Results from a long-term clinical trial conducted by cancer researchers at Houston Methodist Hospital show that combining radiation treatment with "suicide gene therapy," a technique in which prostate cancer cells are genetically modified so they signal a patient's immune system to attack them, provides a safe and effective one-two punch against the disease.
The researchers compared two arms of patients and report high five-year overall survival rates of 97 percent and 94 percent, respectively. That's a five to 20 percent improvement for survival over historical studies. These findings are in the Dec. 12 online issue of the Journal of Radiation Oncology (JRO).
Sixty-six prostate cancer patients participated in the Phase II clinical trial between 1999 and 2003 and were split into two groups. One group with cancer cells confined to the prostate, designated Arm A, received only radiotherapy while the other with a more aggressive prostate cancer, Arm B, received both radiation and hormonal therapies.
Patients in Arm A received the experimental gene therapy twice during the study, while the Arm B group received the treatment three times.
"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 E. Brian Butler, M.D., chair of the Department of Radiation Oncology at Houston Methodist and senior author on the JRO paper.
"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.'"
Butler said that once the activated valacyclovir (trade name: Valtrex) starts destroying tumor cells, it also alerts the patient's immune system, previously unaware of the cancer's presence, that it is time to launch a massive attack.
"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 Butler, professor of radiation oncology, Weill Cornell Medicine.
According to the results reported in the JRO paper, the long-term outcome for prostate cancer patients receiving gene therapy in combination with radiotherapy with or without hormonal therapy is promising.
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 percent and 91 percent, respectively. Prostate biopsies performed at 24 months after completion of treatment were negative in 83 percent of Arm A patients and 79 percent of Arm B patients.
For all evaluative factors, the outcomes were remarkably higher than those achieved with radiotherapy alone (in data taken from historical studies used as controls).
"This is extremely pleasing to us, considering we had patients enrolled in our protocol after other physicians deemed them incurable," said Bin Teh, M.D., vice chair of Houston Methodist's Department of Radiation Oncology and lead author on the JRO paper. "We firmly believe this will be a viable treatment strategy."
Adding to the impressive therapeutic results, Teh said, is the fact that the majority of patients in the clinical trial experienced little or no side effects or complications. A Phase III patient trial, the final safety and efficacy evaluation for the in-situ immunomodulatory gene therapy before it can be approved by the Food and Drug Administration, is already underway. Prostate cancer is the most common cancer in men and causes significant mortality.
The researchers who collaborated with Butler and Teh on the Journal of Radiation Oncology paper were: Hiromichi Ishiyama, M.D., Ph.D., Kitasato University School of Medicine (Sagamilhara, Kanagawa, Japan); Wei-yuan Mai, M.D., Michael E. DeBakey VA Medical Center (Houston, Texas); and Timothy Thompson, Ph.D., The University of Texas MD Anderson Cancer Center (Houston, Texas).
The work was supported by grants from the National Cancer Institute, the Houston Methodist Hospital Foundation and the General Clinical Research Center.
To speak with E. Brian Butler, M.D., or Bin Teh, M.D., contact Gale Smith, Houston Methodist, at 281.627.0439 or email@example.com. For more information about Houston Methodist, visit houstonmethodist.org. Follow us on Twitter and Facebook or visit our blog.
B. Teh, H. Ishiyama, W-Y. Mai, T. Thompson, and E.B. Butler. Long-term Outcome of a Phase II Trial using Immunomodulatory In Situ Gene Therapy in Combination with Intensity-Modulated Radiotherapy with or without Hormonal Therapy in the Treatment of Prostate Cancer. Journal of Radiation Oncology; Published online Dec. 12, 2015 (DOI 10.1007/s13566-015-0239-y).
Gale Smith | EurekAlert!
More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
19.01.2018 | Materials Sciences
19.01.2018 | Health and Medicine
19.01.2018 | Physics and Astronomy