New Cancer Vaccine Explored as Potential Treatment for Prostate Cancer Patients with Rising PSA

The gist: A new vaccine treatment  called Prostvac might help treat advanced prostate cancer patients whose tumors are resistant to hormone therapy and who have had either surgery or radiation. Prostvac boosts a patient’s own immune system to fight cancer.  A small clinical trial showed that Prostvac is safe and can be given to patients earlier. More research is needed to see just how well the vaccine works.

“Aiming to increase treatment options for prostate cancer patients who have an early relapse, investigators from a multi-institutional cooperative group — including Rutgers Cancer Institute of New Jersey — have demonstrated that a vaccine therapy that stimulates the body’s own immune defenses can be given safely and earlier in the course of prostate cancer progression.

“As part of a Phase II clinical trial, adult patients with advanced prostate cancer (as evidenced by two rising prostate-specific antigen or PSA values and no visible metastasis) whose cancer is resistant to hormone therapy and had either surgery or radiation were recruited from member institutions in the ECOG-ACRIN Cancer Research Group. In their work, published in the current online edition of European Urology, ECOG-ACRIN investigators examined two different experimental treatment options.

“In step one, patients were treated with PROSTVAC-V/TRICOM and PROSTVAC-F/TRICOM. PROSTVAC-V is derived from a vaccinia virus that was used for many years to vaccinate against smallpox. This virus is modified to produce a PSA protein that helps focus the body’s immune response to the PSA in the prostate tumor. In addition, it is modified to produce three other proteins that help increase an immune cell’s ability to destroy its target (TRICOM). PROSTVAC-F is made from the fowlpox virus, which is found in birds and not known to cause any human disease. It contains the same genetic material as PROSTAC-V, but is given multiple times to further boost the body’s immune system.”


Anastrozole Beneficial for Postmenopausal Women with Lobular Breast Cancer

The gist: A clinical trial compared postmenopausal breast cancer patients who took tamoxifen after surgery with patients who took tamoxifen plus the drug anastrozole. They researchers found that, after three years, more women with lobular breast cancer who took anastrozole were alive than those who took only tamoxifen. These results suggest that anastrozole may benefit postmenopausal women with lobular breast cancer.

“The survival benefit postmenopausal patients with breast cancer derive from anastrozole vs. tamoxifen varies considerably by histology, according to an analysis of phase 3 study results presented at the San Antonio Breast Cancer Symposium.

“Researchers suggested the finding may help refine adjuvant endocrine treatment decisions.

“Several prior studies showed aromatase inhibitors improved outcomes among postmenopausal patients with breast cancer compared with tamoxifen monotherapy. A meta-analysis by Forbes and colleagues, which included data on 11,798 patients included in randomized trials that compared 5 years of tamoxifen vs. a sequence of tamoxifen followed by aromatase inhibitors, showed patients assigned aromatase inhibitors demonstrated a significant reduction in recurrence (RR=0.84; 95% CI, 0.73-0.97). Researchers also observed significantly fewer deaths in the aromatase inhibitor group (RR=0.84; 0.73-0.97)…

“ ‘In summary, among all patients with lobular cancer, anastrozole was associated with a significant reduction in OS events compared to tamoxifen,’ Knauer said. ‘However, anastrozole efficacy was strongly depending on histology and intrinsic subtype of breast cancer.’ ”


Combining Drugs May Help Fight Drug Resistance in Breast Cancer

Note: This article describes research that was done in a laboratory setting, and not in people. However, the drug combination (ganetespib plus hormone therapy) is being tested in patients in clinical trials.

“US researchers have found that combining conventional hormone therapy with an experimental cancer drug helped overcome drug resistance in breast cancer cells in the lab.

“The research focused on a molecular ‘Sherpa’ that helps cells adapt to stressful environments, known as heat-shock protein 90 (HSP90)…

“Trials of ganetespib in combination with hormone therapy are now underway in the US, and the researchers are hoping to see results within the next few years.”


Too Few Prostate Cancer Patients Get Bone-Strengthening Meds: Study

“Many men on hormone therapy for prostate cancer aren’t getting bone-strengthening drugs they may need, new Canadian research contends.

“Hormone therapy, which suppresses male hormones called androgens, helps stop cancer cells from growing. But one consequence of the treatment is weakening of the bones, which can lead to fractures. To reduce this risk, men can be given oral bisphosphonates, such as Fosamax, or an intravenous treatment once a month or once a year with similar drugs, such as Reclast.

” ‘There seems to be a clear mismatch between Canadian guidelines regarding bisphosphonate usage in men undergoing hormone therapy for prostate cancer and actual clinical practice,’ said lead researcher Dr. Shabbir Alibhai, a senior scientist at the University Health Network in Toronto.

“While the low rates of bisphosphonate prescriptions may be appropriate for patients who are at low risk for fracture, most men with osteoporosis or other bone conditions should be taking a bisphosphonate, he said.”


Galeterone Shows Activity in a Variant Form of Castration-Resistant Prostate Cancer

The gist: A drug called galeterone might help lower PSA levels in certain men with castration-resistant prostate cancer (CRPC). A clinical trial recently tested the treatment in volunteer patients.

“Results from a trial of the anti-cancer drug galeterone show that it is successful in lowering prostate-specific antigen (PSA) levels in men with a form of prostate cancer that is resistant to treatment with hormone therapy (castration-resistant prostate cancer or CRPC).

“Associate professor Mary-Ellen Taplin, of the Dana-Farber Cancer Institute, Boston, USA, will tell the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain, today (Wednesday) that galeterone was well tolerated by patients in the ARMOR2 trial, and also lowered PSA levels in a subset of men with CRPC that was resistant to other drugs that target the cancer, such as enzalutamide and abiraterone.

” ‘Recent data have shown that a variant of the androgen receptor called AR-V7, found in tumour cells circulating in the blood of patients with metastatic CRPC, predicted resistance to treatment with enzalutamide and abiraterone,’ she will say. ‘Indeed, we believe AR-V7 and other, related variants are a mechanism of resistance in this disease and patients who have them may have a poorer prognosis.’ ”


Prostate Cancer Medications Linked with Increased Risk of Heart-Related Deaths in Men with Cardiovascular Problems

“A new study has found that certain prostate cancer medications are linked with an increased risk of dying from heart-related causes in men with congestive heart failure or prior heart attacks. Published in BJU International, the findings will help doctors and patients weigh the benefits and risks of the drugs.

“Androgen deprivation therapy (ADT), which reduces levels of male hormones in the body to prevent them from stimulating cancer cells, is a mainstay of treatment for prostate cancer. Despite its anticancer effects, ADT has been associated with heart problems, including increased risk of diabetes, coronary heart disease, heart attacks, and sudden cardiac death. To investigate this potential link thoroughly, Paul Nguyen, MD, of the Dana-Farber/Brigham and Women’s Cancer Center in Boston, along with David Ziehr of Harvard Medical School and their colleagues, analyzed information on 5,077 men with prostate cancer who were treated between 1997 and 2006. Thirty percent of these men received ADT, while the others did not.

“After a median follow-up of 4.8 years, no association was detected between ADT and heart-related deaths in men with no cardiac risk factors (1.08 percent at five years for ADT versus 1.27 percent at five years for no ADT) or in men with diabetes, hypertension, or high cholesterol (2.09 percent vs 1.97 percent). However, ADT was associated with a 3.3-times increased risk of heart-related deaths, in men with congestive heart failure or prior heart attacks. In this subgroup, heart-related deaths occurred in 7.01 percent of men receiving ADT versus 2.01 percent of men not receiving after five years. This suggests that administering the therapy to 20 men in this potentially vulnerable subgroup could result in one cardiac death.

” ‘While androgen deprivation therapy can be a lifesaving drug for men with prostate cancer and significantly increase the cure rates when used with radiation for aggressive disease, this study also raises the possibility that a small subgroup of men who have significant heart disease could experience increased cardiac death on ADT,’ said Dr. Nguyen. He noted that because the study was retrospective, it must be carefully weighed against larger controlled trials that have demonstrated the benefits of ADT. ‘I would still say that for men with significant heart problems, we should try to avoid ADT when it is not necessary—such as for men with low-risk disease or men receiving ADT only to shrink the prostate prior to radiation. However, for men with high-risk disease, in whom the prostate-cancer benefits of ADT likely outweigh any potential cardiac harms, ADT should be given even if they have heart problems, but the patient should be followed closely by a cardiologist to ensure that he is being carefully watched and optimized from a cardiac perspective.’ “


Subsidies Help Breast Cancer Patients Adhere to Hormone Therapy

“A federal prescription-subsidy program for low-income women on Medicare significantly improved their adherence to hormone therapy to prevent the recurrence of breast cancer after surgery.

” ‘Our findings suggest that out-of-pocket costs are a significant barrier’ to women complying with hormone therapy, said Dr. Alana Biggers, assistant professor of clinical medicine at the University of Illinois at Chicago College of Medicine, and lead investigator on the study. Programs that lower these costs can ‘improve adherence—and, hopefully, breast cancer outcomes—for low-income women,’ she said. Biggers presented the results of the study at an Oct. 14 press conference in advance of the American Society for Clinical Oncology Quality Care Symposium in Boston.

“Breast cancer is a leading cause of cancer-related deaths for women of all races, but survival rates differ by race and socioeconomic status, with African American women and women of low income having higher rates of death.”


Hormones After Breast Cancer: Not Fuel for the Fire After All?

Editor’s note: This study used mice in a lab to explore the question of whether hormone therapy can improve survival and quality of life for postmenopausal women diagnosed with breast cancer. The results were promising, but more research needs to be done.

“A new study supports a growing body of research suggesting a safe and effective role for natural steroid hormones in treating postmenopausal breast cancer, with fewer detrimental side effects and improved health profile than with standard anti-hormone therapies. The study will be published in final format today in the open-access journal Reproductive Biology and Endocrinology.

“Breast cancer is the most frequently diagnosed cancer in women in the United States. Approximately 70% of breast cancers are diagnosed in postmenopausal women. Major clinical trials and experimental studies showed that a class of anti-estrogen drugs called aromatase inhibitors (AIs) is effective against postmenopausal . Yet despite their effectiveness in reducing tumor recurrence, aromatase inhibitors have adverse effects on the cardiovascular system and increase osteoporosis and bone fractures, which may explain their lack of overall survival improvement versus the older treatment, tamoxifen. These effects, together with undesirable side effects such as incontinence and bone and joint pain, cause many women to discontinue using AIs. Alternatives are needed.

“In their study, researchers at the Center of Excellence in Cancer Research at the Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, set out to explore a radical and counterintuitive hypothesis: Could an optimal choice of hormones lead to improved survival factors and quality of life, enough to outweigh any negative effect on tumor recurrence? Radical—because current standard of practice considers hormone treatment of any type absolutely contraindicated following hormone-receptor-positive breast cancer. Counterintuitive— because estrogen-blocking aromatase inhibitors, a nearly opposite treatment, are the current adjuvant treatment for women after hormone-sensitive breast cancer.

“Results from this study in a mouse model suggest the answer to their question is ‘yes,’—well-chosen hormones could improve both survival and quality of life.”


Study Discounts Testosterone Therapy for Early Prostate Cancer

“For decades, millions of men with early prostate cancer have been placed on drug therapy to suppress their production of testosterone, despite such significant side effects as impotence, diabetes and bone loss. Now a large new analysis has concluded that so-called androgen deprivation therapy does not extend the lives of these patients.

“ ‘There are so many side effects associated with this therapy, and really little evidence to support its use,’ said Dr. Grace L. Lu-Yao, a researcher at the Rutgers Cancer Institute of New Jersey and the lead author of the report, published on Monday in JAMA Internal Medicine. ‘I would say that for the majority of patients with localized prostate cancer, this is not a good option. ”

“Dr. Lu-Yao and her colleagues followed tens of thousands of men with early prostate cancer for as long as 15 years and found that those who received androgen deprivation therapy lived no longer on average than those who did not. The study joins a growing body of evidence indicating that for many men with early prostate cancer, avoiding testosterone-suppressing drugs altogether may be better than grappling with their potentially devastating toll.”

“One expert who was not involved in the new study, Dr. James M. McKiernan, acting chairman of urology at NewYork-Presbyterian Hospital/Columbia University Medical Center said its findings were ‘eye-opening and even alarming.’ ”

Image: Credit Stuart Bradford