Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene therapy combined with IMRT found to reduce the rate of positive prostate biopsy after treatment for intermediate-risk prostate cancer patients

03.06.2014

Quality of life and toxicity measures also favorable

Combining oncolytic adenovirus-mediated cytotoxic gene therapy (OAMCGT) with intensity modulated radiation therapy (IMRT) reduces the risk of having a positive prostate biopsy two years after treatment in intermediate-risk prostate cancer without affecting patients’ quality of life, according to a study published in the June 1, 2014 edition of the International Journal of Radiation Oncology • Biology • Physics (Red Journal), the official scientific journal of the American Society for Radiation Oncology (ASTRO).


Previous prospective clinical trials in prostate cancer have shown that increasing the standard radiation dose of 70 Gy by 10 to 15 percent improves the biochemical disease-free survival in some prognostic risk groups; however, more than 25 percent of men with intermediate- or high-risk disease develop prostate-specific antigen (PSA) progression within 10 years, suggesting that radiation doses higher than 80 Gy may be necessary. This prospective randomized phase II trial examines the use of OAMCGT to improve the effectiveness of IMRT without increasing the radiation dose in intermediate-risk prostate cancer.

Based on encouraging results from a prior phase I trial, 44 patients were enrolled in this randomized phase II trial from January 2008 to July 2010. Patients were randomized to receive either OAMCGT with IMRT (21) or IMRT alone (23), and outcomes were focused on toxicity, quality of life and prostate biopsy findings at two years post-treatment. Eligible patients had newly diagnosed, clinically localized, intermediate-risk prostate cancer, defined as clinical stage T1/T2 with a Gleason score of 7 or a PSA of 10 to 20 ng/ml.

... more about:
»IMRT »Oncology »PSA »Radiation »biopsy »prostate »toxicity

Patients with a Gleason score of 5/6, a PSA <10 ng/ml and ≥50 percent positive biopsy cores were also eligible because it has been found that these patients tend to respond biochemically similar to patients with intermediate-risk disease. Of the 44 patients analyzed in this study, 82 percent (36) had stage T1 disease and 18 percent (8) had stage T2 disease. Sixteen percent (7) had a Gleason score of 6 and 84 percent (37) had a Gleason score of 7.

All patients were treated with IMRT (80 Gy in 2.0 Gy fractions over eight weeks). Patients who were treated with OAMCGT in addition to IMRT also received a single intraprostatic injection of 1 x 1012 viral particles of the Ad5-yCD/mutTKSR39rep-ADP adenovirus on the first day of treatment. Two days later, patients in the OAMCGT arm began IMRT treatment and received 5-FC (150 mg/kg/day, four times per day) and vGCV (1,800 mg/kg/day, twice daily) orally five days a week for two weeks.

Toxicity was assessed once a week during treatment. After completion of treatment, follow-up was conducted every three months for the first year post-treatment, at 18 and 24 months and then annually thereafter. Quality of life (QOL) was assessed at six, 12, 24 and 36 months post-treatment using the validated Expanded Prostate Cancer Index Composite (EPIC) and EuroQol EQ-5D instruments. A 12-core prostate biopsy was taken at 24 months post-treatment. Biopsies were examined by two pathologists blinded to the study treatments.

Gastrointestinal (GI) and genitourinary (GU) toxicity are the most common side effects of prostate radiation therapy. In this study, 5 percent of men (1) in the OAMCGT arm and 9 percent (2) in the IMRT alone arm experienced grade 2 or higher acute (≤90 days) GI toxicity. Grade 2 or higher acute GU toxicity was more prevalent in both arms, with 43 percent (9) in the OAMCGT arm and 31 percent (7) in the IMRT alone arm; however, there was no statistical significance in acute GI or GU toxicity between the two arms. Men in the OAMCGT arm experienced a higher occurrence of influenza-like symptoms, which were expected and attributed to the oncolytic adenovirus.

The sole significant difference in QOL in the EPIC domains (urinary incontinence, unitary irritation/obstruction, bowel, sexual, hormonal and overall satisfaction) at six months post-treatment was the sexual domain, which was better in the OAMCGT arm. The only significant difference in the EQ-5D domains (mobility, self-care, usual activities, pain and discomfort, anxiety and depression, and health state) was self-care at 24 months post-treatment, which was better in the OAMCGT arm.

An important outcome was prostate biopsy at two years post-treatment, which is prognostic of long-term results. In this study, 84 percent (37) of patients had two-year biopsies. For men in the OAMCGT arm, there was a 42 percent relative reduction in positive biopsy at two years, and a 60 percent relative reduction in men with <50 percent positive biopsy cores at baseline. At the time of this study’s findings, one patient in each arm had exhibited biochemical failure (4.8 percent in the OAMCGT arm and 4.3 percent in the IMRT alone arm). The events occurred 14.5 months post-treatment in the OAMCGT arm and 13.8 months post-treatment in the IMRT alone arm. No patients had developed hormone-refractory or metastatic disease, and no patients died from prostate cancer.

“The study’s results demonstrate that gene therapy generated few noticeable side effects and did not diminish the patient’s quality of life when combined with modern radiation therapy. Moreover, a greater percentage of men who received gene therapy and radiation had negative prostate biopsies two years after treatment relative to men who received radiation alone,” said Svend O. Freytag, PhD, lead author of the study and division head of biology research in the department of radiation oncology at Henry Ford Hospital in Detroit. “Our findings suggest that gene therapy has a potential role as a strategy to enhance outcomes, along with radiation therapy, while maintaining quality of life for our patients. This research helps open the door for further studies of this novel combination therapy approach in prostate cancer and other disease sites.”

Sites included in the multi-phase study are Henry Ford Hospital and Johns Hopkins School of Medicine in Baltimore.

For a copy of the study manuscript, contact Brittany Ashcroft at 703-839-7336. Learn more about the Red Journal.
 

Brittany Ashcroft | Eurek Alert!

Further reports about: IMRT Oncology PSA Radiation biopsy prostate toxicity

More articles from Health and Medicine:

nachricht Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University

nachricht The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>