Abstract
Ad VB, Weinstein G, Dutta PR, et al.: Gabapentin for the treatment of pain syndrome related to radiation-induced mucositis in patients with head and neck cancer treated with concurrent chemoradiotherapy. Cancer 2010;116:4206–4213.
In this retrospective study, the authors attempted to evaluate the efficacy of gabapentin for the treatment of pain syndromes related to radiation-induced muscositis in patients with head and neck cancer receiving concurrent chemoradiotherapy. Data from 42 patients were analyzed. Gabapentin was initiated in the second week of radiotherapy, with opioids prescribed in addition to gabapentin to obtain adequate pain control. Results demonstrated that at a median dose of 2700 mg of gabapentin per day, only 33% and 55% of patients required additional low-dose opioid medications for pain control during the third and fourth week of treatment respectively, despite exhibiting a grade 2 or higher mucositis in 71% and 86% of patients respectively. In addition, during the last weeks of treatment, 71% of patients required additional low-dose opioids for adequate pain control, despite the presence of grade 2 or higher muscositis in 95% and 100% of patients at weeks 5 and 6 respectively. The authors conclude that gabapentin appears to be a promising agent in reducing the need for high doses of opioids and avoiding treatment interruptions in patients with head and neck cancers treated with concurrent chemoradiotherapy, and warrants further evaluation in controlled studies.
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.
According to numerous guidelines, nonsteroidal anti-inflammatories (NSAIDs) and opioids are the mainstay of treatment of cancer pain. In many episodes of cancer pain, alternative routes of administration are needed, and NSAIDs are usually abandoned when such a situation arises. 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. In 172 consecutive patients, ketoprofen was added to a morphine CSI (study group); concomitantly, 48 patients received an opioid CSI without ketoprofen (control group). The CSI was delivered through a single-use elastomeric pump that was refilled weekly, and safety was evaluated according to the number of adverse events and their severity. The measures of efficacy were pain relief (Numerical Rating Scale, NRS), percentage of patients that needed to increase morphine dosage, and median relative increase between weeks 2 and 4. Results demonstrated that toxicity typically attributable to NSAIDs were recorded in 4.1% of patients after 3 months of treatment and the combination of NSAIDs and corticosteroids did not seem to influence the risk of gastrointestinal adverse effects. The local side effects related to the CSI regimen were negligible in both the 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 study group. The authors conclude that a ketoprofen CSI in combination with opioids is a feasible, safe, and effective approach to cancer pain.
Simon ST, Higginson IJ, Booth S, et al.: Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Database Syst Rev 2010 20;1:CD007354.
Breathlessness is one of the most distressing symptoms in the advanced stages of both malignant and non-malignant disease. Benzodiazepines have been widely used for the treatment of breathlessness and recommended in the palliative literature, even though evidence for such recommendations is unclear. The intent of this Cochrane review was to determine the efficacy of benzodiazepines for the relief of breathlessness in advanced disease. Fourteen electronic databases up to September 2009 were searched; reference lists of all relevant studies, key textbooks, reviews, and Web sites were checked, and investigators and specialists in palliative care were contacted for unpublished data. Criteria for inclusion in this review included randomized controlled trials (RCTs) and controlled clinical trials (CCTs) assessing the effect of benzodiazepines in relieving breathlessness in patients with advanced stages of cancer, chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF), motor neuron disease (MND), and idiopathic pulmonary fibrosis (IPF). Results demonstrated that seven studies were identified, including 200 analyzed participants with advanced cancer and COPD. Analysis of all seven studies (including a meta-analysis of six out of seven studies) did not show a beneficial effect of benzodiazepines for the relief of breathlessness in patients with advanced cancer and COPD. Furthermore, no significant effect could be observed in the prevention of breakthrough dyspnea in cancer patients. Sensitivity analysis demonstrated no significant differences regarding type of benzodiazepine, dose, route, and frequency of delivery, duration of treatment, or type of control. The authors conclude that there is no evidence for a beneficial effect of benzodiazepines for the relief of breathlessness in patients with advanced cancer and COPD, although there was a slight but non-significant trend toward a beneficial but the overall effect size is small. The authors suggest that these results justify considering benzodiazepines as a second or third-line treatment within an individual therapeutic trial, when opioids and non-pharmacological measures have failed to control breathlessness.
Detering KM, Hancock AD, Reade MC, Silvester W: The impact of advance care planning on end of life care in elderly patients: Randomised controlled trial. BMJ 2010;340:1345.
Advance care planning remains a goal to ensure honoring all patients wishes, particularly in elderly patients. In the prospective randomized controlled trial, completed in a university hospital in Melbourne, Australia, the authors attempted to investigate the impact of advance care planning on end-of-life care in elderly patients. A total of 309 legally competent medical inpatients aged ≥80 were followed for 6 months or until death. Participants were randomized to receive usual care or usual care plus facilitated advance care planning. Advance care planning aimed to assist patients to reflect on their goals, values, and beliefs; to consider future medical treatment preferences; to appoint a surrogate; and to document their wishes. Results demonstrated that 154 of the 309 patients were randomized to advance care planning, 125 (81%) received advance care planning, and 108 (84%) expressed wishes or appointed a surrogate, or both. Of the 56 patients who died by 6 months, end-of-life wishes were much more likely to be known and followed in the intervention group (25/29, 86%) compared with the control group (8/27, 30%). In the intervention group, family members of patients who died had significantly less stress (intervention 5, control 15), anxiety (intervention 0, control 3), and depression (intervention 0, control 5) than those of the control patients. Patient and family satisfaction was higher in the intervention group. The authors conclude that advance care planning improves end-of-life care and patient and family satisfaction and reduces stress, anxiety, and depression in surviving relatives.
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;28:3672–3679.
Fatigue is one of the most common symptoms experienced by cancer patients. In this randomized, double-blind, placebo-controlled study, the authors attempted to evaluate the efficacy of long-acting methylphenidate for improving cancer-related fatigue and to assess its side effects and toxicities. Patients with cancer were randomly assigned in a double-blinded manner to receive methylphenidate (target dose, 54 mg/day) or placebo for 4 weeks. The Brief Fatigue Inventory was the primary outcome measure, while 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 among the 148 patients enrolled that there was no evidence that methylphenidate (using an area under the serum concentration–time curve analysis), when compared with placebo improved the primary end point of cancer-related fatigue (p = 0.35). Comparisons of secondary end points, 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, the mean improvement in usual fatigue was 19.7 with methylphenidate versus 2.1 with placebo; p = 0.02). 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 this study was unable to support the pre-study hypothesis that the chosen long-acting methylphenidate product would decrease cancer-related fatigue.