Clinical Insights: October, 2012

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-oct-2012
  • Complete and submit the CE posttest and activity evaluation.
  • Print your Certificate of Credit.

This activity is provided free of charge to participants.

Breast Cancer

Study Supports Role for ALND in Early Breast Cancer

By Andrew Roth

Patients with early-stage breast cancer at high risk of residual nodal disease might benefit from axillary lymph node dissection (ALND), according to a simulation study1 that challenges certain findings of the controversial ACOSOG Z0011 trial.2

The study results, presented at the 2012 Breast Cancer Symposium held September 13-15 in San Francisco, suggest that ALND offers an improvement in long-term overall survival (OS) and quality of life for a segment of women weighing therapeutic options after undergoing breast-conserving surgery.

Researchers from Harvard Radiation Oncology set out to examine whether a subgroup of highrisk patients “were not adequately represented” in ACOSOG Z0011, lead investigator Monica Shalini Krishnan, MD, said at a press conference during the symposium. She is a resident in the Harvard Radiation Oncology residency program at Harvard University-affiliated hospitals in Boston.

Historically, patients with early-stage breast cancer who undergo breast-conserving surgery and have a positive sentinel lymph node biopsy have then received a completion ALND, Krishnan said. She noted that the Z0011 findings disputed that protocol. The Z0011 trial concluded that ALND did not significantly affect OS among patients who had limited sentinel lymph node metastases after breast-conserving surgery and systemic therapy.

In their simulation, the Harvard researchers applied algorithms to trial data to approximate results for hypothetical women aged 45, 55, and 75 with stage II breast cancer following breastconserving surgery with positive sentinel lymph nodes. They then were treated with either ALND and whole-breast radiation (BRT) or BRT alone.

The study simulated patients’ axillary recurrence risk, lymphedema, and quality-adjusted life expectancy (QALE). The patients were stratified into two risk groups: “high risk” patients were those with a 30%-60% risk of residual nodal involvement, while “low risk” patients had a <30% risk.

Patients in the high-risk group achieved a 20-year OS of 42% with ALND plus BRT, compared with 38% for BRT alone. The QALE was 14.36 years with ALND plus BRT, versus 13.55 years for BRT alone.

For the low-risk group, there was virtually no difference with ALND. The 20-year OS was 47% with and without ALND, and the QALE was 15.46 years with ALDN and 15.53 without it.

Krishnan said the hypothetical patients in her study would have been eligible for inclusion in ACOSOG Z0011, and therefore would be valuable in deciding upon therapeutic options.

“While it is not a substitute for clinical data, this simulation can at least inform what options physicians discuss with their patients and give physicians a basis for considering axillary lymph node surgery in patients with high risk of residual nodal disease,” Krishnan said.

References

  • Krishnan MS, Recht A, Bellon JR, et al. Trade-offs associated with axillary lymph node dissection: implications of the eligibility versus enrollment in ACOSOG Z0011. J Clin Oncol. 2012;30(suppl 27; abstr 151).
  • Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection versus no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011;305(6):569-575.

Decision Styles Affect Chemotherapy Use in Older Patients

By Jill Stein

Older women with breast cancer who prefer less input from their physician when deciding on treatment are less likely to receive chemotherapy than women who prefer to rely on their physician to a greater degree, a recent study has found (J Clin Oncol. 2012;30(21):2609-2614).

The data also show that patients whose oncologist had a higher preference for chemotherapy had a greater likelihood of receiving chemotherapy than patients whose oncologist had a low preference.

Jeanne S. Mandelblatt, MD, associate director for population sciences at the Lombardi Comprehensive Cancer Center in Washington, DC, and coworkers elsewhere, examined associations between patient and oncologist decision-making styles and chemotherapy use.

For their study, the investigators used data from women 65 years of age or older who were newly diagnosed with invasive nonmetastatic breast cancer (tumors ≥1 cm) from January 2004 through April 2011 at 75 hospitals or practices affiliated with the Cancer and Leukemia Group B (CALGB) cooperative group.

About half of new cases of breast cancer in the United States and nearly two-thirds of breast cancer deaths occur in women 65 years of age or older, the authors observe. Decision-making about adjuvant chemotherapy in this cohort is complicated because there is scant evidence about its benefits. Also, older patients have multiple comorbidities, and there are concerns about treatment toxicity.

Oncologists treating study participants were mailed a brief survey that focused on their background and practice styles. Information on patients’ tumor characteristics and treatment history were obtained from medical records.

Patients’ decision style was measured on a 5-point scale. Oncologists’ preference for prescribing chemotherapy was based on responses to 4 hypothetical case scenarios.

The analysis included 1174 women seen by 212 oncologists. Forty-three percent of women received chemotherapy.

Results showed that 30% of women preferred to make their chemotherapy decisions alone or mainly alone with some input from their physician. Forty-one percent said they favored joint decision-making.

Women who preferred to make their decisions with less input from their physician were significantly less likely to have had chemotherapy than women who had a preference for more input (the odds of chemotherapy decreased by 21% for each 1-point change on the decision-making scale (95% CI, 0.65-0.97; P = .02), adjusting for covariates.

The odds of receiving chemotherapy among women whose oncologist had a high preference for recommending chemotherapy were 2.65 times higher (95% CI, 1.80-3.89; P < .001) than the odds of receiving chemotherapy among women who were seen by oncologists with a low preference.

Nurse Perspective on Decision Styles

Peg Farrar, MS, RNInstructor, Carrington CollegeReno, NV

According to the 2010 Census, there are more people over 65 than in the US than ever before, so it is appropriate that researchers examine this population for its decision-making regarding cancer treatment. This article summarizes a recent study that did just that, and found that the older adult population is as varied as any other. There were many who chose to make decisions themselves, rather than rely solely on their physicians for advice.

The study raises several questions:

How well did the women know the oncologist prior to the decision-making? Most, if not all, patients only see an oncologist after a cancer diagnosis. They do not know that oncologist well, and may choose to discuss their decisions with their primary healthcare provider with whom they have a longer relationship. In addition, family involvement is often crucial to older adults in their decision-making.

Has the increasing involvement of nurse navigators (NNs) changed the decision-making of older women with breast cancer? This study was done between 2004 and 2011, prior to the advent of widespread nurse navigators. As a former NN, I know that the discussions held with patients and families are in-depth, and a great deal of information is disseminated that can help with treatment decisions. Because of the NN involvement from the moment of initial diagnosis, there is a level of familiarity and trust there that has been established long before the patient sees the oncologist.

Was cost a factor for any of the women who chose not to have chemotherapy? In my experience, despite Medicare coverage, there are many costs associated with treatment that add up for many older patients. Both deductibles and copays can be expensive, as well as “hidden” costs associated with treatment, such as travel costs and time off work. (Yes, many seniors are still working!) In my case, over 25% of the women with breast cancer lived >20 miles from the cancer center, and some >200 miles away. Some chose to forego chemotherapy because of the costs associated with hotels, gas, etc. (We established a gas card program to assist with these expenses—an example of the work of nurse navigators!)

And finally, have we been able to resolve some of the variables discussed in the study, such as the empirical evidence about risks and benefits of treatment? The fact that we have been successful in treating early-stage breast cancer is wonderful, but long-term follow-up of these women takes many years. So it makes sense that we will not have data for awhile comparing the groups of women who chose to receive chemotherapy and the women who chose not to. Even then, we will have to tease out the comorbidity issues to arrive at a better risk/benefit analysis.

I look forward to more studies on older adults with cancer—they are a wonderful group of patients who want to have a high quality of life. As we offer more treatment choices, we need to make certain that we give them as much information as possible to make an informed decision.

Supportive Care

L-Carnitine Does Not Reduce

Cancer Fatigue, Study Finds

By Jill Stein

L-carnitine does not reduce fatigue in cancer patients, according to the results of the largest clinical study to date to test the effect of the popular supplement in patients with invasive malignancy and fatigue (J Clin Oncol. 2012. doi:10.1200/JCO.2011.40.2180).

The data, from a phase III study, showed that 1 g twice daily of oral L-carnitine supplementation for 4 weeks did not improve fatigue on the widely validated Brief Fatigue Inventory (BFI).

Ricardo A. Cruciani, MD, PhD, vice chairman and chief of the Pain Division at Beth Israel Medical Center in New York City, and associates caution, however, that their study has “important limitations.” For example, 25% to 30% of patients did not complete evaluations, and it was not known whether those individuals had an improvement in fatigue or actually worsened. The investigators were quick to emphasize, however, that the proportion of missing follow-up evaluations is typical of that seen in prior studies that have symptoms as primary outcomes.

Overall, 376 patients with an invasive malignant disorder and moderate to severe fatigue were randomized to either 2 g per day of L-carnitine or placebo. Study participants were drawn from 24 Eastern Cooperative Oncology Group (ECOG) sites. About one-third of patients in both treatment groups had carnitine deficiency at baseline.

Adults and children with chronic diseases are at increased risk of carnitine deficiency because of decreased intake and increased utilization or elimination, the authors point out. Open-label studies in adults found that L-carnitine supplementation may lesson fatigue in cancer patients who are carnitine-deficient due to chemotherapy, and may also improve sleep and depressed mood.

The primary endpoint in the present study was the difference between arms in change in BFI from baseline to week 4.

The data showed that BFI-measured fatigue improved in both study groups compared with baseline (L-carnitine: -0.96; 95% CI, -1.32 to -0.60; placebo: -1.11; 95% CI, -1.44 to -0.78), with no statistically significant differences between groups (P = .57).

There were no significant differences between treatment groups on secondary endpoints, including fatigue measured by the Functional Assessment of Chronic Illness Therapy-Fatigue scale.

When analyzed separately, patients who were carnitine-deficient at baseline had no statistically significant improvement in fatigue or other outcomes after L-carnitine supplementation.

Cruciani et al said that the results may be weakened by the fact that the dose and duration of L-carnitine supplementation and patient population included in the study differ from those of some other investigations that have reported favorable results.

In addition, depression and pain commonly occur in patients with advanced cancer and “could confound the fatigue analysis.”

Nurse Perspective on L-carnitine

Janice Famorca Tran, RN, MS, AOCNP®, CBCN®, ANP-CTexas OncologyHouston, TX

L-carnitine is a naturally occurring amino acid that plays a vital role in the metabolism of fat. It functions to transport fatty acids into the mitochondria, facilitating their oxidation with subsequent energy production. In the US, carnitine is an approved prescription drug for the treatment of systemic carnitine deficiency.

Cancer-related fatigue (CRF) is one of the most common symptoms reported by patients. CRF is defined as a feeling of exhaustion associated with high levels of distress, not relieved by sleep or rest. The prevalence of this problem among cancer patients ranges from 59% to 100%, depending on the clinical course of the cancer. CRF can have a profound impact on the quality of life of the individual.

The study performed by Cruciani et al examined the effects of L-carnitine on the level of fatigue in patients with invasive cancer. Patients were diagnosed as having either moderate or severe fatigue. Both the treatment and control arms revealed an improvement in the level of fatigue compared to baseline; however, there was no statistical difference between the groups. The study further revealed that L-carnitine supplementation did not improve fatigue in those who were carnitine-deficient at baseline nor did it improve depression or pain.

True accurate results may have been weakened as a result of 25% to 30% of the participants’ failure to complete the evaluations. The results also revealed the possibility of a “placebo” effect. Consideration of underlying causes of CRF is a significant factor in assessing levels of fatigue. These factors include anemia, combination therapy, decreased nutritional state, hypothyroidism, pain, stress, insomnia, and other medications. Often, the feeling of depression is accompanied by fatigue. The most effective way to combat fatigue in those with cancer is to treat the underlying cause. If the cause is unknown, strategies such as energy conservation, promotion of physical activity, stress reduction, and adequate nutrition should be implemented, as these strategies have been proven to be effective in reducing CRF.

Pain in Oncology Outpatients with Solid Tumors Remains Undertreated

By Jill Stein

Pain is as common in ambulatory oncology patients with common solid tumors as it was nearly two decades ago, despite the dramatic increase in opioid prescriptions, new data suggest (J Clin Oncol. 2012;30(16):1980-1988).

The results, which are from the largest prospective assessment of pain and other symptoms in ambulatory oncology in the US, also bolster prior reports of a higher probability of inadequate pain management in minority patients than in non-Hispanic whites.

Michael J. Fisch, MD, chairman of the department of General Oncology at the University of Texas MD Anderson Cancer Center in Houston, and associates elsewhere, determined the prevalence of pain and analgesic use in 3123 ambulatory patients with invasive cancer of the breast, prostate, colon/rectum, or lung. Patients were eligible for enrollment irrespective of their phase of care or disease stage.

Of 3023 who were identified as being at risk for pain during their initial assessment, 2026 (67%) reported having pain or receiving analgesic treatment. Of the 2026 patients, 670 (33%) had inadequate treatment of their pain.

The results were nearly the same at baseline assessment as they were at a follow-up assessment 4 to 5 weeks later.

After controlling for other explanatory variables, the odds of a non-Hispanic white patient having inadequate pain treatment both at the initial assessment and follow-up were about half those of a minority patient (OR, 0.51; 95% CI, 0.37 - 0.70; P = .002).

Patients were also significantly more likely to have inadequate pain management if they had a good performance status, were treated at a minority treatment site, and had nonadvanced disease without concurrent treatment.

Fisch et al note that his group’s findings parallel those reported in a landmark study by the Eastern Cooperative Oncology Group (ECOG) in 1994, which found that two-thirds of medical oncology outpatients with advanced cancer required or used analgesics and that analgesic, prescribing was inadequate in about 40% of these patients. Notably, since the ECOG study, opioid prescribing in the United States has risen more than 10-fold.

The authors acknowledge that while their findings can be extrapolated to patients with common solid tumors who are cared for at facilities that are associated with a US clinical cooperative group, many ambulatory patients with cancer have less common solid tumors or hematologic malignancies and/or are cared for elsewhere besides the cooperative system.

In addition, they did not obtain information that might have affected pain management practice, such as patient comorbidities, insurance status, socioeconomic status, or clinician characteristics like age, race, and gender.

Nurse Perspective on Cancer Pain

David Leos, RN, MBA, OCN®Clinical Trials NurseMD Anderson Cancer CenterHouston, Texas

Pain unfortunately still figures heavily in the cancer experience. After years in oncology practice, I, too, make this association, albeit one that has lessened somewhat with advances in therapy, and the perceived notion that these therapies are being broadly applied and barriers are being overcome to the benefit of those who suffer.

This article underscores the unfortunate lack of real progress in pain control, a problem brought to the forefront by ECOG. While these shortcomings in the patient population as a whole are sad to say the least, particularly distressing is the finding of a persistent disparity within minority populations, as if the prospects of poorer treatment outcomes in this population were not bad enough. Personal experience and literature results point to economic, cultural (stoicism), and educational differences as probable sources for these study findings.

Stockler and Wilcken (J Clin Oncol. 2012;30(16):1907-1908) note that the most significant barriers to pain management have changed little in 20 years and include poor assessment by healthcare providers, patient reluctance to take opioids, and patient reluctance to report pain. They also point out the infrequency of referral to a pain specialist or to palliative care.

According to a statement from the International Association for the Study of Pain, Barriers to Cancer Pain Treatment (2009), the other stakeholder in this barrier triad is a healthcare system that contends with a strict regulatory environment that influences prescribing practices and has not moved fast enough in instituting better pain management curricula for healthcare professionals—this, in spite of Joint Commission pain management standards (2001) for ambulatory care and other healthcare organizations that recognize this as a patient right.

Lung Cancer

Addition of Motesanib to Chemotherapy No Significant

Benefit in NSCLC

By Jill Stein

Motesanib combined with carboplatin/ paclitaxel does not significantly improve overall survival (OS) over carboplatin/pacliaxel alone in patients with advanced nonsquamous non—small cell lung cancer (NSCLC), according to the results of the phase III Motesanib NSCLC Efficacy and Tolerability (MONET1) study (J Clin Oncol. 2012;30(23):2829-2836).

The data also showed that the agent did not prolong OS in a subset of patients with adenocarcinoma histology.

Giorgio V. Scagliotti, MD, professor of Medicine at the University of Turin, Italy, and colleagues elsewhere, randomized 1090 patients to carboplatin (area under the curve, 6 mg/mL/min) and paclitaxel (200 mg/m2) intravenously for up to six 3-week cycles plus once-daily oral motesanib 125 mg or placebo.

Study participants had stage IIIB/IV or recurrent nonsquamous NSCLC and had not undergone systemic therapy for advanced disease. The study’s primary endpoint was OS.

Motesanib is an oral, small-molecule, targeted antagonist of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit. The agent has shown antitumor activity in NSCLC patients when administered alone or combined with chemotherapy.

The median OS in the motesanib group was 13.0 months versus 11.0 months for the placebo group (HR = 0.90; 95% CI, 0.78 - 1.04; P = .14). In the subset of 890 patients with adenocarcinoma, the median OS was 13.5 months with motesanib and 11.0 months with placebo (HR = 0.88; 95% CI, 0.75 - 1.03; P = .11).

In all patients with nonsquamous histology, the median progression-free survival (PFS) time was 5.6 months for motesanib and 5.4 months for placebo (P < .001). The overall response rates (ORRs) were 40% versus 26%, (P < .001). PFS and ORR were secondary study endpoints.

A prespecified ethnicity/regional subanalysis revealed that Asian patients, who comprised 25% of the enrolled study population, were the only subset of patients who had improved OS from motesanib.

Serious adverse effects occurred in 49% of patients in the motesanib arm versus 34% in the chemotherapy-only arm. Motesanib-treated patients had an increased incidence of diarrhea, nausea, vomiting, abdominal pain, hypertension, proteinuria, stomatitis, gallbladder disorders, neutropenia, and thrombocytopenia.

The investigators found no association between levels of placental growth factor (PLGF) and response rate or survival. PLGF, which is a VEGF homolog that can promote angiogenesis by activating VEGF receptor 1, had been shown to increase in response to motesanib in a prior phase II study.

Scagliotti et al say that their findings bolster mounting evidence suggesting that VEGF pathway inhibitors in tandem with chemotherapy do not offer significant benefit to unselected patients with nonsquamous NSCLC. More studies with these agents are not likely to be fruitful without improved patient selection using biomarkers.

Nurse Perspective on Motesanib

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

In previous studies, the use of targeted antiangiogenic agents showed great promise in the treatment of metastatic, nonsquamous, non-small cell lung cancer (NSCLC), laying the groundwork for further research on new investigational agents such as motesanib. Several studies, along with data that demonstrated motesanib having antitumor activity against five different human NSCLC xenograft models with diverse genetic mutations, led to the hope that motesanib would be effective in treating metastatic, nonsquamous NSCLC.

Unfortunately, the results of the MONET1 trial described above were less than expected. Along with no increase in overall survival (OS), several toxicities were observed in the patients receiving motesanib. Although both arms of the study showed about the same amount of grade 3 toxicities, the incidence of grade 4 and 5 adverse events (AEs) was significantly higher in the motesanib arm. Grade 4 neutropenia had the highest percentage of difference in this group, with 12% of patients reporting it. In addition, 31% of the patients receiving motesanib discontinued the drug related to AEs as compared with 15% in the placebo arm, and 14% of patients versus 9% in the placebo arm experienced fatal AEs within 30 days of the treatment.

Although the data are disappointing, a potentially promising result was also seen. A statistically significant improvement in OS, progression-free survival, and objective response rates was seen in a subset of Asian participants. This finding has prompted Takeda Pharmaceutical Company to initiate a phase III clinical trial in Japan, Hong Kong, South Korea, and Taiwan, evaluating motesanib in combination with chemotherapy in patients with advanced nonsquamous NSCLC.1

It is important for healthcare providers to understand the long and painstaking road to development of novel therapies. This is just one example of the twists and turns that researchers encounter when attempting to find the best treatment options. It is one more step towards defining the genetic subsets that may or may not be significant in one person’s treatment plan. We can no longer think of cancer treatment in broad terms, but are moving ever closer to defining true personalized medicine based on genetic qualities and outcomes.

Reference

1. Takeda Pharmaceutical Company Limited. Takeda initiates phase 3 trial of motesanib in Japan and additional Asian countries. Press release. http://www.takeda.com/press/article_47169.html. Accessed October 16, 2012.

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