Effect of docetaxel chemotherapy on the activity of a gonadotropin releasing hormone vaccine in patients with advanced prostate cancer

BACKGROUND Gonadotropin releasing hormone (GnRH)‐DT vaccine elicits antibody that may inhibit prostate cancers indirectly by blocking GnRH induced gonadotropin release, and consequent androgen synthesis, and directly by immune effector and antiproliferative mechanisms. A pilot study was performed to...

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Bibliographic Details
Published in:	The Prostate Vol. 65; no. 4; pp. 316 - 321
Main Authors:	Triozzi, Pierre L., Bolger, Graeme B., Neidhart, Jeffrey, Rinehart, John J., Saleh, Mansoor, Allen, Karen O., Sellers, Sandra, Waddell, Mary J.
Format:	Journal Article
Language:	English
Published:	Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-12-2005 Wiley-Liss
Subjects:	Adenocarcinoma - blood Adenocarcinoma - drug therapy Adenocarcinoma - immunology Adenocarcinoma - therapy Aged Aged, 80 and over Anti-Inflammatory Agents, Non-Steroidal - therapeutic use antibody Antineoplastic Agents, Phytogenic - administration & dosage Antineoplastic Agents, Phytogenic - pharmacology Antineoplastic Agents, Phytogenic - therapeutic use Biological and medical sciences Cancer Vaccines - administration & dosage Cancer Vaccines - immunology Cohort Studies Combined Modality Therapy dexamethasone Dexamethasone - therapeutic use Diphtheria-Tetanus Vaccine - administration & dosage Diphtheria-Tetanus Vaccine - immunology Gonadotropin-Releasing Hormone - immunology Gynecology. Andrology. Obstetrics Humans immunotherapy Luteinizing Hormone - blood Male Male genital diseases Medical sciences Middle Aged Nephrology. Urinary tract diseases Pilot Projects Prostate-Specific Antigen - blood Prostatic Neoplasms - blood Prostatic Neoplasms - drug therapy Prostatic Neoplasms - immunology Prostatic Neoplasms - therapy Taxoids - administration & dosage Testosterone - blood Tumors Tumors of the urinary system Urinary tract. Prostate gland Antineoplastic agent Andrology Nephrology Prostate disease Prevention Taxane derivatives Immunotherapy Advanced stage Antimitotic Male genital diseases Human Corticosteroid Urinary system disease Dexamethasone Steroid hormone Antibody Gynecology Antiinflammatory agent Docetaxel Vaccine Malignant tumor Gonadotropin Biological activity Immunoprophylaxis Chemotherapy Treatment Prostate cancer
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Summary:	BACKGROUND Gonadotropin releasing hormone (GnRH)‐DT vaccine elicits antibody that may inhibit prostate cancers indirectly by blocking GnRH induced gonadotropin release, and consequent androgen synthesis, and directly by immune effector and antiproliferative mechanisms. A pilot study was performed to determine how to best combine GnRH‐DT vaccine with potentially immunosuppressive chemotherapy. METHODS Patients with metastatic, hormone‐refractory prostate cancer were randomized into either a concurrent cohort, in which they received docetaxel on day 1 of weeks 1, 4, 7, and 10 and GnRH‐DT vaccine on day 2 of weeks 1, 3, and 7 or a sequential cohort, in which they received GnRH‐DT vaccine on weeks 1, 3, and 7 before beginning docetaxel on week 10. GnRH‐DT vaccine was administered intramuscularly. Docetaxel was infused intravenously after pre‐medication with high‐dose dexamethasone, and infusions repeated every 3 weeks in the absence of toxicity or progressive cancer. RESULTS GnRH‐DT vaccine and docetaxel were well tolerated without evidence of significant local or systemic toxicities. Anti‐GnRH antibody was elicited in six of six treated concurrently and five of six treated sequentially. The kinetics of antibody induction and the titers of antibody achieved in both treatment cohorts were similar. Anti‐GnRH antibody persisted for up to 28 weeks in a patient maintained on docetaxel. CONCLUSION The administration of docetaxel with high‐dose dexamethasone does not inhibit the ability of patients with advanced prostate cancer to be immunized with GnRH‐DT vaccine. Prostate. © 2005 Wiley‐Liss, Inc.
Bibliography:	istex:0D66503BFA3A20A6A19CA3B3DECF53C6AFFEBE81 Aphton Corporation, Philadelphia, Pennsylavania University of Alabama Comprehensive Cancer Center Core - No. 5P30CA13148 ark:/67375/WNG-WV6B7NWG-T ArticleID:PROS20295
ISSN:	0270-4137 1097-0045
DOI:	10.1002/pros.20295