valacyclovir and Bone-Neoplasms

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.

Topics: Acyclovir; Adenoviridae; Aged; Androgen Antagonists; Antineoplastic Agents; Antiviral Agents; Bone and Bones; Bone Neoplasms; Docetaxel; Genetic Therapy; Genetic Vectors; Humans; Male; Middle Aged; Osteocalcin; Promoter Regions, Genetic; Prostate-Specific Antigen; Prostatic Neoplasms; Radiography; Taxoids; Thymidine Kinase; Valacyclovir; Valine

There is no effective therapy for hormone-refractory prostate cancer and a novel therapeutic modality, such as a gene therapy, should be actively pursued. Previously, Gardner and Chung conducted a phase I clinical trial of Ad-OC-TK (recombinant adenoviral vector containing osteocalcin promoter-driven herpes simplex virus thymidine kinase gene) plus VAL (valacyclovir) for the treatment of hormone-refractory prostate cancer at the University of Virginia. We report on our ongoing phase I/II clinical trial of Ad-OC-TK plus VAL for the treatment of advanced prostate cancer at the Kobe University Hospital, Japan.

Topics: Acyclovir; Adenoviridae; Aged; Antiviral Agents; Bone Neoplasms; Genetic Therapy; Hospitals, University; Humans; Japan; Male; Middle Aged; Osteocalcin; Prostatic Neoplasms; Thymidine Kinase; Valacyclovir; Valine