CE lesson worth 1.0 contact hour that is intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients.
The overall goal is to update the healthcare professional’s knowledge of cancer detection and prevention and to understand current and new research regarding state-of-the-art care for those with or at risk for cancer.
Intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients.
Upon completion, participants should be able to:
Dannemiller is approved by the California Board of Registered Nursing, Provider Number 4229, for 1.0 contact hour. CBRN credit is not accepted by the Michigan and Utah State licensing boards.
The planners and authors of this CE activity have disclosed no relevant financial relationships with any commercial companies pertaining to this activity.
This activity is provided free of charge to participants.
The combination of palbociclib and letrozole more than doubled progression-free survival (PFS) and showed a promising 4.2-month trend toward improvement in overall survival (OS) for patients with estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer, according to results from the phase II PALOMA-1 trial that were presented at the 2014 American Association for Cancer Research (AACR) Annual Meeting. Abstract CT101
In the 165-patient open-label study, the CDK 4/6 inhibitor palbociclib improved PFS by 20.2 months compared with 10.2 months for letrozole. The median OS was 37.5 months with palbociclib compared with 33.3 months with letrozole. This first analysis of OS contained data from 61 patients (37%) and was not deemed statistically significant. A follow-up analysis of OS will be conducted once more events have accrued.
“The palbociclib and letrozole combination demonstrated a significantly improved clinical outcome for patients who had hormone receptor-positive, metastatic breast cancer in this phase II trial,” said Finn, an associate professor of medicine at the University of California, Los Angeles (UCLA).
“This study grew out of a strong initial preclinical observation made a few years ago that HR-positive breast cancer cells are dependent on CDK-4/6 for their growth, and that these cancers are sensitive to inhibition of CDK- 4/6,” he continued. “Further a small, lead-in, phase I study conducted prior to this phase II trial showed that palbociclib and the antiestrogen drug letrozole could be given safely as a combination, with manageable side effects and also showed preliminary signs of good efficacy.”
In the phase II study, continuous letrozole was administered at a 2.5-mg daily dosage with or without 125-mg daily palbociclib for 3 weeks followed by 1 week of rest until progression. A totoal of 165 postmenopausal patients with ER-positive, HER2-negative advanced breast cancer were randomized in a 1:1 ratio in two parts: part 1 contained 66 patients and part 2 had 99 patients. The primary endpoint was PFS by investigator assessment.
In the final analysis for PFS, the HR in Part 1 was 0.299 (95% CI, 0.156-0.572; P = .0001) and the HR in part 2 was 0.508 (95% CI, 0.303-0.853; P = .0046), for letrozole plus palbociclib compared with letrozole alone, respectively. For the two parts combined, the HR was 0.488 (95% CI, 0.319-0.748; P = .0004). Patients in part 2 tested positive for CCND1 amplification and/or loss of p16, as possible markers of sensitivity to palbociclib. However, a correlation between these markers and outcomes was not found.
In an interim analysis of the PALOMA-1 study presented in 2012 at San Antonio Breast Cancer Symposium, the combination resulted in a response rate of 45% compared with 31% for the monotherapy and the overall clinical benefit rate was 70% versus 44%.
The most commonly reported treatment-related adverse events in the combination arm were neutropenia, leukopenia, anemia, and fatigue. Altogether, 13% of patients discontinued treatment as a result of side effects in the palbociclib arm compared with 2% for letrozole.
“This is an exciting data set that shows a major clinical benefit for patients who have hormone receptor-positive, metastatic breast cancer,” said the study’s coauthor, Dennis Slamon, MD, PhD, professor of medicine and director of the Revlon/UCLA Women’s Cancer Research Program.
“The potential impact of this study could be huge. We are doing further phase III work with the drug, but the current data are as exciting as the initial studies we were involved in when testing Herceptin for HER2-positive breast cancers,” he continued.
In a discussion of the results, Jose Baselga, MD, PhD, the physician-in-chief at Memorial Sloan Kettering Cancer Center and president-elect of AACR, called the results promising but cautioned against too much early optimism.
He noted that several agents, including the PARP inhibitor iniparib, demonstrated promising phase II results and then were not successful in phase III studies. However, if these phase II results were duplicated in a larger clinical trial, palbociclib would become the standard of care for patients with ER-positive metastatic breast cancer, Baselga believes.
Palbociclib is under investigation in a number of phase III clinical trials. The PALOMA-2 investigation is exploring treatment with letrozole in combination with palbociclib versus letrozole alone as a frontline treatment for postmenopausal women with ER-positive, HER2- negative advanced breast cancer (NCT01740427).
Additionally, the PALOMA-3 trial is exploring palbociclib in combination with fulvestrant compared with fulvestrant alone in women with hormone receptorpositive, HER2-negative metastatic breast cancer whose disease has progressed after prior endocrine therapy (NCT01942135).
Two recently published clinical studies demonstrated a strong association between higher levels of vitamin D and improved outcomes among patients with various cancers.
In one study, researchers from the Institute for Nutritional Sciences at the Shanghai Institutes for Biological Sciences in China examined circulating 25-hydroxyvitamin D [25(OH)D] levels among 17,332 patients with different tumor types across 25 studies. Vitamin levels were measured at or near diagnosis (J Clin Endocrinol Metab. doi:10.1210/jc.2013-4320).
Overall, the meta-analysis showed that a 10-nmol/L increase in circulating 25(OH)D levels was linked to a 4% improvement in overall survival.
The strongest association between vitamin D levels and improved overall survival (OS) was observed in patients with colorectal cancer, breast cancer, and lymphoma. In these groups, the pooled HR for OS for the highest versus the lowest quartile of circulating 25(OH)D levels was 0.55, 0.63, and 0.48, respectively. A positive correlation was also observed in patients with lung cancer, gastric cancer, prostate cancer, leukemia, melanoma, or Merkel cell carcinoma; however, the connection was not as strong.
In a second study, researchers found that men at high risk of prostate cancer who had a vitamin D deficiency are more likely to have aggressive disease at diagnosis (Clin Cancer Res. 2014;20(9):2289-2299).
The researchers examined serum 25(OH)D levels in 667 high-risk men who were screened for vitamin D deficiency prior to receiving their first prostate biopsy. The men, aged 40 to 79 years, had elevated PSA levels and other prostate cancer risk factors.
“This is the first study to look at vitamin D deficiency and biopsy outcomes in men at high risk of prostate cancer,” said senior author Rick Kittles, associate professor in the department of Medicine at the University of Illinois at Chicago. “Previous studies focused on vitamin D levels in men either with or without prostate cancer.”
Among the study population, African American men with 25(OH)D <20 ng/mL had 2.43 increased odds of receiving a prostate cancer diagnosis of any stage (P = .01). Additionally, African American men with 25(OH)D <12 ng/mL were 4.89 times more likely to have a Gleason score ≥4+4 (P = .006) and 4.22 times more likely to have a tumor stage ≥cT2b (P = .003).
European-American men with 25(OH)D <12 ng/ mL were 3.66 times more likely to have a Gleason score ≥4+4 (P = .008) and 2.42 times more likely to have a tumor stage ≥cT2b (P = .008).
The increased odds for aggressive disease among patients with vitamin D deficiency were established after adjusting for potential confounding factors, including obesity, smoking, family history, diet, and calcium intake.
“Vitamin D deficiency could be a biomarker of advanced prostate tumor progression in large segments of the general population,” said leader author Adam B. Murphy, MD, assistant professor in Urology at Northwestern University Feinberg School of Medicine, in a statement. “More research is needed, but it would be wise for men to be screened for vitamin D deficiency and treated.”
Laura Newton, MA, RD
Department of Nutrition SciencesUniversity of Alabama at BirminghamBirmingham, AL
These studies not only demonstrate the benefit of higher vitamin D levels in certain types of cancer survival, but also highlight the overall prevalence of vitamin D deficiency. According to the National Health and Nutrition Examination Survey (NHANES) in 2005 to 2006, 41% of adults that participated in the survey had 25-hydroxyvitamin D levels below 20 ng/ mL (50 nmol/L).1 While the optimal serum level remains controversial, experts do agree that levels lower than 20 ng/mL are suboptimal (some feel the cutoff should be 30 ng/mL). Commonly associated with its role in bone health and calcium/phosphorus utilization, vitamin D is also thought to play a role in development of cancer through communication with cells to promote cellular differentiation, stimulate apoptosis, and decrease cancer cell growth.
Commonly thought of as the “sunshine” vitamin, skin exposed to sunlight can make vitamin D. Only a handful of foods are good sources of vitamin D. These include fatty fish (salmon, tuna, sardines), fish liver oils such as cod liver oil, eggs, and foods that have been fortified with vitamin D such as milk and some cereals and juices. The recommended daily allowance for vitamin D up to age 70 years is 600 IU/day and increases to 800 IU/day for those older than 70. A fat-soluble vitamin, there is risk of toxicity if taken in excess. The upper limit is currently set at 4000 IU/day.
There are several causes of vitamin D deficiency, including decreased intake, altered absorption (cystic fibrosis, celiac disease, Crohn’s disease, etc), little sun exposure, and decreased endogenous synthesis. Particularly those with little sun exposure and/or those living in the northern latitudes may be at risk for deficiency. Synthesis in the skin may also be affected by increasing age, the time of day receiving sun exposure, sunscreen use, length of sun exposure, and skin color (darker skinned people need longer sunlight exposure to trigger vitamin D production).
Being overweight or obese may also contribute to vitamin D deficiency as it then is absorbed into body fat instead of blood.
While much more research is needed on the role of vitamin D in cancer development, optimal serum levels, and the potential use of supplementation in cancer prevention and/or treatment, we should promote dietary intake of foods high in vitamin D and screening of those at risk for deficiency.
1. Forrest KY, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res. 2011;31(1):48-54.
approach using heat to alleviate the pain commonly associated with bone metastases has proven to be safe and effective in a multicenter phase III clinical trial, yielding a 64% response rate based on self-reported pain scores among patients receiving the noninvasive intervention. The study was published online ahead of print April 23, 2014 in the Journal of the National Cancer Institute.
“This is the first phase III study to use this technology in the treatment of cancer,” said lead study author Mark Hurwitz, MD, director of Thermal Oncology in the Department of Radiation Oncology at Thomas Jefferson University in Philadelphia. “It’s clear that for many of these patients, pain has a major impact on their everyday lives. This approach offers a new way to help alleviate that pain via an outpatient, noninvasive procedure.”
For this international study, 147 patients receiving treatment at 17 centers were randomized 3:1 to receive MRI-guided focused ultrasound (MRg- FUS; n = 112) or placebo (n = 35). To be eligible for the study, patients had ≤5 painful lesions and a life expectancy of ≥3 months. In addition, eligible participants were either experiencing painful bone metastases despite previous treatment with radiation (RT), were inappropriate to receive further RT, or had refused RT.
MRgFUS was performed on a device-accessible targeted tumor (eg, in the ribs, extremities [excluding joints], pelvis, shoulders, or spinal vertebra), with the ultrasound used to heat the tumor tissue to between 65ËšC and 85ËšC during the ablation phase. MRI was deployed to target the correct tumor and thus spare surrounding normal tissue and organs. Time inside the scanner was an average of 176 ± 57 minutes, and average sonication time (both low-energy subtherapeutic and ablative) was 83 ± 43 minutes.
Patients in the placebo arm had the same procedure, but the ultrasound device was not activated— an approach that researchers said made the blinding of placebo patients very effective.
Composite change in self-reported pain scores without an increase in pain medication was the study’s primary endpoint, based on assessments at baseline and 3 months, using the Numerical Rating Scale for pain (NRS) and Morphine Equivalent Daily Dose (MEDD) measure. Patients experiencing at least a two-point decrease in worst NRS and whose MEDD did not go up >25% were considered responders for the purposes of the study.
Seventy-two patients in the treatment arm (64.3%) were responders, compared with 20% of patients receiving placebo treatment at 3 months (P <.001). Of responders in the MRgFUS arm, 23.2% achieved complete response by the conclusion of the trial, reporting a worst NRS pain score of 0, versus 5.7% of patients in the placebo arm. Patients who did not respond to placebo in ≤2 weeks could be unblinded to the MRgFUS intervention, and 70.7% of placebo crossover patients had a statistically significant pain response.
Notably, said the researchers, most patients receiving MRgFUS experienced pain relief and improved functioning within several days of treatment, and many were able to reduce or stop use of opioid medications.
Statistically significant differences between the two arms were sustained at each subsequent timepoint throughout the trial.
The most common adverse event (AE) reported with the MRgFUS approach was pain during the procedure experienced by approximately onethird of patients in the experimental arm who reported pain that was either mild (6.2%), moderate (10.7%), or severe (15.2%).
Study authors noted that 60.3% of all adverse events (AEs) resolved on the day of treatment. Two patients had fractures, a rate that compares favorably with the fracture risk associated with RT.
Hurwitz said that the next steps for this research will be to refine the treatment technique to get an even better response rate and to apply radiation and thermal therapy in combination to treat bone metastases, noting that the combination has demonstrated clinical benefits for treating other malignant conditions.
David Leos, RN, MBA, OCN
Clinical Research Nurse Supervisor
Department of Radiation OncologyUT MD Anderson Cancer CenterHouston, TX
The announcement of this new potential and noninvasive treatment should be welcome news to those familiar with the limitations of currently available treatments for patients suffering due to bone metastasis. While radiation therapy is a mainstay for such cases, the described MRgFUS approach seems to offer desirable and fairly rapid results when radiation is, for whatever reason, not an option.
The preparation and implementation time seems to offer an advantage over the treatment planning required for radiation, and its integrated use of MRI allows for conformal treatment fields that spare surrounding normal tissue which mimics conformal techniques used in radiation therapy. Not mentioned in the article is whether retreatment, if needed with this technique, is possible versus the typical limitations of radiation in having to avoid prior treatment fields.
One dilemma with using radiation for bone metastasis is the question of what is optimal fractionation for palliation. The literature varies on this. Prior work has investigated using a single dose versus the standard multiple fractions. In this and other studies, effective palliation of pain has been achieved; however, the retreatment rate has been reported to be higher.
Utilizing the MRgFUS technique is reported to hold other advantages over ablative treatments in that the results in pain control were rapid and durable and significantly reduced the use of pain medications. As evidenced by the patientreported outcomes, quality of life—and specifically, functional interference from pain—was positively impacted. Additionally, the procedure was generally welltolerated and adverse events few and quite short-lived.
Of note, the rather lengthy average treatment time for MRgFUS may exclude those patients with claustrophobic concerns related to MR imaging, but this Phase III study serves as a proof of concept for the technology as a cancer treatment option.
Androgen-deprivation therapy (ADT) is a mainstay of treatment for prostate cancer in a number of settings, so managing its side effects is becoming increasingly important for urologists and oncology practitioners in collaboration with primary care physicians.
The issue is of particular concern due to the availability of newer agents that decrease testosterone levels for longer periods of time, and also with the use of ADT in nonmetastatic prostate cancers, which ultimately lengthens the time men spend on antiandrogen drugs, according to Leonard G. Gomella, MD, chairman of the Department of Urology at Thomas Jefferson University Hospital in Philadelphia.
ADT can involve bilateral orchiectomy or the use of estrogens, LHRH agonists or antagonists, antiandrogens, newer agents such as abiraterone, or the secondary administration of ketoconazole, Gomella pointed out.
The strategy, he said, is most appropriately used upon diagnosis of metastatic prostate cancer; with radiation in intermediate- to high-risk prostate cancer; to stimulate volume reduction before brachytherapy; and after treatment failure in localized disease, although the timing in that setting is controversial.
With increased use of the strategy have come growing concerns over side effects, including hot flashes, loss of libido, fatigue, anemia, muscle loss, osteoporosis, and bone fracture. Adverse events can also include depression, memory difficulties, and emotionality, as well as metabolic syndrome.
While giving ADT on an intermittent schedule can help ease these side effects, the jury is still out on whether that method is as effective in treating prostate cancer as continuous therapy, Gomella said.
Gomella explained that GnRH agonists increase cholesterol and triglycerides,1 boost obesity, and heighten insulin resistance2 in men with prostate cancer, potentially leading to diabetes mellitus, coronary heart disease, and myocardial infarction.3
To monitor for signs of diabetes, clinicians should conduct blood screens for glycated hemoglobin levels and markers of diabetes and prediabetes in these patients at baseline and then yearly, and should promote weight loss and physical activity,4 Gomella suggested.
Tracking potential cardiovascular complications should involve screening for fasting lipoproteins at baseline, 1 year, and then every 5 years, and assigning a target LDL cholesterol level based on major risk factors for coronary heart disease, Gomella said. Prevention in this setting, should focus on the treatment of hypertension, tobacco cessation efforts, the promotion of healthy lifestyle choices, and the use of first-line statins for hyperlipidemia when needed.4
While a normal man loses 0.5% of his bone density in a year,5 men on ADT lose 4.6% of their bone density in that period,6 a trend that “adds up over the long term and has the potential to cause great morbidity and, in fact, mortality,” Gomella said. After being on these medications for 10 years, 80% of men have osteoporosis,7 he added.
One study found that the likelihood of experiencing a bone fracture between 1 and 5 years after treatment with a GnRH agonist increased 6.8%, to a frequency of 19.4%, in patients with prostate cancer who received ADT compared with patients with the disease who were not treated with ADT; in the ADT group versus the non-ADT group, 5.2% versus 2.4% of patients experienced fractures that required hospitalization.8 Fractures in areas such as the hip can significantly decrease a patient’s longevity, and men fare much worse in that situation than women do, Gomella noted.9
Monitoring bone mineral density (BMD) remains the gold standard for diagnosing osteoporosis in clinical practice, as it is one of the best ways of determining bone strength and predicts fracture as reliably as blood pressure predicts stroke. A DEXA bone scan T-score of <-2.5 indicates osteoporosis, he said. He added that the World Health Organization has a fracture risk assessment questionnaire that practitioners may find helpful.
One simple tactic for prevention is the administration of vitamin D, which at 700 to 800 IU per day can lower the risk of bone fracture by 26%, Gomella said.10
Along with that, calcium can help, but in doses above 1000 IU it comes with a side effect of its own—a 20% increased risk of cardiovascular disease mortality in men, Gomella said.11 As a result, he said, it is now considered best for patients to get about 400 mg of calcium from their diets, with supplementation at a dosage of 600 mg daily.
By inhibiting osteoclast activity, bisphosphonates such as zoledronic acid, pamidronate, alendronate, and risedronate, can reduce bone resorption and turnover, slightly increasing bone mineral density (BMD) in the hips and spine and reducing the incidence of vertebral fractures by 40% to 70%, Gomella said. However, these drugs should not be given if a patient’s glomerular filtration rate is <30 mL/min, and a dental exam should be given before starting, and again every 6 months, to limit the risk of osteonecrosis of the jaw, a potential side effect with this drug class. Other side effects can include dysphagia, nausea, uveitis, hypocalcemia, renal impairment, and musculoskeletal pain.
Some bisphosphonates are approved only for women, he added, and drugs in this class that are approved for men tend to be applicable in very specific settings, such as osteoporosis but no metastases, or vice versa.
Also potentially useful in this population is the monoclonal antibody denosumab (Prolia, Xgeva), which can increase bone density at the spine by 6.7% after 2 years and decrease the incidence of vertebral fractures by 68% and hip fractures by 40%, Gomella said.12,13
Potential side effects include osteonecrosis of the jaw, hypocalcemia, and new primary malignancy, Gomella pointed out.
Other potential treatments for bone metastases and/or osteoporosis include the parathyroid hormone teriparatide, although it is not appropriate for men who have undergone radiation and is typically not used in urology; estrogen or testosterone, which are not FDA-approved in these settings and are controversial; and the nonsteroidal antiestrogen toremifene, which is not FDA-approved for use in men, Gomella said.
To best prevent and track osteoporosis in men taking ADT, doctors should conduct BMD testing on all such patients at baseline, after 1 year of treatment, and then every 2 years, Gomella recommended.
He said that prevention and early treatment should include exercise, prevention of falls, smoking cessation, decreased alcohol intake, 1000 mg a day of calcium, and 1000 IU a day of vitamin D3. Drug therapy should be considered in patients who are aged ≥50 years and fit at least one of the following categories: history of hip or vertebral fracture; T-score of ≤-2.5 at the femoral neck or spine; a 10-year ≥3% probability of hip fracture according to the World Health Organization’s questionnaire; or a 10-year ≥20% probability of a major osteoporosis fracture according to that scale.4
Hot flashes affect 50% to 80% of men taking ADT. Palliative measures should include suggesting that men identify and avoid their hot-flash triggers and keep their environment cool, Gomella said. He added that reassuring patients that hot flashes may subside over time “usually does a lot of good.” While hot flashes can interfere with a patient’s daily activities, Gomella continued, they are difficult to treat because there are no FDAapproved medications for this condition in men, and many of the therapies that are available can result in side effects.
Megestrol acetate at 20 mg/d14 and medroxyprogesterone acetate at 400 mg/d15 have been fairly effective, but cause weight gain, Gomella said. Other treatments being tested or used in this setting include estrogens, antidepressants, neuromodulators, and acupuncture, which so far seems promising for its efficacy and lack of side effects, Gomella said. He added that soy products contain phytoestrogens that might decrease hot flashes and improve cardiac and bone health.
Frank delaRama, RN, MSN, AOCNS
Clinical Nurse Specialist Oncology Genomics
Prostate Cancer Nurse Navigator
Palo Alto Medical FoundationPalo Alto, CA
Prostate cancer treatment can last years to even decades. The best case scenario is when curative treatment with surgery or radiation is successful, never needing anything more than just yearly PSA checks. On the other hand, prostate cancer that is aggressive or recurrent may need ongoing treatment to keep it under control, similar to managing a chronic disease like diabetes. Thankfully, the current state of prostate cancer treatment is often so successful with respect to overall survival, allowing us to turn our attention to maximizing opportunities to improve quality of life.
Androgen-deprivation therapy (ADT) is a common tool used in the prostate cancer care continuum, with disease ranging from localized, intermediate-risk to recurrent or metastatic. The article here provides the oncology nurse some key points on which to focus our ongoing assessment and care for patients on ADT. With metabolic syndrome, bone health, and hot flashes, there are many nursing and medical interventions that are relatively simple, yet with great impact on quality of life.
Basic nursing assessments usually include reviewing lab values, as well as trends in weight and blood pressure. Also integral to nursing intervention are tasks such as educating our patients on healthy diet and lifestyle, encouraging smoking cessation, and management of treatment side effects. Given the findings outlined in this review, there are modifiable risk factors where oncology nurses can have a great impact on patient’s overall health and quality of life, as opposed to medication side effect management alone.
In much of cancer treatment and follow-up care, patients have a relatively passive role, completing imaging and blood tests, or receiving injections and infusions. With teaching points on diet, exercise, and nonpharmacologic side effect self-management, our patients with prostate cancer on ADT can feel more in control—taking an active role within their treatment plan—thanks in part to the nurse.