Work loss and activity impairment due to extended nausea and vomiting in patients with breast cancer receiving CINV prophylaxis.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV)'s impact on work loss remains poorly described. We evaluated associations between the duration of CINV episodes, CINV-related work loss (CINV-WL), and CINV-related activity impairment (CINV-AI) in patients with breast cancer receiving highly emetogenic chemotherapy. METHODS: We analyzed data from a prospective CINV prophylaxis trial of netupitant/palonestron and dexamethasone for patients receiving an anthracycline and cyclophosphamide (AC) for breast cancer (NCT0340371). Over the observed CINV duration (0-5 days), we analyzed patient-reported CINV-WL and CINV-AI for the first two chemotherapy cycles. We categorized patients as having either extended (≥ 3 days) or short (1-2 days) CINV duration and quantified its impact on work using the Work Productivity and Activity Impairment Questionnaire (WPAI). RESULTS: Overall, we captured data for 792 cycles in 402 women, including 136 (33.8%) employed patients with 35.3% reporting CINV. Of those with CINV, patients reported CINV-WL in 26 cycles and CINV-AI in 142 cycles. Of those with CINV, 55.3% of extended CINV cycles experienced CINV-WL compared to 16.7% of short CINV cycles (p < 0.001). The relative risk of CINV-WL between extended and short CINV was 3.32 (p < 0.01) for employed patients. The mean difference in CINV-AI scores (higher = worse) between extended and short duration CINV was 5.0 vs. 3.0 (p < 0.001). CONCLUSION: Extended (≥ 3 days) CINV was associated with more than triple the risk of CINV-WL and higher CINV-AI compared with short CINV.

Nausea and Vomiting Not Related to Cancer Therapy: Intractable Problem or Clinical Challenge?

PURPOSE: Unlike therapy-related nausea and vomiting (chemotherapy or radiotherapy induced), nausea and vomiting (N/V) in patients with advanced cancer is often multicausal and thus presents unique challenges. Few professional guidelines address the palliative management of N/V, and those that do are insufficiently detailed to bolster clinical decision-making. Nonetheless, oncology advanced practitioners (APs) are frequently challenged to manage these high-impact symptoms. This requires collaborating with other oncology care providers and cultivating a knowledge base to educate and mentor professional colleagues to optimize N/V unrelated to treatment. METHODS: Literature reviewed included current and classic articles that address the physiologic bases of N/V related to disease and with malignant bowel obstruction, agents used to alleviate nausea or N/V, and nonpharmacologic adjunctive measures. This information was framed within palliative care and symptom management clinical experience. RESULTS: This review article summarizes what is known about the neuropharmacology of N/V in advanced disease. Focused assessment, pharmacologic agents (antiemetics, central neuromodulators, and peripheral prokinetic agents), and nondrug adjunctive measures that may be useful for N/V are included. CONCLUSIONS: Managing N/V in advanced cancer is a quality-of-life imperative that requires persistence and interprofessional collaboration among oncology APs and other clinicians to personalize management. This work can change the perception that N/V related to progressive disease is frequently intractable to one that considers it as a manageable clinical challenge.

Phase IIIb Safety and Efficacy of Intravenous NEPA for Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Patients with Breast Cancer Receiving Initial and Repeat Cycles of Anthracycline and Cyclophosphamide (AC) Chemotherapy.

BACKGROUND: NEPA, a combination antiemetic of a neurokinin-1 (NK1 ) receptor antagonist (RA) (netupitant [oral]/fosnetupitant [intravenous; IV]) and 5-HT3 RA, palonosetron] offers 5-day CINV prevention with a single dose. Fosnetupitant solution contains no allergenic excipients, surfactant, emulsifier, or solubility enhancer. A phase III study of patients receiving cisplatin found no infusion-site or anaphylactic reactions related to IV NEPA. However, hypersensitivity reactions and anaphylaxis have been reported with other IV NK1 RAs, particularly fosaprepitant in patients receiving anthracycline-cyclophosphamide (AC)-based chemotherapy. This study evaluated the safety and efficacy of IV NEPA in the AC setting. MATERIALS AND METHODS: This phase IIIb, multinational, randomized, double-blind study enrolled females with breast cancer naive to highly or moderately emetogenic chemotherapy. Patients were randomized to receive a single 30-minute infusion of IV NEPA or single oral NEPA capsule on day 1 prior to AC, in repeated (up to 4) cycles. Oral dexamethasone was given to all patients on day 1 only. RESULTS: A total of 402 patients were included. The adverse event (AE) profiles were similar for IV and oral NEPA and consistent with those expected. Most AEs were mild or moderate with a similarly low incidence of treatment-related AEs in both groups. There were no treatment-related injection-site AEs and no reports of hypersensitivity or anaphylaxis. The efficacy of IV and oral NEPA were similar, with high complete response (no emesis/no rescue) rates observed in cycle 1 (overall [0-120 hours] 73.0% IV NEPA, 77.3% oral NEPA) and maintained over subsequent cycles. CONCLUSION: IV NEPA was highly effective and safe with no associated hypersensitivity and injection-site reactions in patients receiving AC. IMPLICATIONS FOR PRACTICE: As a combination of a neurokinin-1 (NK1 ) receptor antagonist (RA) and 5-HT3 RA, NEPA offers 5-day chemotherapy-induced nausea and vomiting prevention with a single dose and an opportunity to improve adherence to antiemetic guidelines. In this randomized multinational phase IIIb study, intravenous (IV) NEPA (fosnetupitant/palonosetron) was safe and highly effective in patients receiving multiple cycles of anthracycline-cyclophosphamide (AC)-based chemotherapy. Unlike other IV NK1 RAs, the IV NEPA combination solution does not require any surfactant, emulsifier, or solubility enhancer and contains no allergenic excipients. Hypersensitivity reactions and anaphylaxis have been reported with other IV NK1 RAs, most commonly with fosaprepitant in the AC setting. Importantly, there were no injection-site or hypersensitivity reactions associated with IV NEPA.

Nausea and Vomiting: a Palliative Care Imperative.

PURPOSE OF REVIEW: This review was undertaken to survey recent literature for research reports and comprehensive clinical reviews addressing the pharmacologic management of nausea and vomiting (N&V) in advanced cancer. The goal was to integrate findings in a comprehensive article that incorporates palliative care concepts into antiemetic treatment. RECENT FINDINGS: There are few published studies of N&V in advanced cancer; such research may be limited by the multicausal nature of N&V and participant burden to patients with life-limiting disease. Most articles are written by oncologists who also specialize in palliative care, and those addressing adverse effects of drugs used as antiemetics are found in other literature. Articles addressing more novel therapies, like cannabinoids and medical marijuana, are uncommon in the oncology literature. N&V in patients with progressive or advanced cancer is often multicausal. Nausea is more common and persistent, and even mild nausea is bothersome and may cause anxiety or depression. The mechanisms of nausea and vomiting overlap, but different neural pathways constitute the final pathway for each-the brainstem for vomiting and higher brain regions for nausea. Common causes of N&V in advanced cancer include constipation, opioids, and malignant bowel obstruction. About 40% have undetermined causes and may be exacerbated by impaired gastric emptying, chemical imbalances, or other factors. Several drugs that have antiemetic effects and act at different receptors are used to palliate N&V. There is a paucity of research that supports palliative antiemetic choices, and other research is needed to define potential therapeutic strategies that capitalize on differences between nausea and vomiting.

Revisiting the physiology of nausea and vomiting-challenging the paradigm.

PURPOSE: The predominant neurotransmitters and receptors for acute and delayed chemotherapy-induced nausea and vomiting (CINV) are represented in the current paradigm, which reflects successful control of emesis. However, control of nausea (N) lags behind management of vomiting (V). This review aims to re-examine and incorporate new information about the mechanisms of V and N. METHODS: The initial literature search focused on CINV. Keywords in articles led to subsequent discovery of publications focused on N&V in other medical and scientific fields (e.g., gastroenterology, neurology, cannabinoid science, neuropharmacology, and motion sickness). Using keywords to identify other sources continued until no further recent, meaningful publications were found. RESULTS: More than 86% of references were from recent non-oncology journals and books, suggesting there are many areas for cross-fertilization research into mechanisms and management of N&V-particularly of N, which involves overlapping and dissimilar CNS areas from V. Information from cited articles was incorporated into visual representation of N&V, which is certainly not exhaustive but supports highly complex processes in the stomach and gut, the vagus nerve and spinal cord neurons, the nucleus tractus solitarii, and the anterior insular cortex and anterior cingulate cortex with input from the amygdala. CONCLUSIONS: These data support the idea that mechanisms for N, whatever the cause, must be highly similar. Continued research into nausea, including patient-reported evaluation and outcomes, is important; interventions for nausea could be considered adjuvants to current standard of care antiemetics and be individualized, depending on patient-reported efficacy and adverse effects and preferences.

Impact of Addition of Carboplatin AUC ≥ 4 to Antiemetic Guidelines for Triple Antiemetic Prophylaxis: A Gap in Quality of Care, Guideline Adoption, and Avoiding Acute Care.

PURPOSE: After ASCO and National Comprehensive Cancer Network guideline recommendations for triple antiemetic prophylaxis for carboplatin area under the curve (AUC) ≥ 4, and the publication of studies documenting avoidable acute care after chemotherapy involving nausea and vomiting (NV) and other toxicities, we studied clinician adherence to the guideline change and assessed avoidable acute-care use. METHODS: Using a large electronic health record database, we evaluated antiemetic prophylaxis as recommended in the guidelines and post-chemotherapy avoidable acute-care use (defined as involving any of NV or 8 other toxicities) for patients initiating carboplatin or other chemotherapy from October 2012 to August 2018. RESULTS: We identified 11,554 carboplatin courses. After the guideline change adding neurokinin-1 receptor antagonists (RAs) for carboplatin AUC ≥ 4, its use rose to 20% of courses from the prior average of 16%; virtually all courses also included a 5-HT3 RA plus dexamethasone. We found avoidable acute care in 23% of courses; one quarter of these events were associated with NV. Acute care rates after carboplatin mirrored those after other highly emetogenic chemotherapy or oxaliplatin and exceeded those after other chemotherapy regimens. The > 80% shortfall in adherence may have been caused by low awareness or acceptance of the guideline change and/or by poor awareness of avoidable acute-care use after carboplatin. CONCLUSION: Neurokinin-1 RA prophylaxis for carboplatin AUC ≥ 4 remains low and largely unchanged despite National Comprehensive Cancer Network and ASCO 2017 recommendations for inclusion. NV and avoidable acute care involving NV seen after carboplatin were consistent with other highly emetogenic chemotherapy. Clinician action is required to remediate incomplete prophylaxis and to no longer place patient outcomes, resources for cancer treatment, and clinician reimbursement at risk.

Secondary Analysis Research.

In secondary data analysis (SDA) studies, investigators use data collected by other researchers to address different questions. Like primary data researchers, SDA investigators must be knowledgeable about their research area to identify datasets that are a good fit for an SDA. Several sources of datasets may be useful for SDA, and examples of some of these will be discussed. Advanced practice providers must be aware of possible advantages, such as economic savings, the ability to examine clinically significant research questions in large datasets that may have been collected over time (longitudinal data), generating new hypotheses or clarifying research questions, and avoiding overburdening sensitive populations or investigating sensitive areas. When reading an SDA report, the reader should be able to determine that the authors identified the limitation or disadvantages of their research. For example, a primary dataset cannot "fit" an SDA researcher's study exactly, SDAs are inherently limited by the inability to definitively examine causality given their retrospective nature, and data may be too old to address current issues.

Managing Constipation in Adults With Cancer.

Constipation is common in individuals with cancer, occurring in almost 60% of patients overall. The incidence increases in patients with advanced disease, particularly in those receiving opioid analgesics or medications with anticholinergic properties. Constipation is not uniformly assessed and therefore not recognized and appropriately managed in many instances. This can increase patients' physical and psychological distress. Furthermore, there is scant research to support current management strategies for constipation. The objectives of this review are to explore the incidence of and risk factors for constipation in patients with cancer, to discuss the extent of the problem, to explore the nonpharmacologic and pharmacologic measures for constipation and fecal impaction, and to synthesize a laxative management. An extensive review of medical, pharmacy, and nursing literature was done to explore the physiology and pathogenesis of constipation; detail the mechanisms of action, onset of effect, approximate costs, and adverse effects of drugs for constipation; and condense clinical expert consensus recommendations for constipation, particularly in patients with cancer. Advanced practitioners (APs) and other clinicians play crucial roles in identifying individuals at risk for and experiencing constipation to help them use effective regimens, including over-the-counter laxatives, and perhaps adjunctive nondrug measures. Clinicians and patients must develop an agreed-upon language for identifying the severity and effects of constipation. In addition, both should understand which laxatives are most appropriate and which should be avoided for particular patients. Two prescription agents are also available, and understanding when they should be used is important for APs.

Cancer Pain Management: Opioid Analgesics, Part 2.

Opioid analgesics are the cornerstone of moderate to severe cancer pain management, and do not have ceiling doses unless unmanageable adverse effects occur. Oral, short-acting pure µ agonists such as morphine are most frequently used, but other agents and administration formulations allow finding the right opioid and dose for most patients. In addition, clinicians must understand the metabolism, pharmacokinetics, and elimination of particular drugs to individualize opioid selection, select initial doses, and appropriately escalate doses to satisfactory pain relief or uncontrollable toxicity. Anticipation and proactive management of possible adverse effects, particularly constipation, confusion or delirium, opioid-specific adverse effects, and opioid abuse, are also integral to primary and secondary prophylaxis and management.

Cancer Pain Management: Comprehensive Assessment and Nonopioid Analgesics, Part 1.

Pain is still undertreated and thus a significant problem for at least half of all cancer patients. Inadequately managed cancer pain may cause significant morbidity and even affect mortality, as well as patient quality of life. One enduring problem is suboptimal pain education in basic and advanced educational programs, and many myths and knowledge gaps persist. This article focuses on identifying and dispelling myths, thorough baseline and ongoing pain assessment, pain documentation, and interprofessional collaboration. It includes a comprehensive review of appropriate use of nonopioid analgesics-nonsteroidal anti-inflammatory agents and acetaminophen, and so-called adjuvant analgesics, such as antidepressants, anticonvulsants, and other drugs.

Evolving treatment paradigms for chemotherapy-induced nausea and vomiting.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is one of the most debilitating toxicities associated with cancer treatment. Although effective antiemetic agents are available, their use in practice often is suboptimal. METHODS: The author reviews the pathophysiology of CINV as well as the drug classes and cost considerations that should be incorporated into treatment planning. RESULTS: Several drug classes, including 5-hydroxytryptamine-3 receptor antagonists, neurokinin-1 receptor antagonists, and corticosteroids, are effective, especially when used in combination. Older antiemetic agents, such as prochlorperazine and metoclopramide, as well as olanzapine may provide reasonable alternatives in certain settings. CONCLUSIONS: Interventions for CINV should include standard-of-care antiemetics combined with corticosteroids. The cost of using older, less expensive antiemetics may be outweighed by the expenditures to rescue patients after suboptimal prophylaxis, as well as the indirect costs of missed work and lost productivity.

Osteoporosis related to disease or therapy in patients with cancer.

Osteoporosis is a major public health issue in the general population, particularly in postmenopausal women. Patients with cancer may not only be at risk for primary osteoporosis, but for secondary osteoporosis related to cancer therapies-particularly therapies that impair gonadal function, lead to loss of serum estrogen, and negatively affect bone turnover. Normal bone remodeling is influenced by the receptor activator for nuclear kappa-B ligand pathway, calcium, vitamin D, and other nutrition factors, as well as modifiable and nonmodifiable factors. Identifying which patients with cancer are at risk for bone mineral density loss is important and may include patients with breast or prostate cancer, some survivors of pediatric malignancies, and adults with other tumors. Nurses play a major role in identifying those patients and their risk for low-impact fractures, which can have a significant effect on patient morbidity and mortality. Counseling and teaching are central nursing functions, as well as safely administering therapies, particularly bisphosphonates and denosumab.

Best practice management of CINV in oncology patients: II. Antiemetic guidelines and rationale for use.

Antiemetic guidelines for chemotherapy-induced nausea and vomiting (CINV) are important to provide a framework for evidence-based care. Attention and adherence to guidelines can help to close the gap between practitioner prediction and patient experience of CINV. Recent updated recommendations have provided guidance on appropriate use of standard-of-care antiemetics--aprepitant, palonosetron, and other serotonin (5-hydroxytryptamine) type 3 (5-HT3) receptor antagonists and dexamethasone. Guidelines are also important, in that their use is often tied to Medicare or other third-party payment. Limitations of guidelines include an absence of provisions for moving patients up the risk ladder for CINV when they have a poor response to recommended antiemetic treatment, as well as an absence of recommendations for treatment beyond the first cycle of antiemetic therapy. Further work is needed to improve evidence-based care in CINV, including studies focusing on delayed CINV and studies in the palliative-care setting.

Vesicant extravasation from an implanted venous access port.

Vesicant extravasation can occur even in patients whose nurses have years of experience. Nurse-physician collaboration is key to appropriate management.