Long-term outcome of phase I/II clinical trial of Ad-OC-TK/VAL gene therapy for hormone-refractory metastatic prostate cancer

Toshiro Shirakawa, Shuji Terao, Nobuyuki Hinata, Kazushi Tanaka, Atsushi Takenaka, Isao Hara, Kazuro Sugimura, Masafumi Matsuo, Katsuyuki Hamada, Kohzo Fuji, Takatsugu Okegawa, Eiji Higashihara, Thomas Gardner, Chinghai Kao, Leland W K Chung, Sadao Kamidono, Masato Fujisawa, Akinobu Gotoh

Research output: Contribution to journalArticle

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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 × 109 or 2.5 × 1010 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/m 2 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.

Original languageEnglish
Pages (from-to)1225-1232
Number of pages8
JournalHuman Gene Therapy
Volume18
Issue number12
DOIs
StatePublished - Dec 1 2007

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valacyclovir
Phase II Clinical Trials
Clinical Trials, Phase I
Genetic Therapy
Prostatic Neoplasms
docetaxel
Hormones
Prostate-Specific Antigen
Estramustine
Neoplasm Metastasis
Safety
Bone Neoplasms
Thymidine Kinase
Osteocalcin
Simplexvirus
Combination Drug Therapy
Adenoviridae
Therapeutics

ASJC Scopus subject areas

  • Genetics

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Long-term outcome of phase I/II clinical trial of Ad-OC-TK/VAL gene therapy for hormone-refractory metastatic prostate cancer. / Shirakawa, Toshiro; Terao, Shuji; Hinata, Nobuyuki; Tanaka, Kazushi; Takenaka, Atsushi; Hara, Isao; Sugimura, Kazuro; Matsuo, Masafumi; Hamada, Katsuyuki; Fuji, Kohzo; Okegawa, Takatsugu; Higashihara, Eiji; Gardner, Thomas; Kao, Chinghai; Chung, Leland W K; Kamidono, Sadao; Fujisawa, Masato; Gotoh, Akinobu.

In: Human Gene Therapy, Vol. 18, No. 12, 01.12.2007, p. 1225-1232.

Research output: Contribution to journalArticle

Shirakawa, T, Terao, S, Hinata, N, Tanaka, K, Takenaka, A, Hara, I, Sugimura, K, Matsuo, M, Hamada, K, Fuji, K, Okegawa, T, Higashihara, E, Gardner, T, Kao, C, Chung, LWK, Kamidono, S, Fujisawa, M & Gotoh, A 2007, 'Long-term outcome of phase I/II clinical trial of Ad-OC-TK/VAL gene therapy for hormone-refractory metastatic prostate cancer', Human Gene Therapy, vol. 18, no. 12, pp. 1225-1232. https://doi.org/10.1089/hum.2007.074
Shirakawa, Toshiro ; Terao, Shuji ; Hinata, Nobuyuki ; Tanaka, Kazushi ; Takenaka, Atsushi ; Hara, Isao ; Sugimura, Kazuro ; Matsuo, Masafumi ; Hamada, Katsuyuki ; Fuji, Kohzo ; Okegawa, Takatsugu ; Higashihara, Eiji ; Gardner, Thomas ; Kao, Chinghai ; Chung, Leland W K ; Kamidono, Sadao ; Fujisawa, Masato ; Gotoh, Akinobu. / Long-term outcome of phase I/II clinical trial of Ad-OC-TK/VAL gene therapy for hormone-refractory metastatic prostate cancer. In: Human Gene Therapy. 2007 ; Vol. 18, No. 12. pp. 1225-1232.
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