Adult Cancer Pain, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology.

In recent years, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adult Cancer Pain have undergone substantial revisions focusing on the appropriate and safe prescription of opioid analgesics, optimization of nonopioid analgesics and adjuvant medications, and integration of nonpharmacologic methods of cancer pain management. This selection highlights some of these changes, covering topics on management of adult cancer pain including pharmacologic interventions, nonpharmacologic interventions, and treatment of specific cancer pain syndromes. The complete version of the NCCN Guidelines for Adult Cancer Pain addresses additional aspects of this topic, including pathophysiologic classification of cancer pain syndromes, comprehensive pain assessment, management of pain crisis, ongoing care for cancer pain, pain in cancer survivors, and specialty consultations.

Nausea and vomiting in advanced cancer: the Cleveland Clinic protocol.

Nausea and vomiting are common and distressing symptoms in advanced cancer. Both are multifactorial and cause significant morbidity, nutritional failure, and reduced quality of life. Assessment includes a detailed history, physical examination and investigations for reversible causes. Assessment and management will be influenced by performance status, prognosis, and goals of care. Several drug classes are effective with some having the added benefit of multiple routes of administration. It is our institution's practice to recommend metoclopramide as the first drug with haloperidol as an alternative antiemetic. Dexamethasone should be used for patients with central nervous system metastases or bowel obstruction. If your patient is near death, empiric metoclopramide, haloperidol or chlorpromazine is used without further investigation. For patients with a better prognosis, we exclude reversible causes and use the same first-line antiemetics, metoclopramide and haloperidol. For those who do not respond to first-line single antiemetics, olanzapine is second line and ondansetron is third. Rarely do we use combination therapy or cannabinoids. Olanzapine as a single agent has a distinct advantage over antiemetic combinations. It improves compliance, reduces drug interactions and has several routes of administration. Antiemetics, anticholinergics, octreotide and dexamethasone are used in combination to treat bowel obstruction. In opiod-na'ive patients, we prefer haloperidol, glycopyrrolate and an opioid as the first-line treatment and add or substitute octreotide and dexamethasone in those who do not respond. Non-pharmacologic interventions (mechanical stents and percutaneous endoscopic gastrostomy tubes) are used when nausea is refractory to medical management or for home-going management to relieve symptoms, reduce drug costs and rehospitalization.

Real-World Outcomes of Everolimus and Exemestane for the Treatment of Metastatic Hormone Receptor-Positive Breast Cancer in Patients Previously Treated With CDK4/6 Inhibitors.

PURPOSE: Everolimus with exemestane (EVE+EXE) was FDA-approved to treat metastatic hormone receptor-positive breast cancer (mHRBC) based on BOLERO-2. However, none of those patients received prior CDK4/6 inhibitors. The purpose of this study is to evaluate the efficacy of EVE+EXE in mHRBC after CDK4/6 inhibitors. METHODS: A retrospective review of patients ≥18 years old with mHRBC treated with EVE+EXE, for ≥30 days, at our institution from January 1, 2012, to April 1, 2020 was conducted. Primary objective was to compare progression free survival (PFS) for EVE+EXE between patients with and without prior exposure to CDK4/6 inhibitors. Secondary outcomes included overall survival and safety. RESULTS: 192 patients were included in the study (n = 79, prior CDK4/6 inhibitor use; n = 113, no prior CDK4/6 inhibitor use). Baseline patient characteristics were similar between groups. Greater number of prior therapies before EVE+EXE use increased risk of disease progression (P = .017). Patients with prior CDK4/6 inhibitor use had a lower median PFS of 3.8 months (95% CI: 3.4-4.7) vs. 5.4 months (95% CI: 3.9-6.2) for patients without prior CDK4/6 inhibitor use, with a HR for progression of 1.46 (95% CI: 1.08 to 1.97, P = .013). Overall survival between groups was not significantly different. CONCLUSION: Patients who received a prior CDK4/6 inhibitor had a lower median PFS benefit from EVE+EXE compared to those who did not, without differences in overall survival. Although PFS is expected to decrease with subsequent lines of therapy, it is reasonable to use EVE+EXE after CDK4/6 inhibitors in selected patients, recognizing that additional benefit is modest.

"If You Call Them, They Will Come": A Telephone Call Reminder to Decrease the No-Show Rate in an Outpatient Palliative Medicine Clinic.

INTRODUCTION: A high outpatient clinic no-show rate affects clinical outcomes, increases healthcare costs, and reduces both access to care and provider productivity. In an effort to reduce the no-show rate at a busy palliative medicine outpatient clinic, a quality improvement project was launched consisting of a telephone call made by clinic staff prior to appointments. The study aimed to determine the effect of this intervention on the no-show rate, and assess the financial impact of a decreased no-show rate. METHODS AND MATERIALS: The outpatient clinic no-show rate was measured from September 1 to December 31, 2015. Data from the first 8 months of the calendar year was removed since these could not be verified. Starting January 1, 2016, patients received a telephone call reminder 24 hours prior to their scheduled outpatient appointment for confirmation. No-show rate was again measured for the calendar year 2016. Opportunity costs were calculated for unfulfilled clinic visits. RESULTS: Of the 1224 completed visits from September 1 to December 31, 2015, 271 were no-shows with an average rate of 11.8%. After the intervention, there were 4368 completed visits and 562 no-shows. The no-show rate for 2016 averaged 6.9% (p < 0.001), down 4.9% from the last 4 months of 2015. Estimated opportunity costs were about 396 no-show visits avoided, equivalent to an annual savings of about $79,200. CONCLUSION: A telephone call reminder to patients 24 hours prior to their appointment decreased the no-show rate in an outpatient palliative medicine clinic. Avoiding unfulfilled visits resulted in substantial opportunity costs.

The intravenous to oral relative milligram potency ratio of morphine during chronic dosing in cancer pain.

Morphine (M) is the opioid analgesic of choice for severe cancer pain. The IV to PO M equipotent switch ratio (CR) is controversial. We designed this prospective observational cohort to confirm the efficacy and safety of M IV to PO CR of 1:3. Consecutive cancer patients admitted to an inpatient palliative medicine unit were screened for inclusion. Pain was managed by palliative medicine specialists. They were blinded to the patient data collected, and the calculated CR. The switch was considered successful if the following criteria were met: (1) Pain adequately controlled: pain rated as none or mild (2) Number of RD less than 4 (for non incident pain) per 24 hours (3) No limiting side effects. We used Day 3 ATC M dose for CR calculations. The major outcome measures were the IV : PO CR ratio, morphine doses (mg/day), pain severity, number of PRN doses, and day 1 and day 3side effects. Descriptive statistics were used to report mean, median, standard deviation and range of different variables. Two hundred and fifty six consecutive admissions were screened, and 106 were eligible for the study. Sixty two underwent a successful M route switch and were included in this analysis. A ratio of 1:3 was safely implemented over a wide M dose range. About 80% were successfully switched with a calculated CR of 1:3. 20% required an oral M dose adjustment after route switch either to better pain control or reduce side effects with a resultant higher (e.g. 1:4) or lower (e.g. 1:2) calculated potency ratios respectively. A potency ratio of 1:3 was safe as evaluated by common M side-effects, the dose also easy to calculate. The 1: 3 M IV to PO relative milligram potency ratio appears correct and practical for most patients over a wide M dose range.

Components of the anorexia-cachexia syndrome: gastrointestinal symptom correlates of cancer anorexia.

INTRODUCTION: Cancer-related anorexia is traditionally considered part of a complex but ill-defined anorexia-cachexia syndrome in which anorexia is intimately associated with other gastrointestinal (GI) symptoms and weight loss. We surveyed cancer patients with anorexia to learn more about the relationship between anorexia and these symptoms. MATERIALS AND METHODS: A 22-item GI questionnaire assessed the severity of anorexia and the prevalence of concurrent GI symptoms, including taste changes, food aversions, altered sense of smell, and diurnal food intake changes. The relationship between anorexia severity and anticancer therapy and prior menstrual or pregnancy-related appetite changes was also assessed. RESULTS: Ninety-five of 101 patients with anorexia surveyed had complete data. Seventy-eight percent of them had moderate or severe anorexia. Abnormal diurnal appetite variation, taste changes, and food aversions were present in over 50% of all those with anorexia. Judged by the numerical rating scale, the worse the anorexia, the more prevalent were early satiety, constipation, vomiting, and food aversions. Those with more severe anorexia had greater weight loss, and worse performance status. Anorexia severity did not correlate with that during prior menses/pregnancy or antitumor therapy. CONCLUSIONS: Evaluation of multiple other GI symptoms is important in understanding the total experience of cancer anorexia. Early satiety, taste changes, food aversions, and altered sense of smell are important accompanying GI symptoms. Most validated anorexia tools do not assess these commonly associated GI symptoms. Future research should develop a comprehensive anorexia symptom questionnaire.

Narrative review: furosemide for hypercalcemia: an unproven yet common practice.

Although primary hyperparathyroidism is the most common cause of hypercalcemia, cancer is the most common cause requiring inpatient intervention. An estimated 10% to 20% of all patients with cancer have hypercalcemia at some point in their disease trajectory, particularly in advanced disease. Aggressive saline hydration and varying doses of furosemide continue to be the standard of care for emergency management. However, a review of the evidence for the use of furosemide in the medical management of hypercalcemia yields only case reports published before the introduction of bisphosphonates, in contrast to multiple randomized, controlled trials supporting the use of bisphosphonates. The use of furosemide in the management of hypercalcemia should no longer be recommended.

A day in the life: a case series of acute care palliative medicine--the Cleveland model.

Palliative care in advanced disease is complex. Knowledge and experience of symptom control and management of multiple complications are essential. An interdisciplinary team is also required to meet the medical and psychosocial needs in life-limiting illness. Acute care palliative medicine is a new concept in the spectrum of palliative care services. Acute care palliative medicine, integrated into a tertiary academic medical center, provides expert medical management and specialized care as part of the spectrum of acute medical care services to this challenging patient population. The authors describe a case series to provide a snapshot of a typical day in an acute care inpatient palliative medicine unit. The cases illustrate the sophisticated medical care involved for each individual and the important skill sets of the palliative medicine specialist required to provide high-quality acute medical care for the very ill.

Acute inpatient palliative medicine in a cancer center: clinical problems and medical interventions--a prospective study.

The clinical characteristics and medical interventions of the 100 consecutive cancer admissions to the acute care inpatient palliative medicine unit at the Cleveland Clinic for 2 months are described. Median age was 62 years (range, 31 to 92 years). The male-female ratio was 1:1. Most admissions were referred by hematology-oncology and had prior antineoplastic therapy. Reasons for admission were symptom control and cancer-related complications. Patients underwent invasive diagnostic and therapeutic procedures, hydration, transfusions, radiation, or chemotherapy, or a combination, during their admission. Most were discharged home with hospice care or had outpatient clinic follow-up. The mortality rate was 20%. Aggressive multidisciplinary management of symptoms, disease complications, comorbid conditions, and psychosocial problems were provided. Palliative medicine physicians provided continuity of care in the outpatient clinic and at home. An acute inpatient palliative medicine unit within a tertiary level medical center has a definable and important role in comprehensive cancer care.

The business of palliative medicine - part 5: service utilization in a comprehensive integrated program.

The aim of palliative medicine is to provide multidisciplinary comprehensive care in advanced illness. Patient and family utilization of various product service lines offered by the Harry R Horvitz Center for Palliative Medicine at the Cleveland Clinic Foundation was studied. Newly referred patients were followed up prospectively until 85% had either died or been lost to follow-up. Demographic, clinical, and referral data were recorded; subsequent product service line utilization was updated daily. The total study period was 171 days, and 238 patients entered. Acute care inpatient unit, outpatient clinic visits, and 24-hour phone contacts were the most frequently used product service lines. Patients had a median of 3 contacts (range, 1 to 27) with individual service lines. Multiple palliative medicine product service lines were utilized often, with repeated use of the individual service lines. A comprehensive integrated palliative medicine program is necessary to fully meet the complex needs of those with advanced disease.

Single-Dose Fluconazole Therapy for Oral Thrush in Hospice and Palliative Medicine Patients.

BACKGROUND: Oral thrush is a common fungal infection of the mouth experienced by palliative medicine and hospice patients who have advanced cancer. Individuals often experience distressing symptoms that affect their oral intake with most regimens adding to pill burden. This is an open-label prospective observational study to assess the efficacy of a single-dose fluconazole 150 mg for oral thrush. METHODS: Palliative medicine and hospice patients with a clinical diagnosis of oral thrush, a life expectancy of more than 1 week, and were able to swallow were enrolled. Signs and symptoms were evaluated on day 1 prior to administration of 150 mg of fluconazole and between days 3 to 5 after treatment. RESULTS: Of 57 patients, 55 (96.5%) had more than 50% improvement in signs and symptoms. Both the number and severity of symptoms changed significantly posttreatment ( P < .001). Side effects were few. CONCLUSION: Single-dose fluconazole 150 mg is an effective treatment of oral thrush for individuals with advanced cancer.

Systematic review of the treatment of cancer-associated anorexia and weight loss.

PURPOSE: We systematically assessed the efficacy and safety of appetite stimulants in the management of cancer-related anorexia. Literature databases were searched for randomized controlled trials of appetite stimulants in the treatment of cancer anorexia. MATERIALS AND METHODS: Studies were graded according to quality. Fifty-five studies met inclusion criteria. RESULTS: Only two drugs have evidence to support their use for anorexia (progestins and corticosteroids). There is strong evidence against the use of hydrazine sulfate. The outcomes of these trials have been mixed and patient population heterogeneous. CONCLUSION: The optimal dose, time to start, and duration of treatment for many appetite stimulants for cancer anorexia is still unknown. A more systematic approach to research methodology with universal outcome measure and prospective randomized studies are need. Combination regimens are needed but this cannot at the present time be supported by the data presented.

Deaths in an academic medical center.

The number of inpatient deaths in a calendar year in an academic medical center was reviewed from a computerized database. The total number was 1222. The median length of hospital stay for those who died was 7 days (range, 1-190); 404 (33%) were 75 years or older. There were 678 (55%) males and 544 (45%) females. The pulmonary medicine service had the most deaths with 290 (24%) followed by hematology/oncology 230 (18%). The most common primary diagnoses in the decedents were subendocardial infarction 58 (5%), congestive heart failure 57 (5%), and pneumonia 45 (4%). The most common diagnostic-related groups (DRGs) were respiratory system disorders (475), 98 (8%); tracheostomy (483), 75 (6%); and heart surgery (110), 65 (5%). Frequent procedures done prior to death were mechanical ventilation (<96 hours) 101 (8%), and mechanical ventilation (>96 hours) 55 (5%), and tracheostomy 54 (4%). Invasive procedures were common. Forty-five percent of the predeath patient days were spent in intensive care units. Palliative medicine was involved in the care of 20% of all the decedents.

'I'm not that sick!' Overcoming the barriers to hospice discussions.

Hospice programs care for patients facing life-limiting illness. Although patients and family members report that they are satisfied once they are enrolled in a hospice service, many patients are referred late or not at all. Several barriers and misconceptions about hospice likely contribute to its underuse. We explore these issues and provide guidance to more effectively communicate with patients about hospice services.

Appetite and cancer-associated anorexia: a review.

Appetite is governed by peripheral hormones and central neurotransmitters that act on the arcuate nucleus of the hypothalamus and nucleus tactus solitarius of the brainstem. Cancer anorexia appears to be the result of an imbalance between neuropeptide-Y and pro-opiomelanocortin signals favoring pro-opiomelanocortin. Many of the appetite stimulants redress this imbalance. Most of our understanding of appetite neurophysiology and tumor-associated anorexia is derived from animals and has not been verified in humans. There have been few clinical trials and very little translational research on anorexia despite its prevalence in cancer.

Opioid rotation in cancer patients: pros and cons.

Opioid rotation involves changing from one opioid to another using correct equianalgesic conversion techniques to achieve better analgesia and/or fewer side effects. The strategy appears to work because of significant interindividual variations in response to both analgesic activity and toxicity. Although there are many retrospective studies, few prospective controlled trials of opioid rotation have been published. The practical and theoretical advantages of opioid rotation include improved analgesia, reduced side effects, cost reduction, and improved compliance. Disadvantages include problems related to inaccurate conversion tables, limited availability of certain opioid formulations, drug interactions, and the possibility of increased expense. Weighing the advantages and disadvantages is essential prior to making a decision about opioid rotation selection.

Common symptoms in advanced cancer.

The key points of this article are anorexia and cachexia are: A major cause of cancer deaths. Several drugs are available to treat anorexia and cachexia. Dyspnea in cancer usually is caused by several factors. Treatment consists of reversing underlying causes, empiric bronchodilators, cortico-steroids--and in the terminally ill patients-opioids, benzodiazepines,and chlorpromazine. Delirium is associated with advanced cancer. Empiric treatment with neuroleptics while evaluating for reversible causes is a reasonable approach to management. Nausea and vomiting are caused by extra-abdominal factors (drugs,electrolyte abnormalities, central nervous system metastases) or intra-abdominal factors (gastroparesis, ileus, gastric outlet obstruction, bowel obstruction). The pattern of nausea and vomiting differs depending upon whether the cause is extra- or intra-abdominal. Reversible causes should be sought and empiric metoclopramide or haloperidol should be initiated. Fatigue may be caused by anemia, depression, endocrine abnormalities,or electrolyte disturbances that should be treated before using empiric methylphenidate. Constipation should be treated with laxatives and stool softeners. Both should start with the first opioid dose.

The financial benefits of acute inpatient palliative medicine: an inter-institutional comparative analysis by all patient refined-diagnosis related group and case mix index.

Financial comparisons of acute care hospital services are possible using the Centers for Medicare & Medicaid Services case mix index (CMI) and All Patient Refined-Diagnosis Related Group (APR-DRG) data. We compared The Cleveland Clinic's Inpatient Palliative Medicine (CCIPM) acute care unit's CMI and APR-DRG data with national and peer institution data. Total mean charges per admission to the CCIPM unit were 7,800 dollars lower than at other peer institutions despite an equivalent severity of illness and longer length of stay and higher mortality in the CCIPM unit. The lower charges were due primarily to lower laboratory and pharmaceutical charges. We conclude that an acute inpatient palliative medicine unit operating within a comprehensive integrated palliative medicine program is cost-effective in providing specialized care for people with advanced disease.

Opioids in cancer pain: common dosing errors.

Many individuals with advanced malignancy continue to suffer from pain and, consequently, impaired quality of life. The clinical scenarios in advanced cancer pain are complex, and successful management may require a more sophisticated and individualized approach than suggested by the World Health Organization guidelines. In patients referred to the Harry R. Horvitz Center for Palliative Medicine in Cleveland, numerous commonly occurring errors in opioid use have been noted. This article describes these errors and offers strategies with which to improve outcomes for patients suffering with cancer pain.

Management of cough in advanced cancer.

Cough is a common symptom in cancer, with causes that can be benign or malignant. When severe, it affects patients' quality of life and well being. Treatment begins with a detailed history and careful physical examination, followed by chest imaging. Managing cough is directed at correcting the reversible causes. Empiric treatment of cough is valuable in both reversible and irreversible causes. We prefer hydrocodone as first-line empiric treatment, but when the cough is resistant to this, our second-line therapy would be the addition or substitution of benzonatate. Bronchodilators, as well as corticosteroids, are commonly employed in our practice and can be useful in unsuspected bronchospasm.