Standard prostate cancer treatments reduce blood levels of testosterone, the hormone that fuels the cancer’s growth. However, most prostate cancers eventually become resistant to these treatments. Such cancers are called castration-resistant prostate cancers. Abiraterone acetate is designed to treat these tumors by inhibiting the production of androgen in the testes, adrenal glands, and prostate cancer tumors themselves.
The clinical trial included 1,195 patients from 13 countries whose metastatic prostate cancer had previously been treated with one of two chemotherapy regimens that included docetaxel . Among the 797 patients randomly assigned to receive abiraterone acetate plus the corticosteroid prednisone , median overall survival was 14.8 months. Among the 398 who received prednisone plus placebo, median survival was 10.9 months.
Differences between the placebo and treatment groups also emerged for all of the trial’s secondary endpoints , including the time that it took for prostate-specific antigen (PSA) levels to increase, progression-free survival according to medical imaging, and the number of patients who experienced reductions in PSA levels after treatment. The benefits of abiraterone were determined during a prespecified interim analysis of the study results, prompting the trial’s Independent Data Monitoring Committee to recommend unblinding the trial and offering abiraterone acetate to patients in the placebo arm.
“This is a major step forward in prostate cancer therapeutics,” said principal investigator Dr. Johann de Bono of the Institute of Cancer Research and the Royal Marsden Hospital in the United Kingdom. “Men with metastatic…castration-resistant prostate cancer have a poor prognosis, with only about one in three alive 5 years after diagnosis,” he explained. “For many men, abiraterone acetate can extend life.”
Similar Early-phase Trials Prohibit Different Drugs, Undermining Outcomes
Researchers speaking at the recent ESMO meeting reported “very high rates of unexplained inconsistencies” in the lists of drugs that patients are cautioned against or prohibited from taking while enrolled in phase I and phase II cancer clinical trials that were conducted in North America. Variability in such lists could make it harder to assess and compare study outcomes, they noted, and could compromise patient safety because of possible interactions between the experimental drug and other drugs the patients may be taking. The findings were presented on October 11 in Milan by Dr. Benoit You of Hospices Civils de Lyon in France and Dr. Eric Chen from Princess Margaret Hospital in Canada.
The researchers reviewed protocols for 100 phase I and phase II cancer trials conducted between 2004 and 2009, 77 of which included lists of cautioned or prohibited drugs. As just one example of the problem, they noted that 37 of these trials were studying similar experimental cancer drugs that are metabolized by the liver enzyme CYP3A4, and yet the lists of cautioned or prohibited drugs that should be avoided because they could interfere with this enzyme’s function ranged in size from one drug to up to 152 drugs.
“We believe that inconsistency among lists of drugs may introduce a source of heterogeneity in patient eligibility, in management of study patient symptoms, and thereby in outcomes” of early-phase trials, said Dr. Benoit in a news release. “As a result, it might impact the comparability of different trials.”
Such confusion, the researchers said, is unlikely to have caused harm to patients, “but it may have significantly reduced the overall quality” of the trial results, and thus had an effect on new drug development. “The development of realistic consensual standardized lists of cautioned and prohibited drugs is warranted,” they said.
Surgical Procedure Reduces Disability and Pain Caused by Spine Fractures in Cancer Patients
A surgical technique known as balloon kyphoplasty (BKP) reduces pain and disability due to compression fractures of the spine in cancer patients, according to results of a randomized trial presented October 9 at the ESMO meeting in Milan, Italy. Compression fractures of the spine, which occur when bones in the spine become brittle, are a significant cause of pain and disability in many patients with multiple myeloma or with cancers that have metastasized to the spine.
A multinational research team led by Dr. Leonard Bastian of Klinikum Leverkusen, Germany, followed 134 adults with cancer, who had fewer than three painful vertebral compression fractures (VCFs), and randomly assigned them to receive either BKP (70 patients) or nonsurgical management (64 patients). Patients who had the surgery showed statistically significant reduced levels of disability after 1 month, as assessed by a questionnaire designed to measure disability, and also had significant improvement in back pain 1 week after surgery. Patients who received nonsurgical management showed no improvement in disability or back pain.
After 1 month, patients who had been randomly assigned to nonsurgical management were given the opportunity to receive BKP, and 38 chose to do so. The researchers followed all patients for 12 months and found that all those who underwent BKP reported continued improvements in back pain, activity level, and quality of life over the study period. The number of adverse events was similar between groups.
With BKP, a surgeon inserts a small balloon through a 1 cm incision into the fractured vertebra and inflates the balloon to temporarily restore the shape and height of the vertebra. The surgeon then deflates and removes the balloon and injects a quick-setting bone cement into the vertebral body—the large, roughly cylindrical part of the vertebra—to stabilize it.
BKP “may be the right treatment option for vertebral compression fractures if conventional pain medication has not been effective or has too many side effects,” said Dr. Bastian in an ESMO news release.
“As research into this technique continues, it will be important to conduct double-blind, placebo-controlled studies to identify the place of balloon kyphoplasty in cancer care,” Dr. Fausto Roila of Ospedale Santa Maria, Terni, Italy, commented in the press release.