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. 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 10^12 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."
See the original post here:
Gene therapy combined with IMRT reduces rate of positive prostate biopsy after treatment for intermediate-risk ...
- Gene Therapy: Ethical Issues: Information from Answers.com - February 6th, 2014 [February 6th, 2014]
- Gene, immune therapy help cancer war - April 10th, 2014 [April 10th, 2014]
- Gene Therapy - Genetics Home Reference - Your guide to ... - April 10th, 2014 [April 10th, 2014]
- What is gene therapy? - Genetics Home Reference - April 10th, 2014 [April 10th, 2014]
- Gene therapy - Wikipedia, the free encyclopedia - April 10th, 2014 [April 10th, 2014]
- Gene Therapy PSA Dan Lesser Period 2 - Video - April 15th, 2014 [April 15th, 2014]
- Gene therapy basics - Video - April 15th, 2014 [April 15th, 2014]
- In vivo gene therapy - Video - April 15th, 2014 [April 15th, 2014]
- Ex vivo gene therapy - Video - April 15th, 2014 [April 15th, 2014]
- Broad Institute Gets Patent on Revolutionary Gene-Editing Method - April 17th, 2014 [April 17th, 2014]
- Gene Therapy - Video - April 17th, 2014 [April 17th, 2014]
- Mark Hamalainen: Gene Therapy - Video - April 17th, 2014 [April 17th, 2014]
- JFK - Gene Therapy for Brain Tumors - Video - April 18th, 2014 [April 18th, 2014]
- Fixing the Liver with New Gene Therapy (Brainstorm Ep178) - Video - April 18th, 2014 [April 18th, 2014]
- Gene Therapy | Buzzle.com - April 22nd, 2014 [April 22nd, 2014]
- Gene Therapy I - RCN Corporation - April 22nd, 2014 [April 22nd, 2014]
- Ricky Ashby Microbiology Podcast - Video - April 22nd, 2014 [April 22nd, 2014]
- Regrown nerves boost bionic ears - April 24th, 2014 [April 24th, 2014]
- Cochlear Implant Plus Gene Therapy Could Restore Hearing to the Deaf - April 24th, 2014 [April 24th, 2014]
- Scientists reverse memory loss in mice with Alzheimer's - April 24th, 2014 [April 24th, 2014]
- Bionic Ears Boosted by Gene Therapy and Regrown Nerves - April 24th, 2014 [April 24th, 2014]
- Study: Gene Therapy May Boost Cochlear Implants - April 24th, 2014 [April 24th, 2014]
- Gene therapy may boost hearing, study finds - April 24th, 2014 [April 24th, 2014]
- Pronounce Medical Words Gene Therapy - Video - April 24th, 2014 [April 24th, 2014]
- Gene therapy may boost power of cochlear implants, study says - April 25th, 2014 [April 25th, 2014]
- Gene therapy shows promise to help people regrow auditory nerve cells - April 25th, 2014 [April 25th, 2014]
- Cochlear Implant Also Uses Gene Therapy to Improve Hearing - April 25th, 2014 [April 25th, 2014]
- Gene Therapy May Enhance Cochlear Implants, Animal Study Finds - April 25th, 2014 [April 25th, 2014]
- Uniqure Gene Therapy Info. - Video - April 25th, 2014 [April 25th, 2014]
- Jean Bennett on gene therapy as a treatment for blindness - Video - April 25th, 2014 [April 25th, 2014]
- mice-science-AFPrelax-250414.jpg - April 26th, 2014 [April 26th, 2014]
- Cochlear implant enhances patient experience through gene therapy - April 28th, 2014 [April 28th, 2014]
- Gene therapy may help hearing - April 28th, 2014 [April 28th, 2014]
- Ethics of Gene therapy - Video - April 30th, 2014 [April 30th, 2014]
- Novel Financing For Gene Therapy Company - May 1st, 2014 [May 1st, 2014]
- Gene Therapy To Enhance Hearing - ABC Austrlia News - 2014 - - Video - May 1st, 2014 [May 1st, 2014]
- Biotechnology - GMO's & Gene Therapy - Video - May 1st, 2014 [May 1st, 2014]
- Cochlear Implant Gets an Upgrade with Gene Therapy - Video - May 4th, 2014 [May 4th, 2014]
- Gene therapy for haemophilia - Professor Amit Nathwani - Video - May 4th, 2014 [May 4th, 2014]
- Retrovirus in Gene Therapy - Video - May 4th, 2014 [May 4th, 2014]
- Regeneron, Avalanche To Develop Novel Gene Therapy Products In Ophthalmology - May 5th, 2014 [May 5th, 2014]
- Gene Therapy Used to Preserve Sight in Patients - May 5th, 2014 [May 5th, 2014]
- SCID gene therapy class - Video - May 6th, 2014 [May 6th, 2014]
- Gene Therapy using SMaRT - Video - May 6th, 2014 [May 6th, 2014]
- gene therapy video - Video - May 9th, 2014 [May 9th, 2014]
- Chronic Granulomatous Disease (CGD) - Video - May 12th, 2014 [May 12th, 2014]
- Gene Therapy (Breast Cancer) - Video - May 12th, 2014 [May 12th, 2014]
- Suicide gene therapy - Video - May 12th, 2014 [May 12th, 2014]
- Employment of gene therapy in depression (psychiatric disorder) - Video - May 12th, 2014 [May 12th, 2014]
- Gene therapy for blindness (2012) - Video - May 12th, 2014 [May 12th, 2014]
- AGRC1020 Video Presentation Gene Therapy restores colour vision in monkeys - Video - May 12th, 2014 [May 12th, 2014]
- gene therapy~3 - Video - May 12th, 2014 [May 12th, 2014]
- Gene Delivery System (In-vivo and Ex-vivo) HD - Video - May 12th, 2014 [May 12th, 2014]
- Spark Therapeutics to open headquarters in West Philadelphia - May 14th, 2014 [May 14th, 2014]
- Gene Therapy - Nature - May 14th, 2014 [May 14th, 2014]
- Gene therapy for RTT syndrome benefits and drawbacks - Video - May 16th, 2014 [May 16th, 2014]
- Gene Therapy (Using Biolistic gene gun for gene delivery) - Video - May 16th, 2014 [May 16th, 2014]
- Germline Gene Therapy - Video - May 16th, 2014 [May 16th, 2014]
- Gene Therapy Biology Project for Swavely - Video - May 16th, 2014 [May 16th, 2014]
- Gene therapy extends survival in an animal model of spinal muscular atrophy - May 22nd, 2014 [May 22nd, 2014]
- Novel RNAi therapy silences mutated Huntington's disease gene and reduces symptoms - May 22nd, 2014 [May 22nd, 2014]
- Global Gene Therapy Market: Analysis, Size, Share, Growth, Trends and Forecast 2013 - 2019 - May 22nd, 2014 [May 22nd, 2014]
- Gene therapy hits blood cancers hard - May 22nd, 2014 [May 22nd, 2014]
- Spark Therapeutics late-stage gene therapy for inherited blindness takes a $73M step forward - May 31st, 2014 [May 31st, 2014]
- Genome Editing to Reverse Bubble Boy Syndrome - May 31st, 2014 [May 31st, 2014]
- Genetic Researching: Gene Therapy - Video - May 31st, 2014 [May 31st, 2014]
- BEYOND THE BUBBLE: 10 Years of Gene Therapy - Video - May 31st, 2014 [May 31st, 2014]
- Gene Therapy Combined with IMRT Found to Reduce the Rate of Positive Prostate Biopsy After Treatment for Intermediate ... - June 4th, 2014 [June 4th, 2014]
- Gene therapy combined with IMRT found to reduce recurrence for select prostate cancer patients - June 4th, 2014 [June 4th, 2014]
- Bluebird, Agios: Preview of Next Week's Important Pipeline Updates - June 12th, 2014 [June 12th, 2014]
- Attack of the B - Team EP8 - Drowning for Science! - Video - June 12th, 2014 [June 12th, 2014]
- 3rd International Conference and Exhibition on Cell & Gene Therapy - Video - June 14th, 2014 [June 14th, 2014]
- Blood Disorder Patients Respond Strongly to Bluebird Bio Gene Therapy - June 15th, 2014 [June 15th, 2014]
- Gene Therapy Partnering Terms and Agreements - Video - June 15th, 2014 [June 15th, 2014]
- Gene Therapy - GMAT Free - GFSC120 - Video - June 18th, 2014 [June 18th, 2014]
- New Gene Therapy Rapidly Helps Patients With Rare Blood Disorder - Video - June 18th, 2014 [June 18th, 2014]
- Isis Could Get a $2 Billion Gain From Heart Attack Trials - June 22nd, 2014 [June 22nd, 2014]
- Gene Therapy for Beta Thalassemia - Video - June 22nd, 2014 [June 22nd, 2014]
- A level. R.7. Cystic fibrosis and gene therapy (Ms Cooper) - Video - June 24th, 2014 [June 24th, 2014]
- Gene therapy for rare seeing impairment disorder shows promise for wider use, doctors say ,mesotheli - Video - June 24th, 2014 [June 24th, 2014]