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 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.


CONCLUSIONS
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.
Triozzi
Pierre L
PL
Comprehensive Cancer Center, The University of Alabama at Birmingham, Birmingham, Alabama 35294-3300, USA. pierre.triozzi@ccc.uab.edu
Bolger
Graeme B
GB
Neidhart
Jeffrey
J
Rinehart
John J
JJ
Saleh
Mansoor
M
Allen
Karen O
KO
Sellers
Sandra
S
Waddell
Mary J
MJ
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000627:therapeutic use; D022422:Diphtheria-Tetanus Vaccine / Q000008:administration & dosage* / Q000276:immunology; D000077143:Docetaxel; D007987:Gonadotropin-Releasing Hormone / Q000276:immunology*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D043823:Taxoids / Q000008:administration & dosage*; D013739:Testosterone / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000972:Antineoplastic Agents, Phytogenic; D019496:Cancer Vaccines; D022422:Diphtheria-Tetanus Vaccine; D043823:Taxoids; D000077143:Docetaxel; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D003907:Dexamethasone; D007986:Luteinizing Hormone; D017430:Prostate-Specific Antigen