A randomized controlled trial comparing personalized peptide vaccine plus low-dose estramustine with full dose estramustine for patients with hormone refractory prostate cancer

INTERVENTION: A: Select peptide candidates (up to 4), to which CTL precursors or peptide‐specific IgGs are detected before vaccination, and administer peptides (maximum 4) that showed the highest reactivity. Emulate these peptides individually and subcutaneously inject them separately (3.0 mg/1.5‐3.0 ml/peptide) every 2 weeks interval. Start internal use of estramustine 2 cap (2X) (280 mg/day) on the same day with peptide vaccination. After PD(Three consecutive and 125% increase from baseline PSA levels at least two weeks apart), patients are treated with B regime. B: Full dose of estramustine alone (4 cap 2X, 560 mg/day) After PD(Three consecutive and 125% increase from baseline PSA levels at least two weeks apart), patients are treated with A regime. CONDITION: Prostate cancer PRIMARY OUTCOME: Progression‐free survival SECONDARY OUTCOME: 1. adverse events; 2. overall survival; 3. Subjective effects (pain due to metastatic lesion, symptoms based on urinary disturbance due to primary lesion, PS, progression of cancer / change of body weight according to improvement) and evaluation of quality of life based on FACT examination sheet.; 4. Evaluation of immunological responses (cytotoxic T lymphocytes (CTL), CTL precursors, anti‐peptide IgG) before and after peptide vaccination. INCLUSION CRITERIA: The subjects must satisfy the following conditions. 1)Patients must be diagnosed as prostate cancer pathologically after the treatment of castration, LH‐RH analogue therapy, anti‐andorogen therapy, or female hormone therapy. The patients must be suffering from hormone refractory prostate cancer(#1,2,3,4) #1: The measurable tumor size must be more than 2 cm by X‐ray and the level of PSA must increase more than 3 times consecutively at more than 2 weeks interval. #2: Patients must be drug‐free more than 4 weeks after hormone therapies or chemotherapies. The hormone withdrawal syndrome must be ruled out. #3: In the cases of patients without castration, the LH‐RH analogue therapy will be continued to keep the level of testosterone. #4: Patients must not receive the treatment with bisphosphonate and steroid. 2) Patients must be positive for HLA‐A2 or HLA‐A24. 3) Patients must have IgG reactive to at least one of peptide candidates. 4) When p