Gerhild Becker

Long-acting octreotide versus placebo for treatment of advanced HCC: a randomized controlled double-blind study.

Although numerous treatment modalities have been explored in patients with advanced HCC, the therapeutic options are still limited. Somatostatin has been shown to have antimitotic activity in endocrine as well as in a variety of nonendocrine tumors. Expression of somatostatin receptors is found in HCCs, but the efficacy of the somatostatin analogue octreotide remains controversial. Therefore, a randomized double‐blind placebo‐controlled multicenter trial was performed to assess the efficacy of long‐acting octreotide for the treatment of advanced HCC. One hundred twenty untreated patients with histologically confirmed HCC were randomized to receive either long‐acting octreotide (Sandostation LAR 30 mg) intramuscularly every 4 weeks or placebo. The study groups were comparable with respect to clinical characteristics. There was no difference in the cumulative survival. The median survival time was 4.7 months in the octreotide group compared with 5.3 months in the control group. Six‐month survival rates were 41% for octreotide patients and 42% for control patients, respectively. The unadjusted relative risk for mortality in the octreotide group compared with patients in the control group was 1.11 (95% CI 0.76‐1.63; P = 0.59). When adjusted for Okuda, CTP, and Cancer of the Liver Italian Program (CLIP) scores, the relative risk for octreotide did not change markedly and was 1.05 (95% CI 0.71‐1.55; P = 0.83). The CLIP score seems to predict survival better than both Okuda and CTP score. Conclusion: The randomized controlled double‐blind HECTOR trial showed no survival benefit for HCC patients treated with long‐acting octreotide compared with placebo. (HEPATOLOGY 2007;45:9–15.)

Novel opioid antagonists for opioid-induced bowel dysfunction and postoperative ileus

Peripherally acting mu-opioid receptor antagonists methylnaltrexone and alvimopan are a new class of drugs designed to reverse opioid-induced side-effects on the gastrointestinal system without compromising pain relief. This article gives an overview of the pharmacology, the efficacy, and adverse effects of these drugs. Both compounds seem to be generally well tolerated and effective for the treatment of opioid-related bowel dysfunction and postoperative ileus. Methylnaltrexone recently received approval by the US Food and Drug Administration (FDA) and the European Medicines Agency for treatment of opioid-related bowel dysfunction in patients with advanced illness. Alvimopan was recently approved by the FDA for treatment of postoperative ileus, but the use of the drug is restricted to inpatients because it has been associated with an increased rate of myocardial infarction. Further research should assess the effectiveness and safety of these drugs in clinical practice.

Emerging treatments in neurogastroenterology: a multidisciplinary working group consensus statement on opioid-induced constipation

Opioids are effective for acute and chronic pain conditions, but their use is associated with often difficult‐to‐manage constipation and other gastrointestinal (GI) effects due to effects on peripheral μ‐opioid receptors in the gut. The mechanism of opioid‐induced constipation (OIC) differs from that of functional constipation (FC), and OIC may not respond as well to most first‐line treatments for FC. The impact of OIC on quality of life (QoL) induces some patients to decrease or stop their opioid therapy to relieve or avoid constipation.

Do religious or spiritual beliefs influence bereavement? A systematic review.

Background: Responses to bereavement may be influenced by characteristics such as age or gender, but also by factors like culture and religion. Aim: A systematic review was undertaken to assess whether spiritual or religious beliefs alter the process of grief and/or bereavement. Methods: Fifteen computerized databases were searched. Thirty-two studies met the inclusion criteria. Evidence was graded according to the standard grading system of the Clinical Outcomes Group and by the SIGNAL score. Results: In total, 5715 persons were examined: 69% women, 87% white, 83% protestant. Ninety-four percent of studies show some positive effects of religious/spiritual beliefs on bereavement, but there was a great heterogeneity regarding included populations and outcome measurements. Conclusion: Available data do not allow for a definite answer on whether religious/spiritual beliefs effectively influence bereavement as most studies suffer from weaknesses in design and methodological flaws. Further research is needed. Recommendations for further research are given. Palliative Medicine 2007; 21: 207—217

Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors: a prospective, randomized, placebo-controlled, double-blind pilot trial.

Patients irradiated for brain tumors often suffer from cerebral edema and are usually treated with dexamethasone, which has various side effects. To investigate the activity of Boswellia serrata (BS) in radiotherapy‐related edema, we conducted a prospective, randomized, placebo‐controlled, double‐blind, pilot trial.

Definitions and outcome measures of clinical trials regarding opioid-induced constipation: a systematic review.

Opioid-induced constipation (OIC) is a frequent symptom in patients treated with opioids and impacts the patients’ quality of life. However, there is no generally accepted definition for OIC. The aims of this study were to identify definitions for OIC in clinical trials and Cochrane Reviews and to compile assessment tools and outcome measures that were used in clinical trials. In a systematic review, 5 databases (MEDLINE, PubMed, The Cochrane Library, Web of Science, and EMBASE) were searched to identify clinical trials assessing OIC in adult patients or healthy volunteers. Studies published between 1993 and August 2013 were included. A total of 1488 studies were retrieved and 47 publications were included in the analysis. A minority of the publications (n=16, 34%) provided a clear definition for OIC. The definitions were highly variable and the present or recent history of opioid therapy was frequently (n=6, 38%) not included in these definitions. Of 46 clinical trials, 17 (37%) relied exclusively on objective measures such as bowel movement frequency, whereas another 17 studies additionally included patient-reported outcome measures such as, “feeling of incomplete bowel evacuation.” Few trials (n=7, 15%) assessed the patient-reported global burden of OIC. Standard definitions and outcome measures are necessary (i) for consistency in OIC diagnosis in clinical practice and clinical trials; and (ii) to assure comparability of trial findings (eg, in meta-analyses). An OIC definition and outcome measures are proposed.

Stereotactic fractionated radiotherapy for Klatskin tumours

BACKGROUND AND PURPOSE In spite of various efforts perihilar cholangiocellular carcinoma (Klatskin tumour) has still a bad prognosis. The treatment of patients with inoperable Klatskin tumours by stereotactic fractionated radiotherapy (SFRT) was analysed retrospectively. PATIENTS, METHODS AND MATERIALS: In our department 13 patients were treated for Klatskin tumours by SFRT (32-56 Gy, 3 x 4 Gy/week) from 1998 to 2008. The treatment technique was developed from stereotactic body frame radiotherapy to image guided (IGRT) stereotactic radiotherapy with control of patient positioning by cone beam computer tomography (CBCT). 6/13 patients received additional chemotherapy before or after SFRT. RESULTS A median survival of 33.5 (6.6-60.4) months after diagnosis was reached by SFRT. The median time of freedom from tumour progression was 32.5 (6.1-60.4, last patient died without tumour progression) months. The therapy was tolerated very well. Nausea was the most common side effect. 5/13 patients suffered from recurrent cholangitis caused and enhanced by the primary tumour and drainages or stents in the bile ducts. CONCLUSIONS In the context of reaching local control being still the main problem of Klatskin tumour patients, SFRT seems to be a very promising method for the treatment of these tumours.

Religious belief as a coping strategy: an explorative trial in patients irradiated for head-and-neck cancer.

Purpose:To explore the role of religious belief in coping with disease symptoms and treatment-related side effects in patients with head-and-neck cancer under radiotherapy.Patients and Methods:Prospectively collected data were used with a cohort of head-and-neck cancer patients treated by radiotherapy and epoetin beta or placebo within a double-blind multicenter trial. All patients were divided into believers and nonbelievers. Answers to a quality of life questionnaire at four points in time during radiotherapy were analyzed according to both groups. Clinical parameters and therapy side effects were controlled regularly.Results:62.1% of the patients (66/105) sent back a baseline questionnaire discriminating between believers and nonbelievers. For 34.2% (40/105) data of all four measures could be obtained. On average, believers felt better in all categories of side effects at all points of time before, during and directly after therapy.Conclusion:Religious faith seems to play an important role in coping strategies of radiotherapy patients. More research in this area would be worthwhile.Ziel:Ziel der vorliegenden Untersuchung war es, die Rolle des religiösen Glaubens bei der Verarbeitung („Coping“) von Krankheitssymptomen und behandlungsbedingten Nebenwirkungen an Strahlentherapie-Patienten mit Kopf-Hals-Tumoren zu untersuchen.Patienten und Methodik:Die Studie wurde mit prospektiv erhobenen Daten an einer Kohorte von Patienten mit Kopf-Hals-Tumoren, die in einer doppelblinden Multicenterstudie mit einer Strahlentherapie und Epoetin beta oder Plazebo behandelt wurden, durchgeführt. Die Patienten wurden in zwei Gruppen, „Gläubige“ und „Nichtgläubige“, eingeteilt. Während der Therapie wurden, bezogen auf die beiden Gruppen, die Antworten auf einen Lebensqualitätsfragebogen zu vier Zeitpunkten ausgewertet. Klinische Parameter und Nebenwirkungen der Therapie wurden laufend kontrolliert.Ergebnisse:62,1% der Patienten (66/105) schickten den Basisfragebogen zurück, durch den zwischen Gläubigen und Nichtgläubigen unterschieden wurde. Für 32,2% der Patienten (40/105) konnten die Daten zu allen vier Messzeitpunkten ermittelt werden. Bezüglich aller erfassten Nebenwirkungen fühlten sich die Gläubigen über den gesamten Messzeitraum (vor, während und nach der Strahlentherapie) besser als die Nichtgläubigen.Schlussfolgerung:Der religiöse Glaube scheint für Copingstrategien bei Strahlentherapie-Patienten eine wichtige Rolle zu spielen, so dass dieses Gebiet weiter untersucht werden sollte.

Xerostomia after radiotherapy in the head & neck area: long-term observations.

To investigate the development of xerostomia more than 5 years after radiotherapy for head and neck cancer, a prospective longitudinal study was done. A xerostomia questionnaire was answered by 42 patients 41 and 90 months after radiotherapy: xerostomia at rest did not change significantly over time whereas the difficulties with speaking improved and the difficulties with eating worsened. Subjective xerostomia does not reach a steady state even more than 5 years after radiotherapy.

Methylnaltrexone for the treatment of opioid-induced constipation

Opioids are the drugs of choice for treating moderate-to-severe pain, especially for patients in the end stage of cancer or other advanced illnesses, and also in critical care or for the treatment of chronic pain. Side effects such as nausea, pruritus, dizziness and constipation have to be controlled in order to use these drugs to their full potential. Opioid-induced bowel syndrome and constipation caused by activation of μ-receptors in the gut can have such distressing effects that some patients prefer to forego adequate pain control. Methylnaltrexone is a μ-opioid receptor antagonist that, unlike naltrexone or naloxone, does not pass the blood–brain barrier, and therefore does not impair the centrally mediated analgesic effect of opioids. It is licensed for the treatment of opioid-induced constipation in palliative care in more than 50 countries. This article presents practically relevant pharmacological data, basic research results and evidence from clinical research about methylnaltrexone, and outlines potential future therapeutic options for this promising drug.