EMP was well tolerated without major adverse effects and with increased levels of IgG and cytotoxic-T cell responses to the vaccinated peptides. PPV plus low-dose EMP was associated with an improvement in PSA-based PFS as compared to the standard-dose EMP alone.

Entering a New Era – Prostate Cancer Immuno-Therapy After the FDA Approval for Sipuleucel-T

“…As the peptides were injected s.c. vaccines were well tolerated and showed reactivity (DTH-reactions, CTL and IgG responses) and clinical activity (PSA declines up to 30 % in four out of 17 patients . In a second trial the combination with estramustine showed a better PFS as estramustine alone (p < 0.05) (Noguchi et al, 2010).…”

Personalized peptide vaccination in patients with refractory non-small cell lung cancer

“…We developed a new approach of peptide-based vaccination, named personalized peptide vaccination (PPV), in which vaccine antigens are selected and administered based on preexisting host immunity before vaccination (6)(7)(8)(9)(10)(11)(12)(13)(14). We have shown promising results of PPV in various types of advanced cancers (6)(7)(8)(9).…”

“…We have shown promising results of PPV in various types of advanced cancers (6)(7)(8)(9). For example, a recently conducted randomized clinical trial of PPV for patients with advanced prostate cancer suggested a potentially favorable clinical outcome in the vaccinated group (9). However, to improve clinical efficacy further, prognostic biomarkers that would make it possible to select patients for whom cancer vaccines would be appropriate remain to be identified.…”

Personalized peptide vaccination: A novel immunotherapeutic approach for advanced cancer

“…17 In the clinical trials of PPV conducted during the past several years, we have shown promising results in various types of cancers. 12,13,16,18,19 Table 1 shows the clinical responses in 500 advanced cancer patients who received PPV from October 2000 to October 2008. 16 The best clinical response assessed in 436 evaluable patients were partial response (PR) in 43 patients (10%), stable disease (SD) in 144 patients (33%) and progressive disease (PD) in 249 patients (57%), with a median overall survival of 9.9 mo.…”

“…16 The best clinical response assessed in 436 evaluable patients were partial response (PR) in 43 patients (10%), stable disease (SD) in 144 patients (33%) and progressive disease (PD) in 249 patients (57%), with a median overall survival of 9.9 mo. Of note, as shown in Figure 2, 18 In addition, PPV was also conducted in an early phase clinical trial of patients with Figure 2. Progression-free and overall survival in patients with castration-resistant prostate cancer using personalized peptide vaccination.…”