Susan B. LeGrand

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.

Methylphenidate for fatigue in advanced cancer: a prospective open-label pilot study.

Psychostimulants such as methylphenidate are used for fatigue in cancer patients. We report a prospective, open-label, pilot study of the successful use of methylphenidate to treat fatigue in nine of 11 consecutive patients with advanced cancer. Seven had received radiation or chemotherapy, a median of three weeks (range from one to 30 weeks) prior to methylphenidate. A rapid onset of benefit was noted, even in the presence of mild anemia. Sedation and pain also improved in some. Only one patient had side effects severe enough to stop the medication.

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.

Normal-release and controlled-release oxycodone: pharmacokinetics, pharmacodynamics, and controversy.

Abstract. Oxycodone has become one of the most popular opioids in the United States. It is superior to morphine in oral absorption and bioavailability, and similar in terms of protein binding and lipophilicity. Gender more than age influences oxycodone elimination. Unlike morphine, oxycodone is metabolized by the cytochrome isoenzyme CYP2D6, which is severely impaired by liver dysfunction. Controlled-release (CR) oxycodone has become one of the most frequently utilized sustained-release opioids in the United States. Both its analgesic benefits and its side effects are similar to those of CR morphine. CR oxycodone is similar to morphine and other opioids in its abuse potential. Deaths attributable to oxycodone are usually associated with polysubstance abuse in which oxycodone is combined with psychostimulants, other opioids, benzodiazepines or alcohol. Oxycodones kappa receptor binding has little role in abuse or addiction. The cost of CR oxycodone is prohibitive for most American hospices.

A phase II study of methylphenidate for depression in advanced cancer

This study evaluated the use of methylphenidate for depression in advanced cancer. Design: Phase II open-label prospective study. Eligibility criteria: No previous use of methylphenidate or current use of other antidepressants. Evaluation: Depression and response to treatment were determined by asking the patient: “are you depressed?” Patients were assessed at baseline and at days 3, 5, and 7. Treatment: Starting dose was 5 mg at 8:00 a.m. and 12:00 noon. The dose was titrated for lack of response on any of the assessment days. Response criteria: A negative response to the question: “are you depressed?” Results: Some 41 patients were enrolled and 30 (15 men, 15 women) completed the study. Median age was 68 years (range: 30-90). Methylphenidate was stopped for six patients because of side effects and five were not evaluable; 21 responded to 10 mg/day on day 3; the other nine responded to 20 mg/day on day 5; 29 maintained their positive response through day 7. Anorexia, fatigue, concentration, and sedation also improved in some. All who completed the study had tolerable side effects, none of which caused treatment to stop. Conclusions: Methylphenidate is effective for depression in advanced cancer. A starting dose of 10 mg in divided doses is effective in most patients. Dose escalation may be needed. Improvement occurs within three days. Close monitoring of side effects is recommended.

The clinical effects of music therapy in palliative medicine

GoalThis study was to objectively assess the effect of music therapy on patients with advanced disease.Patients and methodsTwo hundred patients with chronic and/or advanced illnesses were prospectively evaluated. The effects of music therapy on these patients are reported. Visual analog scales, the Happy/Sad Faces Assessment Tool, and a behavior scale recorded pre- and post-music therapy scores on standardized data collection forms. A computerized database was used to collect and analyze the data.ResultsUtilizing the Wilcoxon signed rank test and a paired t test, music therapy improved anxiety, body movement, facial expression, mood, pain, shortness of breath, and verbalizations. Sessions with family members were also evaluated, and music therapy improved families’ facial expressions, mood, and verbalizations. All improvements were statistically significant (P<0.001). Most patients and families had a positive subjective and objective response to music therapy. Objective data were obtained for a large number of patients with advanced disease.ConclusionsThis is a significant addition to the quantitative literature on music therapy in this unique patient population. Our results suggest that music therapy is invaluable in palliative medicine.

Controversies in pharmacotherapy of pain management

Since the establishment of the WHO three-step ladder for management of cancer pain, several controversies have arisen, which are partly due to new drug development, reformulations of older analgesics, and technological advancements. As a result, clinicians need clarification of several questions. Is morphine the opioid of choice for moderate to severe pain in cancer? Should combinations of opioids be used? When should spinal opioids be used to treat pain in cancer? What are the appropriate opioid doses for breakthrough pain? Should selective cyclo-oxygenase (COX) 2 inhibitors be used? What is the best tactic to treat neuropathic pain, and what first-line adjuvant analgesic should be used? And do bisphosphonates relieve bone pain in cancers other than breast cancer and myeloma? This review addresses these questions.

Promoting excellence in end‐of‐life care in ALS

The type and quality of end‐of‐life care varies greatly in ALS; the time to initiate end‐of‐life care is not defined, and decision making is hampered by logistical and financial barriers. There has been no systematic review of these issues in ALS. The goals of this initiative are to: 1) improve end‐of‐life care for patients with ALS and families based on what limited evidence is available; 2) increase awareness, interest, and debate on the end‐of‐life care in ALS; and 3) identify areas needed for new prospective clinical research. The ALS Peer Workgroup reviewed the literature and 1) identified the current state of knowledge, 2) analysed the gaps in care, and 3) provided recommendations for standard of care and future research. It was shown that areas of investigation are needed on the incorporation of an interdisciplinary approach to care in ALS that includes: psychosocial evaluation and spiritual care; the use of validated instruments to assess patient and caregiver quality of life; and the establishment of proactive caregiver programs. Several public policy changes that will improve coverage for medical care, hospice, and caregiver costs are also reviewed. More clinical evidence is needed on how to provide optimal end‐of‐life care specifically in ALS.

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.

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.