Dominique Lossignol

Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study of the Efficacy, Safety, and Tolerability of THC:CBD Extract and THC Extract in Patients with Intractable Cancer-Related Pain

This study compared the efficacy of a tetrahydrocannabinol:cannabidiol (THC:CBD) extract, a nonopioid analgesic endocannabinoid system modulator, and a THC extract, with placebo, in relieving pain in patients with advanced cancer. In total, 177 patients with cancer pain, who experienced inadequate analgesia despite chronic opioid dosing, entered a two-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial. Patients were randomized to THC:CBD extract (n = 60), THC extract (n = 58), or placebo (n = 59). The primary analysis of change from baseline in mean pain Numerical Rating Scale (NRS) score was statistically significantly in favor of THC:CBD compared with placebo (improvement of -1.37 vs. -0.69), whereas the THC group showed a nonsignificant change (-1.01 vs. -0.69). Twice as many patients taking THC:CBD showed a reduction of more than 30% from baseline pain NRS score when compared with placebo (23 [43%] vs. 12 [21%]). The associated odds ratio was statistically significant, whereas the number of THC group responders was similar to placebo (12 [23%] vs. 12 [21%]) and did not reach statistical significance. There was no change from baseline in median dose of opioid background medication or mean number of doses of breakthrough medication across treatment groups. No significant group differences were found in the NRS sleep quality or nausea scores or the pain control assessment. However, the results from the European Organisation for Research and Treatment of Cancer Quality of Life Cancer Questionnaire showed a worsening in nausea and vomiting with THC:CBD compared with placebo (P = 0.02), whereas THC had no difference (P = 1.0). Most drug-related adverse events were mild/moderate in severity. This study shows that THC:CBD extract is efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids.

Opioid switch to oral methadone in cancer pain.

The occurrence of undesirable side effects due to opioids (delirium, confusion, myoclonus, nausea, emesis) is one of the major complications in the management of pain, especially in chronic cancer pain states. Methadone, as an alternative to morphine, has been proposed in the control of opioid-induced toxicity. Methadone is a synthetic opioid, with μ and δ receptor activity, associated with the capacity to inhibit N-methyl-D-aspartate receptors. Questions have arisen concerning its equianalgesic ratio since its rediscovery over the past few years and are certainly related to its receptor interactions. Aspects of its pharmacology, indications, and switching modalities are discussed here. Opioid rotation is a new tool in the management of cancer pain, deserving more attention.

The concept of rehabilitation of cancer patients.

The scope of supportive care and cancer rehabilitation is very wide and heterogeneous. In this review we focus on nutritional aspects, sexual and gonadal function, psychological rehabilitation, treatment of cancer pain, and rehabilitation of patients with bone metastases. The anorexia-cachexia syndrome is a particularly frequent manifestation of cancer that profoundly affects body image and significantly impairs quality of life of cancer patients. However, enteral feeding through nasogastric tubes, gastrostomies, or jejunostomies is an efficient method for providing long-term enteral nutrition at home and for contributing to complete rehabilitation after cancer therapy. Recent effort has focused on nutritional pharmacology and on the optimalization of the use of appetite-stimulating drugs, such as progestational agents. The psychological components of cancer, anticancer therapy, and quality of life have now been widely recognized and studied. Effective pharmacological and psychotherapeutic interventions help patients and their family to better adjust to the chronic stress of cancer, but more specific determinants of psychological morbidity should be developed. In particular, the safe and efficient use of the most recent classes of antidepressants and anxiolytics should be urgently studied. More than 90% of cancer patients present one or more pain syndromes during their illness. The adequate use of drugs is the cornerstone of treatment. The development on new molecules and new routes of administration opens interesting perspectives for cancer pain control. Bone metastases are the source of considerable morbidity. Intravenous bisphosphonates have been successfully used for the treatment of the symptoms of metastatic bone disease, especially bone pain. Moreover, monthly pamidronate infusions in addition to chemotherapy reduce the mean skeletal morbidity rate by more than one third and contribute to the rehabilitation of cancer patients with bone metastases from breast cancer or with multiple myeloma.

Brain metastases in HER2-positive breast cancer: The evolving role of lapatinib

Due to improvements in diagnosis and systemic therapy, brain metastases are an increasingly common cause of morbidity and mortality for patients with advanced breast cancer. The incidence of symptomatic brain metastases among women with metastatic breast cancer ranges from 10% to 16%. The HER2 receptor, which is overexpressed in approximately 25% of all breast cancers, is an important risk factor for the development of central nervous system metastases. Surgery and radiation therapy are the primary approaches to the treatment of brain metastases but new chemotherapy and biological agents promise to play an important role in the future management of central nervous system disease. This article reviews the epidemiology, current treatment options and recent advances in the field, with a focus on HER2-positive disease and the emerging role of lapatinib for the treatment and prevention of brain metastases.

Breakthrough pain: progress in management.

Purpose of review To present recent developments in the treatment of breakthrough pain (BTP) in cancer, we reviewed the literature with a special focus on last publications using Medline. Recent findings BTP is distinguished from other pain syndromes because of its unique physiopathology, clinical and socio-economic importance and treatment considerations. Despite medical awareness, BTP remains underdiagnosed and therefore undertreated. Clinical information is essentially based on case series and expert opinion. Fentanyl, oral or nasal, remains the molecule of choice to treat BTP, but very important development is ongoing to improve tolerance, efficacy and pharmacokinetics. Summary Data from epidemiological and clinical studies show that breakthrough pain remains a challenge especially among cancer patients. An accurate diagnosis followed by a specific treatment is the key for an effective pain relief.

End-of-life sedation: is there an alternative?

Purpose of review To evaluate the place and the usefulness of sedation in medical practice at the end of life. Recent findings Continuous sedation is an acknowledged medical practice for the management of refractory symptoms at the end of life. Guidelines and recommendations have been proposed in palliative care. Although considered as a good medical practice at the end of life, sedation is neither the only option nor the best. Summary This article presents the state-of-the-art (definitions, indications, and technical aspects) about continuous sedation, followed by an ethical reflection essentially based on the ‘Principle of Double Effect’, the impact on life expectancy, and the concept of ‘natural death’.

Intrathecal Trastuzumab Treatment of the Neoplastic Meningitis due to Breast Cancer: A Case Report and Review of the Literature

We report the case of a 65-year-old woman, diagnosed with a breast cancer human epidermal growth factor receptor (HER2) previously negative, who developed leptomeningeal carcinomatosis and was treated with intrathecal (IT) trastuzumab (TST). After five doses of IT trastuzumab, at escalading doses, once weekly, the patients neurological status stabilised, and that result was maintained for two months. There is evidence in the literature that breast cancer receptor status may change over time, and when it occurs, it may modify the therapeutical approach. We reviewed the pertinent literature and concluded that IT trastuzumab might be a promising treatment for patients with HER2-positive breast cancer leptomeningeal carcinomatosis.

Narrative ethics in the field of oncology.

Purpose of review To evaluate the application of narrative within medical practice. Illness like cancer constitutes a biographical disruption that occurs several times during the disease, from diagnosis to complications and treatments. This review analyzes the interest of narrative ethics in medicine with a focus on cancer. Recent findings The field of narrative ethics in medicine has emerged from a confluence of humanities, contemporary narratology, literature and social sciences. Although there is a growing literature on this topic, little has been written on an oncology setting. This article is more a personal consideration on the subject than a classical review of the literature. Summary The advent of bioethics has given considerable insight into the practice of medicine, and it would be inconceivable to return to a paternalistic practice that ignores the will of the patient. Like procedural ethics of discussion, and in complement with principlism, narrative ethics promotes constructive communication between patients and caregivers.

Psychological interventions to reduce pain in patients with cancer

Purpose of review To review relevant studies about psychological interventions among patients with cancer pain. Recent findings We used MEDLINE as a source of studies on psychological interventions between January 2012 and December 2012. Most studies were randomized, but there was no homogeneity in terms of psychological intervention types or pain evaluation. Summary Not all studies with psychological interventions measured pain as a primary outcome; pain was measured inconsistently across studies, pain raters were rarely blinded, few studies carefully described the other treatments (pharmacological or not), and patients were observed for only a limited period of time. Despite these limitations, the positive findings of this review advance support for the importance of psychological interventions on reducing pain among patients with cancer, and for the implementation of quality-controlled psychosocial interventions as part of a multimodal approach to the management of pain.

Pitfalls in the use of opiates in treatment of cancer pain

The use of morphine in the treatment of cancer pain is widely accepted among people taking care of cancer patients and concerned with pain relief. Several problems regarding common side-effects, lifethreatening complications in cancer and opioid-non-responsive pain syndromes will be discussed. The development of grading systems may open new directions for adequate pain control.