Clinical Insights: June, 2013

July 10, 2013
Oncology Nursing News

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.

STATEMENT OF NEED

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.

TARGET AUDIENCE

Intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients.

OVERALL EDUCATIONAL OBJECTIVES

Upon completion, participants should be able to:

  • Describe new preventive options and treatments for cancer patients
  • Identify options for individualizing the treatment for cancer patients
  • Review new evidence to facilitate survivorship and supportive care for cancer patients

ACCREDITATION STATEMENT

Dannemiller is approved by the California Board of Registered Nursing, Provider Number 4229, for 1.0 contact hours. RNs outside California must verify with their licensing agency for approval of this course.

DISCLOSURES

The planners and authors of this CE activity have disclosed no relevant financial relationships with any commercial companies pertaining to this activity.

METHOD OF PARTICIPATION

  • Read the articles in this section in its entirety.
  • Go to www.dannemiller.com/onn-june-2013.
  • Complete and submit the CE posttest and activity evaluation.
  • Print your Certificate of Credit.

This activity is provided free of charge to participants.

Hematologic Malignancies

Encouraging Results for Ibrutinib

Ibrutinib was well tolerated and highly effective in eradicating tumor cells in both treatment-naïve and relapsed/refractory patients with chronic lymphocytic leukemia (CLL) in an ongoing phase II study reported at the 2013 Annual Meeting of the American Association for Cancer Research. The drug dramatically reduced disease burden in the lymph nodes, blood, spleen, and bone marrow, and responses were durable. Further, correlative studies confirmed on-target effects of ibrutinib demonstrating sustained inhibition of B-cell receptor signaling and NF-kappa B signaling in both peripheral blood and lymph nodes.

“The degree of tumor reduction achieved by oncedaily oral ibrutinib was impressive. Within just 2 months, we have seen patients with more than 90% reduction of lymph node tumor burden,” said lead author Adrian Wiestner, MD, PhD, of the National Institutes of Health in Bethesda, Maryland.

Ibrutinib is a selective inhibitor of Bruton’s tyrosine kinase (BTK), an element of the B-cell receptor signaling pathway implicated in the evolution of CLL. This study confirms the activity of ibrutinib reported earlier this year at the American Society of Hematology meeting, particularly in patients with deletions of the 17p chromosome, who are known to be difficult to treat, Wiestner commented.

The phase II single-center trial included two cohorts of patients with CLL who required treatment: elderly patients over age 65 years (n=24; 8 treatment- naïve; 16 relapsed/refractory) and those with deletion of chromosome 17p (n=29; 15 treatmentnaïve; 14 relapsed/refractory).

All patients were treated with ibrutinib 420 mg per day in 28-day cycles.

Ibrutinib was safe and well tolerated. The most common adverse events were grades 1 and 2 diarrhea, rash, arthralgia, cramps, mouth sores, and fatigue. Hematologic adverse events were rare, and no treatment-related drug discontinuations were reported. Two deaths occurred, both unrelated to the study drug.

The drug achieved rapid disease control in all anatomic sites at 6 months; 95% of patients achieved at least a 73% reduction in lymph node disease burden, as well as a reduction in splenomegaly (median reduction, 55%). In 26 patients with an available bone marrow biopsy, ibrutinib reduced tumor infiltration by CLL cells by 82%. Absolute lymphocyte count was reduced by a median of 62%. According to standard response criteria for CLL, the rate of partial response was 52%. At 12 months, the estimated event-free survival was 94%.

Abstract LB-141

Nurse Perspective on Treating CLL

Phyllis McKiernan, RN, MSN, APN, OCNNurse PractitionerAdult Blood and Marrow Transplantation DivisionJohn Theurer Cancer CenterHackensack, NJ

Chronic lymphocytic leukemia (CLL) is the second most common adult leukemia, and it is estimated in the United States that over 4500 people will die from the disease this year.1 While many patients can be initially managed with a “watch and wait” approach, patients with advancedstage or high-risk disease typically have a poor response to standard chemotherapy.

Targeted therapies have been shown to be effective in a variety of malignancies, and in some cases have become the standard of care, such as the tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. Ibrutinib, a Bruton’s tyrosine kinase inhibitor, has been shown to be well tolerated and effective in reducing tumor burden in the blood and lymph nodes of patients with CLL. This phase II study included elderly CLL patients with a 17p deletion, both treatment-naïve or relapsed/refractory. The initial dramatic response is encouraging, and it will be interesting to see the duration of response as well as any chronic side effects from the drug.

Future clinical trials can focus on not only the use of ibrutinib as a single agent, but also in combination with other targeted therapies, possibly eliminating the need for toxic chemotherapy. Based on these results, for patients with CLL, ibrutinib can offer a chance for disease control and the potential for improved quality of life.

Reference

1. (2013) SEER Stat Fact Sheets: Chronic Lymphocytic Leukemia. http://seer.cancer.gov/statfacts/html/clyl.html. Accessed May 24, 2013

Adoptive T-Cell Therapy Combined With Vaccine Shows Promise in Difficult-to-Treat Ovarian Cancer

By Anna Azvolinsky, PhD

A two-step immunotherapy approach consisting of adoptive T-cell therapy and a dendritic cell vaccine has shown activity in a phase I advanced ovarian cancer clinical trial. The results were presented at the American Association for Cancer Research (AACR) Annual Meeting 2013 held April 6-10 in Washington, DC, by Lana Kandalaft, PharmD, PhD, assistant professor and director of Clinical Development and Operations at the Ovarian Cancer Research Center at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

All patients had recurrent, progressive, stage 3 or 4 ovarian cancer. Of 31 patients treated with the vaccine, 19 (61%) showed a clinical benefit from the combination immunotherapy. Eight of the 19 patients had no measurable disease at the end of the trial but remained on maintenance vaccine therapy. One patient remains disease-free after 42 months in complete remission.

Ovarian cancer is the fifth leading cause of death from cancer among women. It remains difficult to treat partly because it is typically diagnosed at an advanced stage, and there is a high unmet need for better, more durable treatment of advanced ovarian cancer. The 5-year survival rate for stage 4 invasive epithelial ovarian cancer is approximately 18%.

The new immunotherapy requires a sample of the patient’s tumor taken at the time of surgery in order to create a personalized vaccine. The researchers isolate immune cells called dendritic cells from the tumor sample. Six of the patients in the trial received an initial version of the vaccine, and the subsequent 25 received an optimized version developed at the Penn Ovarian Cancer Research Center. According to Kandalaft, the team is continuing to work to improve the vaccine.

As long as the tumor tissue from the patient is resected at time of surgery in a sterile manner and preserved while the tissue is still alive using cryogenics, the vaccine can be created, according to Kandalaft.

Eleven patients in total were treated with the combination of dendritic cell vaccine and adoptive T-cell therapy. All of these patients initially received the vaccine but still had residual disease and went on to receive adoptive T-cell therapy. The patients’ T-cells were removed from peripheral blood samples, expanded in the laboratory, and then reinjected into the patient. Seven of the 11 patients had stable disease, and one had a complete response.

Analyses showed that because the patients’ immune systems were already primed by the dendritic cell vaccine to attach tumor cells, the subsequent adoptive T-cell transfer magnified the immune response further.

One of the current goals of the research team is to identify what was unique about the patient who achieved complete remission. “The patient had tumor infiltrating lymphocytes in her tumor tissue at time of surgery,” said Kandalaft. Not all patients have evidence of such a spontaneous immune response in the form of immune cells that are able to infiltrate into the tumor. Other patients in the trial who had a clinical benefit also had such a spontaneous immune response.

Both the vaccine and combination immunotherapy treatments were combined with bevacizumab, a monoclonal antibody against vascular endothelial growth factor A (VEGF-A), which blocks blood vessel formation and growth.

Patients tolerated the vaccination regimen well, according to researchers. These results suggest that further development of the two-step immunotherapy regimen is promising for treatment of ovarian cancer.

“We are planning to take the dendritic vaccine into the primary setting with a clinical trial for patients who are in remission,” said Kandalaft.

Abstract LB-335

Nurse Perspective on Treating Ovarian Cancer

Emily Beard, RN, OCN, CBCNMultidisciplinary Care CoordinatorOncology Support ServicesNorthside Hospital Cancer InstituteAtlanta, GA

Though small and preliminary, the promise this study holds is significant. It is especially welcome news for clinicians weary from waging war against ovarian cancer, with little in the way of new hope to offer patients for treatment and cure, particularly those with recurrent disease. The typical ovarian cancer progression is, as Dr. Azvolinsky describes, challenging to diagnose and treat. Once a patient recurs on first-line systemic therapy, the list of evidence-based treatment options is limited. Therefore, the implications of this study and the role of immunotherapy in managing patients with advanced ovarian cancer is potentially game changing.

As exciting as the 61% of patients who showed a clinical benefit is the success of the science behind the vaccine and T-cell therapy process, with its ability to outwit tumor biology by mediating a cell response and beating cancer at its own game on the cellular level. I am anxious to see what results come with future studies, especially when the vaccine is administered to patients already in remission. Using the patient’s own immune system to mount an attack against malignant cells begs us to ask the question: Is this the dawn of a new era in oncology? Will we look back on this and other vaccine trials and recognize them as watersheds of the future in cancer treatment and cure?

To answer those questions, we should be urging all of our cancer patients to consider participating in all phases of clinical research, especially in studies of novel therapies. As oncology professionals, it is our charge to help patients and fellow clinicians understand the myriad benefits derived from participating in appropriate research, to identify barriers to that participation, and to create strategies to overcome them.

In this age of personalized medicine, perhaps we will deliver our patients the promise of long-term disease-free survival and hope for a long-sought-after cure!

Melanoma

Melanoma Survivors Need Better Education About Sun Protection

According to the results of a large study announced at the Annual Meeting of the American Association for Cancer Research, a sizeable proportion of patients with melanoma self-report suboptimal skin-protection practices, including not using sunscreen when outdoors.

The survey focused on questions to melanoma survivors about sun protection practices and indoor tanning, and found that >25% reported no sunscreen use when outside for more than 1 hour, and slightly more than 2% still use tanning beds. (Table) These data suggest that better patient education is needed for patients who develop melanoma, said the authors.

“Melanoma is a prevalent malignancy in the United States, and sun exposure is a major risk factor for recurrence. Sun protection may reduce the risk of recurrent melanoma. Although our study found that melanoma survivors did better than the general public at protecting their skin from sun exposure, we also found that more than a quarter of melanoma survivors never wear sunscreen. That blew my mind!” stated senior author Anees B. Chagpar, MD, associate professor of Surgery at Yale School of Medicine in New Haven, Connecticut.

The study was based on data from the 2010 National Health Interview Survey, an annual, crosssectional survey of noninstutionalized adults in the United States that includes questions on a wide range of health topics. Of 27,120 adults, 171 reported a prior history of melanoma.

Table. Sun Protection Behaviors

Melanoma Survivors

Persons Without Melanoma

Seeks shade when outdoors

15.6%

10.5%

Wear cap/visor outdoors

31.3%

18.4%

Wear wide-brimmed hat outdoors

20.5%

6.1%

Wear long-sleeved shirt outdoors

12%

5.2%

Use sunscreen outdoors

32%

17.2%

Gardener: Alexander Raths - Fotolia.com Umbrella: flucas - Fotolia.com

The good news is that survivors were more likely than people without a melanoma history to seek protection in the shade, wear a baseball cap/visor, wide-brimmed hat, and/or a long-sleeved shirt when outside on a warm sunny day for more than an hour. They were also more likely to follow the recommendation for wearing sunscreen outdoors than people who had no history of melanoma.

Disappointingly, 15.4% of melanoma survivors said they rarely or never sought shade coverage outdoors, 27.3% reported no sunscreen use when outdoors on a sunny day for more than 1 hour, and 2.1% reported tanning bed use within the previous year.

Even after controlling for the fact that most melanoma survivors in the survey were non-Hispanic whites and were covered by Medicare, melanoma survivors were not less likely to use a tanning bed than the general population without a melanoma diagnosis, and not more likely than the general population to use sunscreen.

Chagpar called the data “concerning,” and said that melanoma survivors should be educated about the need for sun protection behaviors and avoidance of indoor tanning beds. Abstract 1365

Nurse Perspective on Sun Protection

Colleen M. O'Leary, RN, MSN, AOCNSOtolaryngology Clinical Nurse SpecialistThe James Cancer HospitalThe Ohio State University Medical Center, Columbus

When reading the results of this study, I would think that most people would agree with Dr. Chagpar’s comments regarding how incredulous this thought is. After all, one would think that if a person has survived the cancer journey, he or she would do anything to not experience that again. With the incidence of cutaneous malignant melanoma (CMM) having increased 690% from 1950 to 2001,1 perhaps we need to ask what is the difference with this group? And, maybe even more importantly, what can we, as healthcare providers, do better to ensure that we play a strong role in prevention of further cancers?

First, we have to understand the science behind the protective interventions that we are upholding. We know that both UVA and UVB radiation are emitted from the sun. Originally it was thought that UVB radiation was the primary culprit in cancer formation because of the direct damage to DNA by UVB rays. Because of this, most sunscreens were developed to block UVB rays with little effect on UVA radiation. The sun protection factor that we see on topical sunscreens relates to only UVB protection. However, more recent studies have shown that UVA rays may also play a part in the initiation of CMM. The damage by UVA rays is not direct DNA damage but is due to effects of oxidative stress, free radicals, and degradation of vitamin D.2 Since sunlamps and tanning beds give off a higher ratio of UVA to UVB than natural sunlight, this may be the reason that they possess an increased risk of CMM.

Anything that temporarily blocks UV radiation can be considered a “sunscreen,” including lotions, creams, protective clothing, umbrellas, sunglasses, and hats. There are two types of topical sunscreen; organic and inorganic UV filters. Organic filters absorb UV radiation while inorganic filters scatter and deflect UV radiation.3 Inorganic filters such as those in zinc oxide and titanium dioxide do not break down as easily over time and are generally well tolerated. The downside is that they don’t blend in well and are evident on the skin. Organic UV filters come in the form of creams and lotions. They tend to degrade over time, and thus must be reapplied often. They may also cause a variety of skin reactions including a variety of types of dermatitis.

And, what about that sun protection factor (SPF)? What should we be recommending? The SPF measures the ratio of time it takes to sunburn with protection divided by the time it takes to burn without protection with an application of 2 mg/cm. Although that information may not be so useful, the bottom line is that the higher the SPF, the more protection. For instance, SPF of 15 filters 94% of UVB while an SPF of 30 filters 97%. SPF above 30 shows only marginal increases in protection.3 However, a 2010 study looking at the comparison between SPF of 50 with SPF of 85 to see if there was actual increased protection,4 showed that there was a higher level of protection. The issue with all of the sunscreen studies is that they are done in controlled environments with optimum amount of sunscreen applied in appropriate timeframes. In reality, people tend to underapply sunscreens with the resulting SPF only being 20% -50% of the labeled SPF. Therefore, using a higher level of SPF may get the desired results.

Finally, there have been other studies that support the assertion of this report with some additional information showing that recently diagnosed and treated patients received onethird the amount of UV exposure than matched controls and sunscreen was used twice as much.5 However, with patients who were diagnosed >12 months earlier, the UVR dose was one-third higher, and the number of days using sunscreen was half that of the recently diagnosed patients.5

These results demonstrate that in order to more effectively educate patients about their protection, we need to start with educating ourselves. We need to be familiar with the primary sources of UVA and UVB radiation and the results of exposure, the different protective mechanisms available and how they work, and the need to reinforce the importance of protective education more often and periodically throughout years of follow-up.

References

  • De Giorgi V, Gori A, Grazzini M, et al. Epidemiology of melanoma: is it still epidemic? What is the role of the sun, sunbeds, Vit D, betablocks, and others? Dermatol Ther. 2012;(25)5:392-396.
  • Planta MB. Sunscreen and melanoma: is our prevention message correct? J Am Board Fam Med. 2011;24(6):735-739.
  • Mulliken JS, Russak JE, Rigel DS. The effect of sunscreen on melanoma risk. Dermatol Clin. 2012;30(3):369-376.
  • Russak JE, Chen T, Appa Y, Rigel D. A comparison of sunburn protection of high-sun protection factor (SPF) sunscreens: SPF 85 sunscreen is significantly more protective than SPF 50. J Am Acad Dermatol. 62(2):348-349.
  • Idorn LW, Datta P, Heydenreich J, Philipsen PA, Wulf HC. Sun behavior after cutaneous malignant melanoma: a sudy based on untraviolet radiation measurements and sun diary data. B J Dermatol. 168(2):367-373.

Preliminary Evidence Suggests That Intermittent Dosing Can Overcome Resistance to Vemurafenib

The availability of vemurafenib was considered a major advance in the treatment of melanoma. Although patients with BRAF mutations initially respond to treatment with vemurafenib, resistance to the drug eventually develops. A preliminary study presented at the recent Annual Meeting of American Association for Cancer Research suggests that using an intermittent dosing strategy with vemurafenib instead of continuous dosing has the potential to overcome the development of resistance in patients with melanoma treated with the drug.

“When vemurafenib was introduced, it was exciting to witness the translation of the discovery of BRAF mutations in melanoma into an effective therapy. However, it was disappointing to see patients stop responding to such a promising therapy after 6 to 8 months of treatment,” said Darrin Stuart, PhD, senior research investigator at the Novartis Institutes for Biomedical Research in Emeryville, California.

BRAF mutations occur in >50% of melanoma patients, and vemurafenib extends survival for these patients. However, most of these patients will relapse with lethal drug-resistant disease, Stuart emphasized.

A previous study by Stuart and colleagues (Nature. 2013;494(7436):251-255) found that xenografts of melanoma tumors expressing BRAF mutations that were implanted in experimental mouse models developed resistance to vemurafenib; moreover, the tumors exhibited dependence on vemurafenib to sustain their growth. When the drug was stopped, tumor growth was suspended, and some tumors regressed in the mouse model.

Stuart and colleagues sought to determine whether the drug dependency of the tumors observed in experimental animal models was also present in humans. They studied 42 patients with vemurafenib-resistant tumors. CT scans were available for 19 of these patients who were taken off treatment; 14 of the 19 demonstrated a decrease in the rate of tumor growth once they were no longer taking vemurafenib.

“This is the first evidence that the drug-addicted state that we observed in mouse models may also occur in humans,” he stated.

The next step was to implant xenografts of patientderived BRAF-positive tumors in mice and treat them with vemurafenib either on an intermittent schedule of 4 weeks on/4 weeks off, or on continuous treatment. None of the animals in the intermittent dosing group developed drug resistance.

Continuous dosing maintained the selective pressure required for the few surviving tumor cells to develop resistance, and alternating the selective pressure through intermittent dosing appeared to prevent the evolution and expansion of resistant cells, Stuart said. “Patients derive a clinical benefit from vemurafenib and then develop resistance. Some sort of drug holiday makes sense. I hope people will study this clinically.” Abstract LB-144.

Survivorship Care

Meeting the Psychosocial Care Needs of Cancer Survivors

By Lauren M. Green

Less than one-third of all survivors of adult cancers in the United States had discussions with their healthcare providers about their psychosocial care needs, according to a new study published online ahead of print April 22, 2013 in the Journal of Clinical Oncology (doi: 10.1200/JCO.2012.46.2101).

This population-based study of 1777 survivors participating in the 2010 National Health Interview Survey (NHIS) was conducted by researchers at the National Cancer Institute, the Patient-Centered Outcomes Research Institute (PCORI), the Centers for Disease Control and Prevention (CDC), and Wake Forest University School of Medicine.

The study examines the level of psychosocial care being provided in clinical practice, following on the 2008 Institute of Medicine (IOM) report, Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs. In this report, the IOM called for better identification of patients’ psychosocial needs, more effective provider—patient communication concerning those needs, and the implementation of coordinated care plans to link psychosocial services to patients who need them.

The NHIS was an in-person, national survey conducted by the National Center for Health Statistics and the CDC. Trained census workers conducted the computer-assisted personal interviews. Most of the survivors interviewed (61.2%) were aged ≥50 years; cancers of the breast (20.1%), prostate (15.5%), and melanoma (10.1%) were the most prevalent experienced by those responding to the survey.

Overall, 55.1% of the respondents said that they did not discuss their psychosocial care needs with a healthcare provider, nor did they use professional counseling or support groups (PCSGs); 31.4% reported having only a provider discussion, 4.4% reported accessing only PCSG, and 8.9% reported having both a provider discussion and PCSG. The researchers extrapolated the finding that only 40.2% of survivors had a provider discussion with or without PCSG, to estimate that approximately 7.5 million cancer survivors in the US did not discuss their psychosocial functioning with a healthcare provider.

Despite these findings, the researchers reported that the majority of survivors interviewed (74.9%) expressed satisfaction with how their psychosocial needs were met; those who had provider discussion, PCSG, or both, however, were more likely to be “very satisfied” than those who did not engage in such discussions or support services.

Within the more prevalent cancer site subgroups participating in the survey, breast cancer survivors were more likely both to report a discussion of their psychosocial needs with a provider and PCSG use. Notably, unmarried survivors, who often are more in need of psychosocial support, were less likely to report provider discussions.

A possible limitation of the study, the researchers noted, is that recall bias in self-reported data may result in respondents underreporting their engagement in PCSG or having had provider discussions.

Laura P. Forsythe, PhD, MPH, a program officer at the PCORI, and colleagues noted that to the best of their knowledge that this study is the first “to provide population-based data regarding healthcare provider discussions with survivors about psychosocial concerns after cancer.”

In an accompanying editorial (J Clin Oncol. 2013; doi: 10.1200/JCO.2012.48.0566), William F. Pirl, MD, director of the Center for Psychiatric Oncology and Behavioral Sciences at Massachusetts General Hospital in Boston, and colleagues wrote: “Taken together, these findings provide the most compelling evidence to date that heightened psychological distress in many patients with cancer is still unrecognized and untreated.”

“If we are proactive, we can use these data to create successful systems in which all cancer survivors will have some discussion with their providers about psychosocial care, whether or not they choose to use psychosocial services.”

Nurse Perspective on Psychosocial Care

Donna Meyer, BSN, MSSurvivorship CoordinatorNorthside Hospital Cancer InstituteAtlanta, GA

The results of this study indicate that two-thirds of cancer survivors did not have a conversation with their healthcare provider concerning their psychosocial care needs. If the conversation is not taking place, the Institute of Medicine goals of better identification of patients’ psychosocial needs, increased communication, and linking patients with services cannot be attained.

Survivors were also asked to rate their level of satisfaction with how their psychosocial needs were met. Over two-thirds of the respondents indicated that they were “satisfied.” Patients who had higher levels of conversation by combining counseling, support groups, and provider discussion were more likely to be “very satisfied” with their care.

These statistics are interesting in that the literature describes the number of cancer patients who typically report significant levels of distress (≥4-5 on the National Comprehensive Cancer Network [NCCN] Distress Thermometer) ranges between 22%-58%. The average level of distress using these figures is 40%. These patients are distressed because their cancer diagnosis/treatment has overcome their ability to cope using their usual resources. The 74.9% of satisfied patients may represent those who have adequate support resources to adapt to their circumstances. Those who have inadequate resources or previous psychological disorders are probably not receiving the support that they need and are not saying that they are satisfied.

The Commission on Cancer Standard 3.2 mandates the incorporation of psychosocial distress screening as part of the standard care of oncology patients. By implementing distress screening, using validated tools, the care providers will be given a routine assessment framework and will develop referral pathways to utilize local and national resources. Patients will be given the opportunity to voice their needs, communication will be improved, and distressed patients with inadequate resources will receive support.

Repeating this study after broad implementation of distress screening will likely yield a very different result.

Reducing the Burden of Bone Metastases and Skeletal-Related Events

By Lauren M. Green

Bone metastases and skeletal-related events (SREs) are often the first metastatic sites in breast and prostate cancer, and also can occur secondary to other solid tumors, negatively impacting quality of life for patients and posing a significant economic burden, US data show. Similar trends are now being seen in Europe, and a group of researchers there—reporting in the June issue of Supportive Care in Caner (2013;21(6):1773-1783)—conducted a comprehensive literature review to provide a clearer picture of current treatment approaches for these events aimed at reducing their personal, social, and financial burden.

For their review, the authors searched the PubMed database from 2000 to the present, as well as findings reported since 2009 at major professional meetings, including the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology.

The investigators found that impact of bone metastases and SREs in cancer care is large. Their review of 10 historical studies, separate from their larger search of more recent data from PubMed and professional meetings, found that skeletal metastases were present in approximately 70% of patients with metastatic prostate or breast cancer at autopsy, and in about 40% of patients with metastatic lung cancer. SREs are experienced by most patients who develop bone metastases; these events include spinal cord compression, bone instability or fractures requiring surgery, and radiotherapy for bone pain or impending fracture.

The pain associated with these events can significantly reduce quality of life for patients—limiting their daily activity and independence—and treatment often requires analgesia with opioids, which do not address the underlying cause of the pain and can result in side effects, such as nausea, decreased alertness, constipation, and, in some cases, addiction. When pain worsens, some patients will become depressed, believing their bone pain to be a sign that their disease has progressed.

In addition to their personal and emotional toll, cancer-related bone disorders also are “a significant driver of overall oncology expenditure” in the US, and similar economic burdens are now being seen in Europe, study authors noted.

Selecting the appropriate bone-modifying agent by carefully weighing risks is critical to reducing bone-related morbidity. Currently, the various bone-targeted treatment options for these events center on preventing or delaying SREs, repairing or stabilizing bone, and pain palliation. Among these options are radiotherapy and surgery to the bone, as well as the use radiopharmaceuticals, including the new agent radium-223 dichloride (Xofigo), which was approved by the FDA last month for the treatment of symptomatic metastatic castration-resistant prostate cancer that has spread to the bones but not to any other organs.

Bisphosphonates also have shown effectiveness in reducing the occurrence and delaying the onset of SREs, preventing increase in pain, and improving quality of life. Use of these agents has proven to be cost-effective when compared with no treatment, and research has shown zoledronic acid, the most widely used bisphosphonate, to be more cost-effective than other bisphosphonates. The authors did note that despite these positive effects, the agents are associated with several adverse events (eg, renal toxicity, acute-phase reactions) and hypocalcemia. Researchers are looking at optimal dosing regimens, such as the most suitable time to initiate treatment and the benefits and risks of long-term therapy.

Recent studies have reported that the monoclonal antibody denosumab has been shown to be superior to zoledronic acid in delaying and preventing SREs in patients with breast cancer and prostate cancer, and that the drug also has shown potential in preventing metastases—an unmet clinical need. Its safety and tolerability profile is comparable to that of bisphosphonates, including risk of hypocalcemia, but denosumab is not associated with renal toxicity, and fewer acute-phase reactions have been reported. A recent study of the therapy’s cost-effectiveness in Sweden, Switzerland, and Portugal reported per-patient cost savings favoring denosumab versus zoledronic acid in breast and prostate cancer, with savings driven by fewer SREs, higher quality-of-life years, and lower overall costs.

The authors also noted the recent emergence of experimental agents targeting both the primary tumor and bone lesions, such as dasatinib and cabozantinib.

“Collectively, we are now in a position to begin the reshaping of evidence-based guidelines on the use of bone-targeted agents,” concluded Roger von Moos, MD, head of Medical Oncology/Haematology at Kantonsspital Graubünden in Switzerland, and colleagues. “In turn, this may help to improve patient care and reduce the economic burden associated with bone metastases.”

Home Medication Errors Common in Pediatric Cancer

As the number of oral cancer therapies increases, medications previously managed by nurses are now being administered by patients and their caregivers. Findings of a multisite study of medication administration in the home for children with cancer showed that errors were common in this setting, and most often involved nonchemotherapy drugs. (Pediatrics. 2013;131(5):E1405-E1414)

For this prospective, observational study at three pediatric oncology clinics, the researchers reviewed 963 medications, and trained research nurses observed 242 medication administrations during visits to the homes of 92 pediatric cancer patients. Seventy-eight percent of pediatric patients visited had leukemia. The median number of medications taken at home was 10 (range: 3-26). Parents were for the most part well-educated, with 97% scoring in the “adequate” range on a health literacy scale.

Any over-the-counter drug, prescription drug, or herbal supplement was considered to be a medication for the purposes of this study. A medication error was defined as a mistake in drug ordering, dispensing, administering, or monitoring. The determination as to whether an error occurred and its level of severity was based on independent review by two physicians.

Researchers found 72 medication errors; four resulted in injury and 40 had the potential for injury. The weighted overall rate was 70.2 errors per 100 patients; the weighted overall rate of errors with injury was 3.6 per 100 patients. Drug administration was responsible for 63.5% of errors, which study authors noted was sometimes due to a parent failing to make dose adjustments as instructed by the oncologist or the parent failing to communicate dose changes to other caregivers at home. Several errors involved parents selecting the wrong dose for acetaminophen. Notably, stated the authors, of 47 parents observed administering chemotherapy, only five wore gloves when handling these agents.

Physician reviewers indicated that better communication between families and physicians about medication use could have prevented 36% of errors.

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