Methylnaltrexone for opioid-induced constipation in advanced illness.

BACKGROUND: Constipation is a distressing side effect of opioid treatment. As a quaternary amine, methylnaltrexone, a mu-opioid-receptor antagonist, has restricted ability to cross the blood-brain barrier. We investigated the safety and efficacy of subcutaneous methylnaltrexone for treating opioid-induced constipation in patients with advanced illness. METHODS: A total of 133 patients who had received opioids for 2 or more weeks and who had received stable doses of opioids and laxatives for 3 or more days without relief of opioid-induced constipation were randomly assigned to receive subcutaneous methylnaltrexone (at a dose of 0.15 mg per kilogram of body weight) or placebo every other day for 2 weeks. Coprimary outcomes were laxation (defecation) within 4 hours after the first dose of the study drug and laxation within 4 hours after two or more of the first four doses. Patients who completed this phase were eligible to enter a 3-month, open-label extension trial. RESULTS: In the methylnaltrexone group, 48% of patients had laxation within 4 hours after the first study dose, as compared with 15% in the placebo group, and 52% had laxation without the use of a rescue laxative within 4 hours after two or more of the first four doses, as compared with 8% in the placebo group (P<0.001 for both comparisons). The response rate remained consistent throughout the extension trial. The median time to laxation was significantly shorter in the methylnaltrexone group than in the placebo group. Evidence of withdrawal mediated by central nervous system opioid receptors or changes in pain scores was not observed. Abdominal pain and flatulence were the most common adverse events. CONCLUSIONS: Subcutaneous methylnaltrexone rapidly induced laxation in patients with advanced illness and opioid-induced constipation. Treatment did not appear to affect central analgesia or precipitate opioid withdrawal. (Clinical Trials.gov number, NCT00402038 [ClinicalTrials.gov].).

Trajectory of medication-induced constipation in patients with cancer.

PURPOSE/OBJECTIVES: To determine the severity and trajectory of constipation among patients with cancer from opioids and/or vinca alkaloids. DESIGN: Exploratory, descriptive. SETTING: Moffitt Cancer Center, a National Cancer Institute-designated comprehensive cancer center in Tampa, FL. SAMPLE: 400 patients at risk for developing medication-induced constipation from opioids, vinca alkaloids, or both. METHODS: Patients' baseline data included the Constipation Assessment Scale (CAS), the constipation item from the Memorial Symptom Assessment Scale (MSAS) for intensity and distress, and the laxative interview. Following the interview, the medical chart was reviewed for clinical and demographic data. Patients were asked about constipation (CAS) and laxatives consumed (laxative interview) during eight weekly telephone calls. MAIN RESEARCH VARIABLES: Constipation presence, intensity, and distress. FINDINGS: At baseline, 63% of patients reported some level of constipation. During the eight weeks, constipation fluctuated with scores ranging from 0-16, with the opioid-only group showing a small but statistically significant decrease in intensity. Constipation intensity and distress on the MSAS were significantly correlated (r = 0.76; p = 0.000). CONCLUSIONS: The majority of the sample reported constipation that ranged from mild to severe, persisted over time, and caused symptom distress. Therefore, healthcare providers in the cancer center likely were neither adequately managing the medication-induced constipation nor apparently teaching patients to manage it themselves. IMPLICATIONS FOR NURSING: National Comprehensive Cancer Network guidelines support the importance of managing medication-induced constipation. However, guidelines are not being followed in many cases; therefore, more focus is needed on constipation in clinical and educational settings as well as more research. KNOWLEDGE TRANSLATION: Patients receiving opioids and vinca alkaloids are at risk of constipation. Currently, medication-induced constipation is poorly managed. Managing constipation may lessen symptom distress, thereby improving quality of life in these patients.

Therapy choices and quality of life in young breast cancer survivors: a short-term follow-up.

BACKGROUND: Premenopausal women represent approximately 35% of new breast cancer diagnoses. Diagnosis and treatment may lead to substantial disruption in quality of life (QOL). METHODS: Premenopausal patients (aged 18 to 50 years) treated for nonmetastatic breast cancer completed a mailed questionnaire. Multiple self-reported QOL measures and clinical data were collected. Cluster analysis and Cronbach's α were used to validate the survey. Analysis of variance was performed for specific interventions. Lower interference scores conveyed higher QOL. RESULTS: The response rate was 49.8%. Cronbach's α was 0.96. Immediate contralateral prophylactic mastectomy (CPM) carried the highest interference (mean, 3.3148) with sexuality compared with no CPM (mean, 2.85) or delayed CPM (P = .03). Breast conservation had the least interference with appearance (P < .01) and work and finances (P = .02). CONCLUSIONS: Therapeutic mastectomy and CPM with or without reconstruction may adversely affect QOL. These findings suggest that the choice and timing of interventions may significantly affect patient satisfaction.

Methylnaltrexone for opioid-induced constipation in patients with advanced illness: a 3-month open-label treatment extension study.

Methylnaltrexone is a methylated form of the mu-opioid antagonist naltrexone that blocks peripheral effects of opioids without affecting centrally mediated analgesia. The authors conducted a 3-month open-label extension trial of methylnaltrexone in patients with advanced illness and opioid-induced constipation (OIC). Following completion of a 2-week double-blind (DB) trial, 82 patients with OIC who did not respond to laxatives received subcutaneous (SC) methylnaltrexone as needed for up to 3 months. Patients received 0.15 mg/kg as a first dose, adjusted to 0.3 mg/kg or 0.075 mg/kg as needed (maximum of one dose per 24 hours). Mean laxation response (rescue-free bowel movement within 4 hours) rates (DB phase, months 1, 2, 3 open-label phase) were 45.3%, 45.5%, 57.7%, and 57.3%, respectively, for patients treated with DB methylnaltrexone and 10.8%, 48.3%, 47.6%, and 52.1%, respectively, for patients treated with DB placebo. Median time to laxation among responders was 45 minutes (range 0-4 hours) for all doses. Approximately 50% of patients reported improvement in constipation distress. Patient and investigator global clinical impression of change scores also improved. There were minimal changes in pain scores and opioid withdrawal symptoms. Adverse events included abdominal pain and nausea, mostly mild or moderate in severity. SC methylnaltrexone administered PRN (as needed) for up to 3 months continued to rapidly induce laxation in advanced illness patients with OIC.

Varenicline effects on craving, cue reactivity, and smoking reward.

RATIONALE: Varenicline is an α4ß2 nicotinic acetylcholine receptor partial agonist that has been found to be effective for treating tobacco dependence. However, the subjective and behavioral mediators of its efficacy are not known. OBJECTIVES: Using multiple sessions of laboratory-based assessment, this double-blind, placebo-controlled experiment was designed to test if varenicline reduced both tonic and cue-provoked tobacco cravings, and if it attenuated perceived reward from smoking. METHODS: Participants in the present analysis include 100 smokers who were scheduled for three assessment sessions: at baseline, before receiving medication; at mid-run-in, 5-7 days after beginning medication; and after full dosage was reached, 12-15 days. Following overnight abstinence, each session included assessment of tonic craving, reactivity (including craving) to smoking cues, expected value of a cigarette, smoking behavior, and self-reported reward following smoking. RESULTS: Varenicline, compared to placebo, reduced tonic craving, cue-provoked craving by the final assessment, the expected value of cigarettes, number of puffs and time spent smoking, and self-reported reward (i.e., satisfaction) from smoking. CONCLUSIONS: Results showing that varenicline reduced tonic craving levels and perceived reward from smoking are consistent with reports from clinical trials, strengthening the evidence in support of these subjective mechanisms of action. This is the first placebo-controlled study to demonstrate that varenicline reduced cue-provoked cravings, thereby offering another potential mediator of its therapeutic effects. Findings may aid in the development of more targeted interventions for tobacco dependence.

Advanced care planning--empowering patients for a peaceful death.

In the early 1900's, Americans had a life expectancy of about 50 years. Childhood mortality was very high and an adult who lived into their sixties was considered to be doing pretty well. Prior to the advent of different types of antibiotics, people would die quickly of infectious disease or accidents and medicine only really focused on caring and comfort. Since then, there has been a shift in medicines focus. New science, technology and communications have shifted the way Americans treat incurable diseases and have promoted the idea of aggressive fighting as well as to keep patients alive at any costs. The internet has allowed easy access for patients to do on-line research and to know the treatments for diseases and the availability of trials. This has promoted the idea that every disease or cancer is curable if the patient does exactly as the internet says. It has hindered the idea of compassionate care and dying with dignity so that a patient can stay alive at all costs, even in a vegetative state. In the last two decades, there has been a significant expansion of palliative and supportive care services in the United States. This has including the development of a specialty for palliative care medicine with a board certification in hospice and palliative medicine. A challenge to the field has been the reluctance of physicians to request palliative care consults in a very timely manner as well as relinquish care of their patients. A common occurrence in the United States, at many cancer centers, is the treatment of chemotherapy and radiation up until the day before a patient dies. At this point, the physician ends up throwing up his or her hands with nothing left to offer the patient or its family. However, what we have been finding is that presently there are now many oncologists who are willing to refer patients to palliative care for specific management of difficult pain control issues. At the Moffitt Cancer Center, we have a Palliative Care consulting service along with a Palliative Care Fellowship program where we work with cancer teams to provide resources to them when they are running into difficulties with their patients. Typically, we step in when first line treatments have failed, symptoms have shown no signs of decrease, or when the primary teams have exhausted their standard management options. Our hope is for the primary care teams to be able to manage basic symptoms themselves and only call on the Palliative Care team when they have surpassed their comfort zone. For example, the Palliative Care team would step in if a patients dosage of medication was out of a primary teams spectrum. Other uses of the Palliative Care team include having the end of life discussion with the patients to find out what their expectations are of their treatment, what their concerns are and what their requests are. Normally treating primary teams are very uncomfortable in having this discussion with their patients due to the feeling that they are giving up hope or the fact that they are letting patients know that the end of the road is near. The Palliative Care team can then be called upon to come in and transfer the care from the primary team to the "death team". At Moffitt we have instituted a number of strategies to make this transition acceptable and more beneficial for the patients. One of the strategies that we used is an Advanced Care Plan. By having a consultation at the time when the patient is diagnosed, we are able to speak with them about what it is that they see in terms of what would be acceptable to them. We use the Project Grace Advance Care Plan which was developed by a physician and is very simple to understand. With this tool, we are able to bring up the discussion while trying to focus in on the patients spirituality and the coping mechanism as the cancer patient. This allows the conversation of end of life treatment preferences and what the patients typical desire is for life sustaining measures.