Long-term outcome of phase I/II clinical trial of Ad-OC-TK/VAL gene therapy for hormone-refractory metastatic prostate cancer.
We evaluated the long-term safety and efficacy of Ad-OC-TK (recombinant adenoviral vector carrying an osteocalcin promoter-driven herpes simplex virus thymidine kinase gene) plus VAL (valacyclovir) gene therapy for hormone-refractory prostate cancer. Ad-OC-TK/VAL therapy is the first in vivo adenovirus-mediated gene therapy to be used to treat metastatic prostate cancer, including bone metastasis. Six patients were enrolled in this trial, and two doses of Ad-OC-TK (2.5 x 10(9) or 2.5 x 10(10) plaque-forming units) were injected into locally recurrent tumor or bone metastasis on day 1 and day 8. Patients were also given VAL (3 g/day) for 21 days. Safety and efficacy were evaluated for at least 8 months in each patient. All patients tolerated this therapy with no serious adverse events. One prostate-specific antigen (PSA) response (from 318.3 to 4.9 ng/ml) was observed with a time to PSA progression (TTP) of 12 months. Docetaxel (30 mg/m2 per week) and estramustine (560 mg/day) combination chemotherapy (DE) was given to three docetaxel-naive patients on PSA failure after gene therapy. All three patients had a PSA response to DE therapy with 21, 7, and 4 months of TTP. These results suggest that additional trials are warranted.
Shirakawa
Toshiro
T
International Center for Medical Research and Treatment, Kobe University School of Medicine, Kobe 650-0017, Japan. toshiro@med.kobe-u.ac.jp
Terao
Shuji
S
Hinata
Nobuyuki
N
Tanaka
Kazushi
K
Takenaka
Atsushi
A
Hara
Isao
I
Sugimura
Kazuro
K
Matsuo
Masafumi
M
Hamada
Katsuyuki
K
Fuji
Kohzo
K
Okegawa
Takatsugu
T
Higashihara
Eiji
E
Gardner
Thomas A
TA
Kao
Chinghai
C
Chung
Leland W K
LW
Kamidono
Sadao
S
Fujisawa
Masato
M
Gotoh
Akinobu
A
D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives; D000256:Adenoviridae / Q000235:genetics; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000008:administration & dosage; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary; D001842:Bone and Bones / Q000000981:diagnostic imaging; D000077143:Docetaxel; D015316:Genetic Therapy / Q000009:adverse effects; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000235:genetics*; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D011859:Radiography; D043823:Taxoids / Q000627:therapeutic use; D013937:Thymidine Kinase / Q000235:genetics*; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives
D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D043823:Taxoids; D015675:Osteocalcin; D000077143:Docetaxel; D013937:Thymidine Kinase; D017430:Prostate-Specific Antigen; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir