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.

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.

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.

Nausea and vomiting in advanced cancer.

Nausea and vomiting are very common symptoms in cancer both treatment and non-treatment related. Many complications of advanced cancer such as gastroparesis, bowel and outlet obstructions, and brain tumors may have nausea and vomiting or either symptom alone. In a non-obstructed situation, nausea may be more difficult to manage and is more objectionable to patients. There is little research on management of these symptoms except the literature on chemotherapy induced nausea where guidelines exist. This article will review the etiologies of nausea and vomiting in advanced cancer and the medications which have been used to treat them. An etiology based protocol to approach the symptom is outlined.

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.

Delirium in palliative medicine: a review.

Delirium is a devastating complication of general medical and surgical populations but of particular importance in palliative medicine. It is a clinical syndrome that is often not recognized and, therefore, not treated appropriately. The presence of delirium is a predictor of increased morbidity and mortality, longer hospitalization, and more likely discharge to a nursing facility. This article reviews the pathophysiology, etiology, diagnosis, and treatment of delirium in the palliative medicine population.

A pilot study of palliative medicine fellows' hospice home visits.

This was a prospective descriptive study of hospice physician home visits (HVs) conducted by Hospice and Palliative Medicine Fellows. Our objectives were 1) to improve our knowledge of hospice care at home by describing physician HVs 2) to identify the indications for physician HVs and the problems addressed during the HV. Data was collected on 58 consecutive patients using a standardized form completed before and after the home visit. More than half of the persons were women. Most were Caucasian. Median age was 75 years; 57% had cancer; 77% were do-not-resuscitate. 76% HV occurred in the home. The median visit duration was 60 minutes; median travel distance and time 25 miles and 42 minutes, respectively. A hospice nurse case manager was present in 95%. The most common issues addressed during HVs were: health education, symptom management, and psychosocial support. Medication review was prominent. Physicians identified previously unreported issues. Symptom control was usually pain, although 27 symptoms were identified. Medications were important; all home visits included drug review and two thirds drug change. Physicians had unique responsibilities and identified important issues in the HV. Physicians provided both education and symptom management. Physician HVs are an important intervention. HVs were important in continuity of care, however, time-consuming, and incurred considerable travel, and professional time and costs.

Palliative medicine fellowship: a study of resident choices.

CONTEXT: There are no data on the motives or characteristics of physicians choosing fellowship training in Hospice and Palliative Medicine (HPM). OBJECTIVES: To understand more about the residents who choose HPM and what leads them to this decision. METHODS: An electronic survey of HPM fellows initiating training in July 2009. RESULTS: Seventy-six physicians began the study, with 62 responders (82%) completing all questions. Fifty-five percent were aged 30-40 years, and 61% were female. Sixty-eight percent were non-Hispanic Caucasian, 24% were Asian, and none were African American. Fifty-five percent were trained in internal medicine. Most (86%) asserted that the care of a dying, critically ill, or symptomatic person impacted their decision to enter the field of HPM. Sixty-three percent did not feel prepared to manage dying patients, and 41% felt personal regret about the care they delivered. The major reasons for choosing the specialty were a desire to contribute to relief of suffering (79%), enhance end-of-life care (73%), and improve communication (78%). Ninety-five percent received negative comments about their career choice. Fifty-nine percent had no exposure to hospice or palliative medicine in medical school, whereas 61% had an exposure available during residency. Forty-seven percent decided to enter a fellowship in the third year of residency, and 33% applied after practicing in their primary specialty for a median of 10 years. Accreditation, strength of education, and a hospital palliative medicine service were required by the majority for selection of a fellowship program. CONCLUSION: Negative experiences with end-of-life care in residency, particularly in the intensive care unit, continue to be a factor in selection of HPM as a specialty. Many residents make their decision to enter the field and apply during Postgraduate Year 3. Most received negative comments about the choice. Fellows require a broad range of experience when selecting a fellowship program.

Physician home visits by palliative medicine fellow.

BACKGROUND: Physician home visits (HVs) are an important model of care for the terminally ill. Hospice and palliative medicine (HPM) fellows make a minimum of 25 HVs. OBJECTIVE: To describe HPM fellow hospice HVs in an academic palliative medicine practice. METHODS: Retrospective chart review of HVs conducted by 1 HPM fellow. RESULTS: Twenty-five HVs were made to 21 hospice patients. Nineteen had advanced cancer. Indications for visits were symptom management (22) and education (21). On average 2.8 symptoms (± SD 1) were addressed on each visit, usually pain. Medications were reviewed at every visit. CONCLUSIONS: HVs are an important part for patient care and fellow education, which provided an opportunity for medication revision and symptom education.

Modern management of malignant hypercalcemia.

Hypercalcemia occurs in 10% to 20% of those with advanced cancer. It is considered an oncologic emergency. Presenting symptoms include common gastrointestinal symptoms that may be difficult to differentiate from tumor or treatment-related symptoms. These include nausea, vomiting, and constipation. As levels increase or if development is rapid, neuropsychiatric symptoms such as delirium can develop. Untreated it will lead to coma and death. Current preferred therapies are the bisphosphonate agents, zoledronate and pamidronate with saline rehydration.

The business of palliative medicine--part 6: clinical operations in a comprehensive integrated program.

The medical care of individuals with advanced disease is complex and has historically been fragmented and suboptimal. Palliative medicine attempts to address these needs. The Harry R. Horvitz Center for Palliative Medicine at the Cleveland Clinic is an established comprehensive integrated program. Structured and seamless clinical operations are important to ensure the best delivery of high-quality medical care and continuity for those affected by life-limiting illness.

Comfort measures: practical care of the dying cancer patient.

Most patients with advanced malignancy will die of their disease. Care of the dying is therefore a fundamental skill for the oncologist. Although protocols exist in other countries, there is no established protocol in the United States. We present a protocol for management of the dying that is clinically useful and review the existing evidence-base.

Scopolamine for cancer-related nausea and vomiting.

Nausea and vomiting is a common and troublesome symptom in advanced cancer. There have been different approaches described for the management of nausea and vomiting, specifically empirical and etiological. Scopolamine is listed in textbooks as a useful medication in management of nausea and vomiting in this setting, although there is no published data to support this recommendation. We present three cases that support the use of scopolamine in an etiologically based approach for management of nausea in advanced cancer.

Errors in opioid prescribing: a prospective survey in cancer pain.

CONTEXT: Cancer pain is debilitating and has multidimensional consequences. It can be treated adequately in up to 90% of patients by following pain management guidelines. Nevertheless, inadequate pain control remains a global problem. OBJECTIVES: We surveyed prescribing patterns in patients referred to our Palliative Medicine Program (PMP) to identify common errors in opioid use. METHODS: Consecutive cancer patients seen by our PMP were prospectively surveyed for the presence of pain and errors in opioid prescribing at the time of initial consultation. Our recommendations to correct and optimize pain management also were recorded. RESULTS: One hundred eighty-six consecutive cancer patients were screened. One hundred seventeen (63%) had cancer pain, 151 opioid prescribing errors were detected, and 147 different recommendations were made. Most common were failure to order around-the-clock opioids for constant pain, and the failure to treat or prevent opioid side effects. Multiple errors were more common in females, but the sex difference did not reach statistical significance. There was no difference in the errors by pain severity or reason for consultation. CONCLUSION: Opioid prescribing errors were common. Females may be at greater risk of multiple errors. A PM consultation program is effective in identifying and correcting a wide variety of opioid prescribing errors.

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.

A comparative study of 2 sustained-release morphine preparations for pain in advanced cancer.

PURPOSE: Several sustained-release morphine (SRM) formulations are available internationally. This study compared 2 such products available in the United States, SR1 and SR2. PATIENTS AND METHODS: In an open-label study, patients with advanced cancer pain were randomized to receive SR1 or SR2 every 12 hours around-the-clock (ATC) for 5 days, with immediate release (IR) liquid morphine for rescue dosing (RD). Efficacy, safety, and patient acceptability were determined. RESULTS: A total of 32 patients were evaluable for efficacy and toxicity. Pain scores, RD dosage, RD frequency over 5 days, RD within 3 hours before and after the scheduled SRM, and 8 of the 11 evaluated side effects were higher in the SR1 group. At presumed morphine steady state (day 3), pain scores (P = .05), RD dosage (P = .07), RD frequency (P = .07), and number of RD +/-3 hours from scheduled SRM dose (P = .05) were consistently greater in the SR1 group (despite a higher median morphine dose in that group). There was a clinically important and directionally consistent trend that favored SR2, although not all were statistically significant. Patient preference favored SR2 (P < .05). Neither group had difficulty swallowing SR1 or SR2. CONCLUSIONS: This is the first study that directly compared two 12-hour SRM formulations. The data suggested, by multiple clinically important measures, that SR2 may provide superior analgesic efficacy and less toxicity compared to SR1. It also supports the concept that it cannot be assumed that different SR formulations of a given opioid are clinically equivalent. A larger study is needed to confirm our findings.

Validation of a simplified anorexia questionnaire.

CONTEXT: Anorexia is a common symptom in cancer and is usually assessed by multiple questions and multidimensional questionnaires. A simplified questionnaire would be less burdensome to patients and abbreviate the process. OBJECTIVES: We compared the reliability at one point in time, sensitivity to change over time, and prognostic accuracy of a two-item questionnaire with the Functional Assessment of Anorexia and Cachexia Therapy shortened 12-question version (A/CS-12). METHODS: Individuals with cancer, who were cognitively intact and verbally agreed to participate, completed a two-item questionnaire and A/CS-12 in random order and again seven days later. We compared the direction of response to the summated two-item questionnaire to the validated A/CS-12 score at a single point in time, then intra-patient changes over a seven-day period of time. Scores of both questionnaires were divided into poor, moderate and good appetite and compared to survival using Kaplan-Meyer curves. Bootstrapping was used to construct confidence intervals for estimated probability agreement. Survival analysis also used hazard ratios from a Cox Proportional Hazards model. RESULTS: One hundred seventeen individuals from a single institution participated, who were either admitted to an inpatient palliative unit or seen in an outpatient/palliative medicine unit. Median age was 58.8 (range 10.7-87.1 years). Agreement at one point in time was 0.64 (95% confidence interval [CI] 0.63 - 0.66). Agreement over time was 0.53 (CI 0.41 - 0.64). The A/CS-12 predicted survival based on scores on Days 1 and 7 (P<0.001), (P=0.003) (HR 0.97 day 1, HR 0.95 day 7), whereas the simplified questionnaire failed to predict survival. CONCLUSIONS: A simplified questionnaire has moderate correlation with the A/CS-12 at one point in time but loses sensitivity over time, and lacks the ability to predict survival. A change in the questionnaire may improve reliability. Changing question 2 of the simplified questionnaire to a neutral form (better, same or worse appetite) may improve sensitivity and prognostic capability.

Cancer-related fatigue: central or peripheral?

To evaluate cancer-related fatigue (CRF) by objective measurements to determine if CRF is a more centrally or peripherally mediated disorder, cancer patients and matched noncancer controls completed a Brief Fatigue Inventory (BFI) and underwent neuromuscular testing. Cancer patients had fatigue measured by the BFI, were off chemotherapy and radiation (for more than four weeks), had a hemoglobin level higher than 10 g/dL, and were neither receiving antidepressants nor were depressed on a screening question. The controls were screened for depression and matched by age, gender, and body mass index. Neuromuscular testing involved a sustained submaximal elbow flexion contraction (SC) at 30% maximal level (30% maximum elbow flexion force). Endurance time (ET) was measured from the beginning of the SC to the time when participants could not maintain the SC. Evoked twitch force (TF), a measure of muscle fatigue, and compound action potential (M-wave), an assessment of neuromuscular-junction transmission were performed during the SC. Compared with controls, the CRF group had a higher BFI score (P<0.001), a shorter ET (P<0.001), and a greater TF with the SC (CRF>controls, P<0.05). This indicated less muscle fatigue. There was a greater TF (P<0.05) at the end of the SC, indicating greater central fatigue, in the CRF group, which failed to recruit muscle (to continue the SC), as well as the controls. M-Wave amplitude was lower in the CRF group than in the controls (P<0.01), indicating impaired neuromuscular junction conduction with CRF unrelated to central fatigue (M-wave amplitude did not change with SC). These data demonstrate that CRF patients exhibited greater central fatigue, indicated by shorter ET and less voluntary muscle recruitment during an SC relative to controls.

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.