A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer.
OBJECTIVE
Docetaxel has activity against androgen-independent prostate cancer and preclinical studies have shown that taxane-based chemotherapy can enhance antitumor response of vaccines. The primary objective of this study was to determine if concurrent docetaxel (with dexamethasone) had any effect on generating an immune response to the vaccine. Secondary end points were whether vaccine could be given safely with docetaxel and the clinical outcome of the treatment regimen.


METHODS
The vaccination regimen was composed of (a) recombinant vaccinia virus (rV) that expresses the prostate-specific antigen gene (rV-PSA) admixed with (b) rV that expresses the B7.1 costimulatory gene (rV-B7.1), and (c) sequential booster vaccinations with recombinant fowlpox virus (rF-) containing the PSA gene (rF-PSA). Patients received granulocyte macrophage colony-stimulating factor with each vaccination. Twenty-eight patients with metastatic androgen-independent prostate cancer were randomized to receive either vaccine and weekly docetaxel or vaccine alone. Patients on the vaccine alone arm were allowed to cross over to receive docetaxel alone at time of disease progression. The ELISPOT assay was used to monitor immune responses for PSA-specific T cells.


RESULTS
The median increase in these T-cell precursors to PSA was 3.33-fold in both arms following 3 months of therapy. In addition, immune responses to other prostate cancer-associated tumor antigens were also detected postvaccination. Eleven patients who progressed on vaccine alone crossed over to receive docetaxel at time of progression. Median progression-free survival on docetaxel was 6.1 months after receiving vaccine compared with 3.7 months with the same regimen in a historical control.


CONCLUSIONS
This is the first clinical trial to show that docetaxel can be administered safely with immunotherapy without inhibiting vaccine specific T-cell responses. Furthermore, patients previously vaccinated with an anticancer vaccine may respond longer to docetaxel compared with a historical control of patients receiving docetaxel alone. Larger prospective clinical studies will be required to validate these findings.
Arlen
Philip M
PM
Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892-1750, USA.
Gulley
James L
JL
Parker
Catherine
C
Skarupa
Lisa
L
Pazdur
Mary
M
Panicali
Dennis
D
Beetham
Patricia
P
Tsang
Kwong Y
KY
Grosenbach
Douglas W
DW
Feldman
Jarett
J
Steinberg
Seth M
SM
Jones
Elizabeth
E
Chen
Clara
C
Marte
Jennifer
J
Schlom
Jeffrey
J
Dahut
William
W
D000135:Acid Phosphatase / Q000097:blood; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000502:physiology; D000941:Antigens / Q000097:blood; D000951:Antigens, Neoplasm; D000954:Antigens, Surface / Q000097:blood; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018592:Cross-Over Studies; D018572:Disease-Free Survival; D000077143:Docetaxel; D043425:Glutamate Carboxypeptidase II / Q000097:blood; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018396:Mucin-1; D009077:Mucins / Q000097:blood; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D043823:Taxoids / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods
D000728:Androgens; D000941:Antigens; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D000972:Antineoplastic Agents, Phytogenic; D019496:Cancer Vaccines; D006023:Glycoproteins; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins; D043823:Taxoids; D000077143:Docetaxel; D000135:Acid Phosphatase; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen