Abstract
Moselli NM, Cruto M, Massucco P, et al. Long-term continuous subcutaneous infusion of ketoprofen combined with morphine: A safe and effective approach to cancer pain. Clin J Pain 2010;26:267–274.
International guidelines for the management of cancer pain recommend opioids and non-steroidal anti-inflammatories (NSAIDs) as the cornerstone of therapy. However, as disease advances, many patients become unable to take oral medications, thus alternative routes of administration are utilized. In this prospective, observational, open-label pilot study, the authors attempted to evaluate the feasibility, safety, and efficacy of ketoprofen combined with opioids in a long-term continuous subcutaneous infusion (CSI) for cancer pain. The authors added ketoprofen to a morphine CSI in 172 consecutive patients (study group, SG). Concomitantly, 48 patients received opioid CSIs without ketoprofen for contraindications to NSAIDs (control group, CG). Safety was evaluated according to the number of adverse events and their severity. The measures of efficacy were pain relief (NRS, Numerical Rating Scale), percentage of patients that needed to increase their morphine dosage, and median relative increase between weeks 2 and 4. Results demonstrated that toxicity typically attributable to NSAIDs was recorded in 4.1% of patients after 3 months of treatment and the combination of NSAIDs and corticosteroids did not seem not to influence the risk of adverse gastrointestinal effects. The local side effects related to the CSI regimen were negligible in both groups. By the fourth week, pain was well controlled (NRS 0 to 2) in 80% of patients receiving ketoprofen compared with 46% of patients without ketoprofen (p < 0.01.) Moreover, the percentage of patients needing to increase the morphine dosage (40.5% vs. 68.7%, p < 0.01) and the relative dose increase (12% vs. 25%, p < 0.005) were significantly lower in the SG. The authors conclude that a ketoprofen CSI in combination with opioids is a feasible, safe, and effective approach to cancer pain.
Higginson IJ, Evans CJ. What is the evidence that palliative care teams improve outcomes for cancer patients and their families? Cancer J 2010;16:423–435.
Patients with advanced cancer experience a complex maze of problems. Palliative care services have developed to meet the needs of these patients, but the effectiveness of these teams should be considered. The authors attempted to determine whether palliative care teams achieve their aims and improve outcomes for patients with advanced cancer and their caregivers, in terms of improving symptoms and quality of life and/or reducing the emotional concerns of family caregivers. The authors conducted a systematic review, searching standard databases augmented by reference lists of earlier reviews. The review focused on specialist (i.e., with trained and dedicated professionals) palliative care in the home, hospital, or designated inpatient settings for patients with cancer. Outcomes were pain, symptoms, quality of life, use of hospital services, and anxiety. Studies were excluded if they did not test specialist palliative care services. Eight randomized controlled trials and 32 observational or quasi-experimental studies were identified. Evidence demonstrated that home, hospital, and inpatient specialist palliative care significantly improved patient outcomes in the domains of pain and symptom control, anxiety, and reduced hospital admissions, and suggests that specialist palliative care should be part of care for cancer patients. The authors do note that although the appraisal of evidence found improvements across domains, there is a need to understand better the effects of different models of palliative care and to use standardized outcome measurements.
Moraska AR, Sood A, Sloan JA, et al. Phase III, randomized, double-blind, placebo-controlled study of long-acting methylphenidate for cancer-related fatigue: North Central Cancer Treatment Group NCCTG-N05C7 trial. J Clin Oncol 2010;28:3673–3679.
Fatigue is one of the most common symptoms experienced by patients with cancer, at times more prevalent than pain, and oftentimes more disabling than pain. The authors of this phase III, randomized, double-blind, placebo-controlled study attempted to evaluate the efficacy of long-acting methylphenidate for improving cancer-related fatigue in 148 patients and to also assess its toxicities. The authors randomly assigned adult cancer patients to receive methylphenidate (target dose, 54 mg/d) or placebo for 4 weeks. The Brief Fatigue Inventory was utilized as the primary outcome measure, whereas secondary outcome measures included a Symptom Experience Diary (SED), the Short Form-36 (SF-36) Vitality Subscale, a linear analog self-assessment, the Pittsburgh Sleep Quality Index, and the Subject Global Impression of Change. Results demonstrated that using an area under the serum concentration-time curve analysis, there was no evidence that methylphenidate (when compared with placebo) improved the primary endpoint of cancer-related fatigue in this patient population (p = 0.35). Comparisons of secondary endpoints, including clinically significant changes in quality-of-life variables and cancer-related fatigue change from baseline, were similarly negative. However, a subset analysis suggested that patients with more severe fatigue and/or with more advanced disease did have some fatigue improvement with methylphenidate (e.g., in patients with stage III or IV disease). There was a significant difference in self-reported toxicities (SED), with increased levels of nervousness and appetite loss in the methylphenidate arm. The authors conclude that in this clinical trial they were unable to support the primary pre-study hypothesis that long-acting methylphenidate would decrease cancer-related fatigue.
Lennernas B, Frank-Lissbrant I, Lennernas H, et al. Sublingual administration of fentanyl to cancer patients is an effective treatment for breakthrough pain: Results from a randomized phase II study. Palliat Med 2010;24:286–293.
The treatment of breakthrough pain (BTP) is at times woefully inadequate. In this interesting study, the authors evaluated the efficacy and tolerability of sublingual fentanyl (SLF) for BTP in adult opioid-tolerant cancer patients. Patients received one dose of placebo, SLF 100, 200, and 400 μg in random order at four pain episodes. The primary efficacy endpoint was pain intensity difference (PID) from baseline. Twenty-seven patients received study medication, and overall, PID increased significantly with SLF 400 μg versus placebo (8.57 mm, p < 0.0001). Improvements were statistically different from placebo at 15 minutes (p = 0.005). SLF 100 and 200 μg showed a numerical trend toward improved pain relief. A dose that gave a clinically important reduction in pain (PID > 20 mm) was identified by 95% of patients. Reduced use of rescue medication (p < 0.001, SLF 400 μg) and improved global assessment of treatment (p = 0.0146, SLF 400 μg) confirmed these differences as clinically important and significant. Of treatment-related adverse effects, nausea and dizziness were the most common. The authors conclude that SLF appears to be a fast, effective, and well-tolerated treatment for BTP.
Doug M, Adi Y, Williams J, et al. Transition to adult services for children and young people with palliative care needs: A systematic review. Arch Dis Child 2011;96:78–84.
In this article, the authors attempted to evaluate the evidence on the transition process from child to adult services for young people with palliative care needs utilizing a systematic review. Young people between the ages of 13 and 24 years with palliative care conditions in the process of transition were primary targets of this review, with main outcome measures including young people and their families' experiences of transition, the process of transition between services, and its impact on continuity of care and models of good practice. Ninety-two studies were included. Results demonstrated that articles on transition services were of variable quality when applied to palliative care contexts, with most focusing on common life-threatening and life-limiting conditions. No standardized transition programs were identified, and most guidelines used to develop transition services were not evidence-based. Moreover, most studies on transition programs were predominantly condition-specific (e.g., cystic fibrosis (CF) services. CF services offered high-quality transition with the most robust empirical evaluation. There were differing condition-dependent viewpoints on when transition should occur, but agreement on major principles guiding transition planning and probable barriers were noted. There was evidence of poor continuity between child and adult providers, with most originating from within child settings. The authors conclude that palliative care was not, in itself, a useful concept for locating transition-related evidence. It is not possible to evaluate the merits of the various transition models for palliative care contexts, or their effects on continuity of care, as there are no long-term outcome data to measure their effectiveness. Use of validated outcome measures would facilitate research and service development.