Phase II study of personalized peptide vaccination for castration-resistant prostate cancer patients who failed in docetaxel-based chemotherapy

• Published in: The Prostate Vol. 72; no. 8; pp. 834 - 845
• Main Authors: Noguchi, Masanori, Moriya, Fukuko, Suekane, Shigetaka, Matsuoka, Kei, Arai, Gaku, Matsueda, Satoko, Sasada, Tetsuro, Yamada, Akira, Itoh, Kyogo
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.06.2012; Wiley-Liss
• Subjects: Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Biomarkers, Tumor - blood; Cancer Vaccines - therapeutic use; Cytokines - blood; Disease Progression; docetaxel; Humans; Immunity, Humoral; Immunotherapy; Interleukin-6 - blood; Kaplan-Meier Estimate; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Orchiectomy; overall survival; personalized peptide vaccine; Pharmacology. Drug treatments; Precision Medicine; Prospective Studies; prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - immunology; Prostatic Neoplasms - mortality; Taxoids - therapeutic use; Treatment Failure; Treatment Outcome; Tumors of the urinary system; Urinary tract. Prostate gland; Antineoplastic agent; Andrology; Nephrology; Prognosis; Prostate disease; Peptides; Cancerology; Castration; Taxane derivatives; Immunotherapy; Phase II trial; overall survival; Antimitotic; Male genital diseases; personalized peptide vaccine; Human; Treatment resistance; Urinary system disease; Gynecology; Docetaxel; Vaccine; Malignant tumor; Survival; Chemotherapy; Treatment; Prostate cancer; Cancer
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.21485

BACKGROUND Docetaxel‐based chemotherapy (DBC) showed limited clinical efficacy for castration‐resistant prostate cancer (CRPC) patients. To explore cancer vaccine as a new treatment modality, we conducted a phase II study of personalized peptide vaccine (PPV) for DBC‐resistant CRPC patients. METHODS Twenty DBC‐resistant CRPC patients and 22 patients with no prior DBC, as a control, were treated with PPV using peptides chosen from 31 peptides in patients, respectively. Cytokines, inflammatory markers, and immune responses were measured as candidate biomarkers. DBC‐resistant CRPC patients without PPV was set as a historical control for evaluation of clinical benefit of PPV. RESULTS Median overall survival (OS) time from the first vaccination was 14.8 months or not reached in DBC‐resistant CRPC patients and patients with no prior DBC (log‐rank; P = 0.07), respectively. Median OS time from the first day of progression disease was 17.8 and 10.5 months in DBC‐resistant CRPC patients receiving PPV and those with no PPV (P = 0.1656), respectively. Elevated IL‐6 levels before vaccination was an unfavorable factor for OS of DBC‐resistant CRPC patients (P = 0.0161, hazard ratio (HR): 0.024, 95% CI:0.001–0.499) as well as all 42 patients with PPV(P = 0.0011, HR: 0.212, 95% CI:0.068–0.661) by multivariable analysis. CONCLUSIONS Further clinical study of PPV is recommended for DBC‐resistant CRPC patients, because of the safety and possible prolongation of MST. Control of elevated IL‐6 by combined therapy may provide much better clinical outcome. Prostate 72:834–845, 2012. © 2011 Wiley Periodicals, Inc.