Evaluation of phase I/II clinical trials in prostate cancer with dendritic cells and PSMA peptides.
BACKGROUND
A phase I trial involving patients with advanced prostate cancer was conducted to assess the safe administration of dendritic cells (DC) and HLA-A0201-specific prostate-specific membrane antigen (PSMA) peptides (PSM-P1 or -P2). Thirty-three of the phase I participants were subsequently enrolled in a phase II trial, which involved six infusions of DC pulsed with PSM-P1 and -P2 peptides.


METHODS
Clinical monitoring was conducted up to 770 days from the start of the phase I study. Data collected included: complete blood count, bone and total alkaline phosphatase, prostate markers, physical examination, performance status, bone scan, ProstaScint scan, and chest X-ray, as well as assays to monitor cellular immune responses.


RESULTS
Nine partial responders were identified in the phase II study based on National Prostate Cancer Project (NPCP) criteria, plus 50% reduction of prostate-specific antigen. Four of the partial responders were also responders in the phase I study, with an average response duration of 225 days. Their combined average total response period was over 370 days. Five other responders were nonresponders in the phase I study. Their average partial response period was 196 days.


CONCLUSIONS
The responses observed in the phase I and II clinical trials were significant and of long duration. The partial-responder group included patients who continued to respond from phase I, as well as those who started to respond during the phase II trial.
Tjoa
B A
BA
Cancer Research Division, Pacific Northwest Cancer Foundation, Northwest Hospital, Seattle, Washington 98125, USA.
Simmons
S J
SJ
Bowes
V A
VA
Ragde
H
H
Rogers
M
M
Elgamal
A
A
Kenny
G M
GM
Cobb
O E
OE
Ireton
R C
RC
Troychak
M J
MJ
Salgaller
M L
ML
Boynton
A L
AL
Murphy
G P
GP
D000469:Alkaline Phosphatase / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000627:therapeutic use*; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D002268:Carboxypeptidases / Q000627:therapeutic use*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000637:transplantation*; D005069:Evaluation Studies as Topic; D043425:Glutamate Carboxypeptidase II; D006801:Humans; D008297:Male; D008991:Monitoring, Physiologic; D011471:Prostatic Neoplasms / Q000628:therapy*; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D000469:Alkaline Phosphatase; D002268:Carboxypeptidases; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II