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.
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.
Department of Urology, Kurume University School of Medicine, Kurume, Japan. noguchi@med.kurume-u.ac.jp
Masanori
M
Noguchi
Tatsuyuki
T
Kakuma
Hirotsugu
H
Uemura
Yasutomo
Y
Nasu
Hiromi
H
Kumon
Yasuhiko
Y
Hirao
Fukuko
F
Moriya
Shigetaka
S
Suekane
Kei
K
Matsuoka
Nobukazu
N
Komatsu
Shigeki
S
Shichijo
Akira
A
Yamada
Kyogo
K
Itoh
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004961:Estramustine / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009919:Orchiectomy; D010455:Peptides / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery; D012871:Skin Diseases / Q000139:chemically induced; D016019:Survival Analysis; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
D019496:Cancer Vaccines; D010455:Peptides; D004961:Estramustine