title: Long-term outcome of phase I/II clinical trial of Ad-OC-TK/VAL gene therapy for hormone-refractory metastatic prostate cancer.
abstract: 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.
authors.affiliation: International Center for Medical Research and Treatment, Kobe University School of Medicine, Kobe 650-0017, Japan. toshiro@med.kobe-u.ac.jp
authors.forename: Toshiro
authors.initials: T
authors.lastname: Shirakawa
authors.forename: Shuji
authors.initials: S
authors.lastname: Terao
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hinata
authors.forename: Kazushi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takenaka
authors.forename: Isao
authors.initials: I
authors.lastname: Hara
authors.forename: Kazuro
authors.initials: K
authors.lastname: Sugimura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hamada
authors.forename: Kohzo
authors.initials: K
authors.lastname: Fuji
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Okegawa
authors.forename: Eiji
authors.initials: E
authors.lastname: Higashihara
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Gardner
authors.forename: Chinghai
authors.initials: C
authors.lastname: Kao
authors.forename: Leland W K
authors.initials: LW
authors.lastname: Chung
authors.forename: Sadao
authors.initials: S
authors.lastname: Kamidono
authors.forename: Masato
authors.initials: M
authors.lastname: Fujisawa
authors.forename: Akinobu
authors.initials: A
authors.lastname: Gotoh
mesh_terms: 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
chemical_list: 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