Combined Gene and Radiation Therapy Induces Long-Term Prostate Cancer Remission

Results of a Phase II clinical trial indicated that an experimental gene therapy approach could successfully induce remission of prostate cancer when it was combined with directed radiation treatment.

Investigators at Houston Methodist Hospital (TX, USA) carried out the Phase II study on a group of 66 prostate cancer patients. The patient population was divided into two "arms": Arm A—low risk patients with cancer cells confined to the prostate, and Arm B—intermediate to high-risk patients with more aggressive prostate cancer.

The patients in Arm A were treated twice with intraprostatic injections of an adenoviral vector containing herpes simplex thymidine kinase (ADV/HSV-tk) followed by the antiviral drug valacyclovir. Patients in Arm B receive three injections of the adenoviral vector and valacyclovir. All patients were also treated with intensity-modulated radiotherapy (IMRT).

Results of the study, which followed the progress of the patients for a mean period of 100 months, were published in the December 12, 2015, online edition of the Journal of Radiation Oncology. They revealed that the 62 patients in both arms who completed the clinical trial had remarkably high five-year freedom from failure rates, meaning no indication by biochemical testing of cancer recurrence, of 94% and 91%, respectively. Prostate biopsies performed at 24 months after completion of treatment were negative in 83% of Arm A patients and 79% of Arm B patients. The majority of the patients in the clinical trial experienced few or no side effects or complications from the treatment regimen.

"We strategically used an adenovirus, similar to the one that causes the common cold, to carry the therapy agent—a herpes virus gene that produces the enzyme thymidine kinase or TK—directly into the tumor cells," said senior author Dr. E. Brian Butler, chairman of the department of radiation oncology at Houston Methodist Hospital. "Once the herpes virus gene was delivered and it started manufacturing TK, we gave patients a commonly used anti-herpes drug, valacyclovir. The combination attacked the herpes DNA, and the TK-producing tumor cells self-destructed, which is why the procedure is called "suicide gene therapy"."

Destruction of the tumor cells alerted the patients' immune systems to the presence of the cancer and triggered a massive immune response. "We have created a vaccine with the patient's own cancer cells, a treatment that complements, and may even enhance, what we can achieve with traditional radiation and hormonal therapies," said Dr. Butler.

A Phase III patient trial of the combination gene and radiation therapy, as required by the [US] Food and Drug Administration, is now underway.

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