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 hours. 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.
A program to help patients with breast cancer to create personal websites, so that they can write about their experiences and communicate more effectively with their social network, yielded statistically significant improvement in depressive symptoms, positive mood, and life appreciation among its participants, establishing a basis for a larger study of the intervention. (J Clin Oncol. 2013. doi: 10.1200/JCO.2012.46.9015)
To test their hypothesis that women trained in maintaining a personal website would reap psychological benefits from such engagement, researchers—led by Annette Stanton, PhD, professor in the Department of Psychology at UCLA and a member of the Division of Cancer Prevention and Control Research at the Jonsson Comprehensive Cancer Center in Los Angeles, California—designed Project Connect Online (PCO), which comprises a 3-hour, hands-on, small-group workshop guiding patients in the construction of a personal website, follow-up phone communication to facilitate use of the tool, and a take-home manual.
During their 3-hour session, participants each created their own websites, using a standard design template offering several functions, including a journal blog with functionality for photos, a “How You Can Help” page where participants could suggest actions for visitors to the website (eg, providing a meal or written notes), and instructions for visitors to post messages and subscribe to automatic updates.
To test the efficacy of this approach, researchers recruited participants from community-based medical oncology practices focusing on breast cancer. Enrollees (n = 88) were randomly assigned to receive PCO (n = 46) or a waiting-list control (n = 42). The average age of participants was 56, with their breast cancer diagnosis occurring, on average, >5 years previously.
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.
Both groups were assessed at baseline and 6 months later, using such standard measures of psychological status as the Center for Epidemiologic Studies Depression Scale, the Profile of Mood States, the Impact of Event-Intrusion subscale (a cancer-related outcome measure), and two subscales of the Posttraumatic Growth Inventory: Appreciation of Life and Relating to Others. The control group received standard medical care and was offered PCO after the 6-month assessment had been completed.
Baseline assessments did not differ significantly between the PCO group and controls, although the status of women in current medical treatment was somewhat worse, researchers noted.
At the 6-month assessment, researchers reported significant improvement in depressive symptoms, positive mood, and life appreciation among patients using PCO, noting that the magnitude of the effect size for all statistically significant effects was moderate to large. The PCO benefit was not significant, however, for measures of negative mood, perceived strengthened relationships, or intrusive thoughts.
Women in active medical treatment—most of whom had metastatic disease—reported more depressive symptoms at the 6-month mark (P = .04), and for this subgroup, the PCO intervention was especially beneficial (P = .009).
The researchers added that this preliminary trial was the first of its kind, with high potential for dissemination. Topics for further research include whether the greater benefit observed in patients currently being treated and/or those with advanced disease is reproducible, an analysis of any cultural variation in effects, and a comparison of this intervention with other online or personal approaches.
Project Connect Online (PCO), a program to help breast cancer patients create a personal website so they can write about their experiences and communicate with others, showed promising effects, including improvement in depressive symptoms, positive mood, and life appreciation. Interestingly, women with metastatic disease and/or those undergoing chemotherapy benefited the most from PCO. Clinically this is concordant, as patients who have the greatest disease burden or are undergoing active chemotherapy are among the patients who have the most need for support.
In rural Kansas where I practice, cancer patients are often isolated and don’t have easy access to services like support groups and other educational programs. The PCO intervention is ideal for cancer patients who suffer from isolation. I think we all would agree that cancer patients who stay socially connected and have a good support system do better both physically and emotionally.
A challenge I perceive with the PCO intervention is funding and long-term implementation and maintenance of such a project. Perhaps larger tests of PCO with larger samples of patients and positive findings would strengthen support for this program and help elicit other sources of funding to assure the success of PCO.
With the approval of sipuleucel-T for prostate cancer, the notion of utilizing vaccines in the fight against various tumors has garnered considerable interest. Yet HER2-targeted vaccines for breast cancer have been in development for several years. Now, clinical trials of these vaccines are starting to yield very promising data, although work still needs to be done to determine which patients will benefit the most from this type of therapy.
At the 12th International Congress on the Future of Breast Cancer, held July 18-20, Elizabeth A. Mittendorf, MD, PhD, an assistant professor in the department of Surgical Oncology in the division of Surgery at The University of Texas MD Anderson Cancer Center in Houston, discussed the development of these vaccines, where they stand, and the challenges that lie ahead in terms of determining how efficacious this new class of drugs might be.
While sipuleucel-T is a dendritic cell vaccine, the vaccines currently in development for breast cancer are peptide vaccines, which are proteinbased vaccines that incorporate one or more short or long amino acid sequences as tumor antigens, which are then combined with a vaccine adjuvant. Mittendorf said that a peptide vaccine will stimulate a peptide-specific immune response.
The peptide vaccine that has been investigated the most thoroughly at this point is E75, also known by its brand name Neuvax. E75 is a 9-amino acid peptide derived from the extracellular domain of HER2. “Our group has hypothesized that cancer vaccines, such as E75 vaccine, will be more effective in minimal disease or adjuvant setting,” Mittendorf said.
patients—which Mittendorf noted is the largest number of patients enrolled in an adjuvant vaccine trial to date—with histologically confirmed breast cancer who were nodepositive or high-risk node-negative and had any level of HER2 were randomized into either the vaccination group (n = 108) or the control group (n = 79).
The majority of patients (81%) did experience grade 1 maximal toxicity, usually involving redness at the injection site. The majority of patients (71%) also experienced grade 1 systemic toxicity, usually involving bone pain or flu-like symptoms. Overall, the vaccine was relatively well-tolerated.
When a primary analysis of clinical benefit was performed after 18 months of follow-up, the disease-free survival (DFS) rate at that time was 92.5% in the vaccinated population compared with 77.0% in the control population (P = .04). When patients were followed up after 60 months, the DFS rate in the vaccinated population (89.7%) was better than what was seen in the control population (80.3%), but the difference was not statistically significant (P = .08).
Mittendorf explained that the lack of statistical significance from that follow-up comes with numerous caveats, explaining that more work needs to be done as to whether the correct population is receiving the vaccine and whether they are receiving the proper dosage.
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!
Adverse events (AEs) associated with ipilimumab (Yervoy) for the treatment of metastatic melanoma are better understood after further analysis of clinical trial data that led to the FDA’s 2011 approval of the drug, including when those AEs are likely to manifest and the best methods of managing them. (Cancer. 2013;119(9):1675-1682)
The results of the analysis confirm that “careful follow-up and early intervention,” coupled with guidelines-based management of immune-related adverse events (irAEs), are vital components of treating patients with the immunotherapy agent.
Jeffrey S. Weber, MD, PhD, of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, and others set out to look at the pivotal clinical trial data once again to determine the patterns and development of these AEs.
Weber and colleagues used data from the phase III MDX010-20 trial, in which 676 previously treated patients with metastatic melanoma were randomized 3:1:1 to receive ipilimumab 3 mg/kg plus the glycoprotein 100 melanoma antigen vaccine (gp100), ipilimumab 3 mg/kg plus placebo, or the gp100 vaccine plus placebo.
In the entire clinical trial population, 14 deaths appear related to the study drugs, including seven deaths associated with irAEs. For ipilimumab monotherapy, the irAEs consisted of one case each of bowel perforation and liver failure. Among those treated with ipilimumab plus gp100, deaths related to irAEs included three patients with bowel perforation/inflammatory colitis, bowel perforation, or multiorgan failure/peritonitis; and one case each of colitis and septicemia, and Guillain-Barré syndrome.
The most frequently reported irAEs affected the skin and gastrointestinal (GI) tract, and most of the patients who died as a result of irAEs experienced GI events, notably colitis. However, Weber et al noted that, “There is no evidence that bowel involvement in patients with melanoma increases the likelihood that colitis, especially dose-limiting colitis, will occur after receiving ipilimumab.”
Instead, they noted that patients with metastatic melanoma are predisposed to experience worse outcomes if colitis occurs. “The key to handling ipilimumab-associated colitis is rapid and timely intervention mediated by a high level of communication between staff and patients,” they wrote.
The researchers found that grade 2-5 irAEs tended to develop during the induction phase of treatment, which occurs between weeks 0 and 12 of treatment. Most of these irAEs, including those that were grade 3 or 4, were reversible, with grade 2 side effects generally being resolved in 6 weeks after induction and 8 weeks for grade 3 and 4 side effects.
“The severe side effects resolve quickly, meaning the patients aren’t sick for weeks and weeks and weeks, but the technically appropriate assessment of resolution can take a fair amount of time,” Weber said in an interview.
Weber and colleagues developed a line curve that illustrates the severity of symptoms from onset to resolution. Skin and GI adverse events would occur earlier, between week 3 and 4 of treatment, and resolve earlier, perhaps by approximately week 10 of treatment.
Endocrine and hepatic toxicities would occur between 6 and 8 weeks of treatment; yet, while hepatic toxicities would eventually subside by about week 14, the endocrine toxicity remains steady.
“Even though the symptoms go away with replacement hormones, you can have long-term side effects from the endocrine toxicity of ipilimumab that could potentially last one’s whole life,” Weber said. “That being said, those patients feel fine. I’ve had patients on hormone replacement for 2, 3, 4, 5 years who went into remission or relapsed on ipilimumab in an adjuvant trial and are fine.”
Weber explained that patients experiencing endocrinologic side effects might present with fatigue, headache, or mental status changes, all of which could indicate hypophysitis or inflammation of the pituitary gland. Additionally, older men with low testosterone levels can present with some of the same side effects. If these side effects are encountered in patients receiving ipilimumab, Weber said he usually prescribes a brief course of the corticosteroid prednisone for several weeks followed by hormone replacement therapy.
Yervoy is commonly characterized by the manifestation of inflammatory conditions, known as immune-related AEs (irAEs). Typically, irAEs are low grade and manageable. The most frequent irAEs with ipilimumab are diarrhea, rash, fatigue, pruritus, and colitis. These events are suggested to be a consequence of ipilimumab-induced T-cell attack on normal tissues. The IrAEs can occur during treatment and/or develop weeks or even months after initiation of therapy. This is an important aspect of patient education for they need to relate these irAES to the Yervoy even several months to years after their Yervoy infusion. Early patient reporting of irAEs is also an important aspect of the patient education. The earlier a patient reports a side effect, the earlier an intervention can be prescribed, limiting the patient’s toxicity. Yervoy treatments require effective communication between patients and their healthcare providers to help patients develop an awareness of what can be expected during treatment, including the probability of experiencing novel irAEs.
Prescribing information for irAEs for ipilimumab recommend the use of corticosteroids for management of moderate-to-severe AEs to reduce the risk of serious complications. The use of corticosteroids does not diminish the clinical efficacy of ipilimumab and has been studied in clinical trials. Tapering of corticosteroids should occur over a 1-month period, but oftentimes it requires frequent communication with patients to prevent recurrence of symptoms as they are tapered off the corticosteroids. Reviewing of each symptom cluster aids clinicians during their assessment to differentiate between treatment and nontreatment related symptoms.
Prompt reporting of potential irAEs is important for effective management. Oncology nurses play a central role in ensuring that patients are aware of irAEs and alert to AEs, which may require further evaluation, as well as in educating patients on the need for early identification and reporting of these events.
Intravenous calcium plus magnesium (IV CaMg) given before or after adjuvant FOLFOX chemotherapy has absolutely no effect on the development of sensory neurotoxicity induced by oxaliplatin, new research shows. Findings were presented during the ESMO 15th World Congress on Gastrointestinal Cancer. Abstract 0-0032
Axel Grothey, MD, professor of Oncology at the Mayo Clinic in Rochester, Minnesota, and multicenter colleagues found that IV CaMg has no effect on any aspect of sensory neuropathy commonly seen in patients who receive oxaliplatin-based chemotherapy relative to placebo controls.
The N08CB prospective, randomized, phase III study enrolled 362 patients with colon cancer who were undergoing adjuvant FOLFOX chemotherapy. Patients were randomized to one of three treatment arms. The first arm received IV CaMg (1 g calcium gluconate and 1 g magnesium sulfate) before and after chemotherapy. The second group received IV placebo before and after chemotherapy, and the third received IV CaMg prior to chemotherapy but placebo after chemotherapy.
The primary endpoint was cumulative sensory neurotoxicity as repeatedly measured by the sensory subscale of the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire–Chemotherapy-Induced Peripheral Neuropathy (EORTC QLQ-CIPN20) scale. Secondary endpoints using the Common Terminology Criteria for Adverse Events (CTCAE 4.0) and an oxaliplatinspecific neurotoxicity scale were also assessed. Acute neuropathy data were also collected for 5 days following each oxaliplatin dose.
The curves mirroring the overall incidence of sensory neuropathy in each of the three treatment arms were virtually superimposable across 12 treatment cycles, Grothey said.
Time to the development of grade 2 sensory neuropathy was also not significantly different between the three treatment arms. Changes in measurements reflecting sensitivity to touching cold items as well as discomfort swallowing cold liquids were also similar across all treatment groups, Grothey reported, as were scores measuring throat discomfort and muscle cramps.
Importantly, there were no significant differences between arms regarding the doses of oxaliplatin administered or discontinuation rates from chemotherapy, and no substantial differences in acute neuropathy scores or side effects were seen between the three study arms.
“Neurotoxicity is actually the dose-limiting toxicity of oxaliplatin—the longer we treat patients with it, the more likely they will develop neurotoxicity, and it can be disabling,” Grothey said. Unlike other chemotherapy-induced side effects, such as diarrhea and hair loss, “neurotoxicity can also stick around for months and sometimes years, and some patients never recover from it, particularly when we are treating in a palliative setting,” he added.
Whereas other chemotherapy agents are associated with neurotoxicity, certain types of neuropathy associated with oxaliplatin are unique to the drug. For example, some patients develop sensitivity to cold, which can be quite burdensome. Patients can also develop jaw spasms and throat discomfort that are again unique to oxaliplatin, Grothey continued.
“There were a lot of trials showing an inconsistent effect, so there was a need to have a definitive study,” said Grothey. “We now have that definitive study, and it shows IV CaMg does not work to prevent oxaliplatin-induced neurotoxicity. This should be the nail in the coffin for using IV CaMg as a neuroprotectant against oxaliplatin-induced acute and chronic neurotoxicity.”
The pendulum is swinging again. Those of us who have been oncology nurses for awhile have seen this pendulum swing one way and then back the other way several times already. In 2004, a trial by Laurence Gamelin et al concluded that calcium and magnesium infusion significantly reduced the incidence and severity of peripheral neuropathy secondary to oxaliplatin. (Clin Cancer Res. 2004;10(12):4055-4061) After this, it became standard of care to administer 1 g of calcium gluconate and 1 g of magnesium sulfate both pre- and post-oxaliplatin.
Fast forward to 2007 and the CONcePT (Combined Oxaliplatin Neurotoxicity Prevention Trial) study, a clinical trial of 160 patients who were given calcium/ magnesium infusion to reduce neurotoxicity. This trial was prematurely terminated after 2 years, because the independent data-monitoring committee found that the calcium/magnesium reduced the efficacy of the chemotherapy—in some cases, response rates could be reduced up to 52% based on their central radiology review. Once this was reported, it became almost unethical to administer calcium/magnesium to patients. As a side note, despite being stopped early, the CONcePT trial did demonstrate that the calcium/magnesium infusions delayed the time to onset of grade 2 sensory neural toxicity. However, due to concerns about decreased efficacy of the chemotherapy, we did not administer calcium/magnesium to any patients.
At the 2008 ASCO Gastrointestinal Cancers Symposium, Howard Hochster, MD, professor of Medicine at the Yale School of Medicine, presented a new analysis that emerged from a central, blinded radiology review of scans in 139 patients enrolled in the CONcePT trial (Abstract 280). Based on the central radiology review, the response rate favored patients treated with calcium/magnesium. Although the difference was not significant, it contradicted the data-monitoring committee’s analysis that had previously shut down the trial. Based on this presentation, magnesium/calcium was back in favor with many clinicians.
In our practice, it was decided to err on the side of caution and only administer calcium/magnesium routinely to those patients with metastatic disease. Unlike those patients being treated in the adjuvant setting, cure was not considered realistic, so any lingering concerns about decreasing efficacy of the chemotherapy were not as worrisome.
Furthermore, these patients would need treatment for a longer period of time, and delaying neurotoxicity would allow for more oxaliplatin. We did use calcium/ magnesium sporadically for those patients being treated adjuvantly who experienced severe, acute neurotoxicity (eg, pharyngolaryngeal dysesthesia), usually related to exposure to cold. This appeared to help several patients manage this symptom.
Now, yet a new study was reported, which failed to demonstrate any activity of calcium/magnesium as a neuroprotectant against oxaliplatin-induced neurotoxicity— neither acute nor chronic. The recommendation now is not to use it as it is ineffective.
So, where does that leave us? Each clinician will need to interpret the data and make his or her own conclusion. Because we have seen it help some patients with the acute, cold-induced dysesthesias, we will likely continue to use it in those specific cases. I think it just goes to show, once again, how careful one must be in changing practice based on one study, as it may be contradicted in the next one!
A multisite, randomized, double-blind trial evaluating the fatigue-ameliorating properties of American ginseng in cancer patients and recent survivors has found the herb to be helpful in reducing some aspects of cancer-related fatigue (CRF), with the benefit strongest among patients currently in treatment. (J Natl Cancer Inst. 2013; doi: 10.1093/jnci/ djt181)
Encouraging results from two earlier pilot studies of Asian and American ginseng, respectively, suggested that the herb has the potential to help alleviate CRF, which is one of the most prevalent and activity-restricting symptoms patients and survivors face. Preclinical studies also have shown both a link between CRF and inflammation, as well as anti-inflammatory properties associated with ginseng.
For this trial, under the auspices of the North Central Cancer Treatment Group and the Mayo Clinic in Rochester, Minnesota, researchers tested the efficacy of 2000 mg daily of American ginseng in alleviating CRF. Both the Asian (Panax ginseng) and American (Panax quinquefolius) species have a similar mix of active ingredients, but amounts and strengths do vary between the species.
TA total of 364 patients at 40 different sites— the majority of which were community cancer centers—received either twice-daily ginseng or placebo over an 8-week period. All tumor types were eligible, with the exception of brain cancer and central nervous system lymphoma; to be eligible for the study, patients needed to be in curative treatment or have been treated within the past two years, with a baseline CRF score ≥4 (on an 11-point scale where 0 is “no fatigue” and 10 equal to “as bad as it can be”). Those who had previously used ginseng or other agents for fatigue were not eligible, and for patients currently in treatment, there could be no changes planned in their regimens over the course of the 8-week study period.
The study’s primary endpoint was patient ratings on the Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF), with assessments carried out at baseline and at weeks 4 and 8. Other outcomes examined included the Profile of Mood States (POMS) and the Brief Fatigue Inventory (BFI). To make outcome comparisons more straightforward across the different instruments, researchers converted scores to a 100-point scale, with higher numbers meaning less fatigue.
At 4 weeks, patients in the ginseng cohort showed a change from baseline on the MFSI-SF of 14.4 versus 8.2 in the placebo group, and a statistically significant fatigue improvement of 20 versus 10.3, respectively, at 8 weeks. The researchers noted that this finding suggests that clinically meaningful results from ginseng (defined as a difference of ≥10 points on the 100-point scale) may not appear until 2 months after starting it.
Looking at the other measures, patients in the ginseng arm showed statistically significant improvements on the fatigue-inertia subscale of the MFSI-SF and the vigor-activity subscale of the POMS, but not on the BFI total score or activity interference measures.
A planned subset analysis compared the effect of the ginseng intervention in patients currently in treatment with those who had completed it. This analysis demonstrated that patients who were currently receiving chemotherapy and/or radiation had better fatigue scores in the ginseng group than did those in the placebo arm, and this was true at both the 4- and 8-week intervals.
Investigators also wanted to determine toxicities related to ginseng, so side-effect data were collected from patients using weekly self-report questionnaires, and from providers, using the Common Terminology Criteria for Adverse Events (CTCAE). No significant differences in patient-reported toxicities or provider CTCAE grading were seen between the two study arms.
The researchers noted that this finding conforms to earlier research on the herb corroborating its safety, though they cautioned that ginseng’s characteristics and estrogenic properties depend on how it is extracted. The American (Wisconsin) ginseng used in this study was water-extracted, a method that has shown some breast cancer cell inhibition in preclinical research, whereas ginseng products derived from methanol extraction exhibit estrogenic properties that have been found to increase breast cancer cells in in vitro studies.
One important limitation of the study, the authors noted, is the 8-week duration of the trial, so that long-term or continued efficacy of ginseng for CRF remains unknown.
Overall, the researchers reported that more patients responded positively to the ginseng intervention and demonstrated a strong clinical benefit equivalent to a ≥30% improvement compared with those on placebo, a finding that suggests a need for additional research on the herb’s efficacy in ameliorating CRF, as well as work toward a safe, standardized, accessible ginseng product, which is currently not subject to FDA regulation.
Although pazopanib (Votrient) and sunitinib (Sutent) are relatively similar in terms of efficacy in the treatment of advanced renal cell carcinoma, the former appears to cause fewer toxic side effects than the latter, suggesting that patients could experience a greater quality of life with pazopanib as opposed to sunitinib with the same treatment benefit, according to results of a phase III trial. (N Engl J Med. 2013;369(8):722-731)
The study found that pazopanib was noninferior to sunitinib in terms of progression-free survival (hazard ratio [HR] = 1.05; 95% CI, 0.90- 1.22), falling within the predefined noninferiority margin (upper bound of 95% CI, <1.25). The overall survival also was similar (HR = 0.91; 95% CI, 0.76-1.08).
In terms of the adverse-event profile, the study found that patients who received sunitinib versus pazopanib experienced a higher incidence of fatigue (63% vs 55%), hand-foot syndrome (50% vs 29%), and thrombocytopenia (78% vs 41%). Patients who received pazopanib had a greater incidence (60% vs 43%) of elevated levels of alanine aminotransferase, a sign that the patient might have experienced liver damage.
The study also found that the mean change from baseline in 11 of 14 health-related qualityof- life areas, including those involving fatigue or soreness in the mouth, throat, hands, or feet, favored pazopanib during the first 6 months of treatment (P <.05). Of the 11 comparisons, mouth and throat soreness showed the largest difference, with an effect size in the medium-to large range (0.50-0.80), the study authors noted.