Phase I Clinical Trial of an Adenovirus/Prostate-Specific Antigen Vaccine for Prostate Cancer: Safety and Immunologic Results

• Published in: Clinical cancer research Vol. 15; no. 23; pp. 7375 - 7380
• Main Authors: LUBAROFF, David M, KONETY, Badrinath R, WILLIAMS, Richard D, LINK, Brian, GERSTBREIN, Jack, MADSEN, Tammy, SHANNON, Mary, HOWARD, Jeanne, PAISLEY, Jennifer, BOEGLIN, Diana, RATLIFF, Timothy L
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.12.2009
• Subjects: Adenoviridae - genetics; Aged; Aged, 80 and over; Antineoplastic agents; Biological and medical sciences; Cancer Vaccines - therapeutic use; Collagen - chemistry; Gelatin Sponge, Absorbable - chemistry; Gynecology. Andrology. Obstetrics; Hormones - metabolism; Humans; immunotherapy; Male; Male genital diseases; Medical sciences; Middle Aged; Neoplasm Metastasis; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; prostate cancer; Prostate-Specific Antigen - genetics; Prostatic Neoplasms - therapy; T-Lymphocytes - metabolism; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; vaccine; Human; Urinary system disease; Adenoviridae; Prostate disease; Toxicity; Tumoral marker; Vaccine; Malignant tumor; Virus; Prostate specific antigen; Treatment; Phase I trial; Safety; Gene therapy; Male genital diseases; Prostate cancer; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-09-1910

Purpose: We performed a phase I clinical trial of adenovirus/prostate-specific antigen (PSA) vaccine in men with measurable metastatic hormone-refractory disease. Experimental Design: Men with measurable metastatic disease received one vaccine injection. Toxicity, immune responses, changes in PSA doubling times, and patient survival were assessed. Thirty-two patients with hormone-refractory metastatic prostate cancer were treated with a single s.c. vaccine injection at one of three dose levels, either as an aqueous solution or suspended in a Gelfoam matrix. All patients returned for physical and clinical chemistry examinations at regular intervals up to 12 months after injections. Results: The vaccine was deemed safe at all doses in both administration forms. There were no serious vaccine-related adverse events; the most prevalent were localized erythema/ecchymoses and cold/flu-like symptoms. Anti-PSA antibodies were produced by 34% of patients and anti-PSA T-cell responses were produced by 68%. PSA doubling time was increased in 48%, whereas 55% survived longer than predicted by the Halabi nomogram. Conclusions: The adenovirus/PSA vaccine was proven safe with no serious vaccine-related adverse events. The majority of vaccinated patients produced anti-PSA T-cell responses and over half survived longer than predicted by nomogram. Although the latter data are only derived from a small number of patients in this phase I trial, they are encouraging enough to pursue further studies. (Clin Cancer Res 2009;15(23):7375–80)