Can treatment success with 5% lidocaine medicated plaster be predicted in cancer pain with neuropathic components or trigeminal neuropathic pain?

An expert group of 40 pain specialists from 16 countries performed a first assessment of the value of predictors for treatment success with 5% lidocaine-medicated plaster in the management of cancer pain with neuropathic components and trigeminal neuropathic pain. Results were based on the retrospective analysis of 68 case reports (sent in by participants in the 4 weeks prior to the conference) and the practical experience of the experts. Lidocaine plaster treatment was mostly successful for surgery or chemotherapy-related cancer pain with neuropathic components. A dose reduction of systemic pain treatment was observed in at least 50% of all cancer pain patients using the plaster as adjunct treatment; the presence of allodynia, hyperalgesia or pain quality provided a potential but not definitively clear indication of treatment success. In trigeminal neuropathic pain, continuous pain, severe allodynia, hyperalgesia, or postherpetic neuralgia or trauma as the cause of orofacial neuropathic pain were perceived as potential predictors of treatment success with lidocaine plaster. In conclusion, these findings provide a first assessment of the likelihood of treatment benefits with 5% lidocaine-medicated plaster in the management of cancer pain with neuropathic components and trigeminal neuropathic pain and support conducting large, well-designed multicenter studies.

[Leptomeningeal meningitis related to breast cancer overexpressing HER2: is there a place for a more specific treatment?]. / Méningites carcinomateuses des cancers du sein surexprimant HER2 : pour un traitement spécifique ?

Leptomeningeal metastases are very commonly associated with breast cancer. The prognosis is very poor in the short term with an overall median survival less than 6 months. Based on pragmatic and historical considerations intrathecal chemotherapy (IT) are considered to be the adequate treatment. However overall results are disappointing. Despite specific and symptomatic treatment, improvement in survival and quality of life remains very modest, highlighting the importance for ongoing research for developing new molecules or on improving the use a better use of those available today. The incidence of leptomeningeal metastases is particularly marked in cases of overexpression of HER2. The main hypothesis is there may be a better control of extra-cerebral localisations with trastuzumab therefore intra-cerebral recurrences may be encountered preferentially as they are not reached by this high molecular weight monoclonal antibody (148  kD). Analyses performed in the cerebrospinal fluid following intravenous trastuzumab showed extremely low levels of the antibody and support the hypothesis that leptomeningeal metastasis of HER2-overexpressing breast carcinoma remain potentially sensitive to HER2-type receptor inhibition by a target agent under the condition of by-passing the meningeal blood brain barrier. Intra-ventricular or IT administered with trastuzumab would reach high loco-regional therapeutic concentrations in the cerebro-meningeal without risk for normal non-expressing HER2 leptomeningeal tissue. This strategy has been successfully tested on several animal models. A limited number of administrations in humans have been described in the literature, with weekly doses up to 100  mg. No specific toxicity has been described and some data suggest a potential benefit in survival despite the real difficulties for adequate interpretations. Furthermore, a multicentric phase I-II clinical trial, of which the Curie institute is the sponsor and investigating the intra-thecal administration and the efficacy of the trastuzumab will begin very soon. More studies are needed to measure the exact impact of small molecule inhibitors of tyrosine kinase on the leptomeningeal localizations.

Outcome predictors for treatment success with 5% lidocaine medicated plaster in low back pain with neuropathic components and neuropathic pain after surgical and nonsurgical trauma.

Five percent lidocaine medicated plaster has been proven efficacious for the symptomatic relief of neuropathic pain in diverse pain conditions which might be attributed to a common localized symptomatology in these indications, possibly with common predictors of treatment success. To discuss potential symptoms and other factors predicting response to treatment with lidocaine plaster for the indications of low back pain with neuropathic components and neuropathic pain after surgical and nonsurgical trauma, 44 pain specialists from 17 countries attended a two-day conference meeting in December 2009. Discussions were based on the retrospective analysis of case reports (sent in by participants in the four weeks prior to the meeting) and the practical experience of the participants. The results indicate some predictors for success with 5% lidocaine medicated plaster for the two indications. Localized pain, hyperalgesia and/or allodynia, and other positive sensory symptoms, such as dysesthesia, were considered positive predictors, whereas widespread pain and negative sensory symptoms were regarded as negative predictors. Paresthesia, diagnosis, and site of pain were considered to be of no predictive value. Common symptomatology with other neurologic pathologies suggests that treatment of localized neuropathic pain symptoms with the plaster can be considered across different neuropathic pain indications.

Cancer-related symptom assessment in France: validation of the French M. D. Anderson Symptom Inventory.

This multicenter study was intended to validate the French version of the M. D. Anderson Symptom Inventory (MDASI-Fr) in French cancer patients (n=162) with solid tumors or hematological malignancies. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) was used as a part of the validation. Factor analysis showed three underlying constructs for symptom items: general symptoms (pain, fatigue, disturbed sleep, shortness of breath, drowsiness, dry mouth, and numbness or tingling items); emotional and cognitive components (distress, sadness, and remembering items); and a gastrointestinal component (nausea, vomiting, and lack of appetite items), with Cronbach's alphas of 0.79, 0.73, and 0.71, respectively. Convergent validity was established by comparing MDASI-Fr items with the EORTC QLQ-C30 scale and the Brief Pain Inventory (BPI). Overall, the 19-item MDASI-Fr score correlated well with the QLQ-C30 global health status, and the pain item of the MDASI-Fr was highly correlated with the short form of the BPI. The most prevalent symptoms were fatigue, distress, dry mouth, and pain. Twenty-five percent of patients reported moderate or severe pain (numeric rating scale >4 on 0-10 severity ratings). Physician ratings of global change on a second visit were significantly associated with changes in patient ratings on the MDASI-Fr, supporting the sensitivity of the measure. Symptoms interfered most with work and general activity. The MDASI-Fr is a valid and reliable tool for measuring symptom severity and interference in French cancer patients.

[The therapeutic use of D9-tetrahydrocannabinol (dronabinol) in refractory neuropathic pain]. / Utilisation thérapeutique du D9-tétrahydrocannabinol (dronabinol) dans les douleurs neuropathiques réfractaires.

INTRODUCTION: Despite the recent discovery of the potential mechanisms underlying the analgesic effects of cannabis, few clinical studies have so far assessed its analgesic effects, notably in the treatment of chronic non-malignant pain. All the studies used administration of cannabis alone. The aim of this open, pilot, study was to assess the efficacy and side effect profile of oral dronabinol (tetrahydrocannabinol - THC) in the treatment of refractory neuropathic pain. METHODS: Seven patients (3 women/4 men), aged 60 +/- 14 years, suffering from chronic refractory neuropathic pain, received oral THC titrated to the maximum dose of 25 mg/day (mean dose: 15 +/- 6 mg), during an average of 55,4 days (range: 13-128). Various components of pain (continuous, paroxysmal and brush-induced allodynia) were assessed using VAS scores. Health-related Quality of Life (HRQL) was evaluated using the Brief Pain Inventory, and the Hospital Anxiety and Depression scale was used to measure depression and anxiety. RESULTS: THC did not induce significant effect on the various pain, HRQL and anxiety and depression scores. Numerous side effects (notably sedation and asthenia) were observed in 5 patients out of 7, requiring premature discontinuation of the drug in 3 patients. CONCLUSION: The present study did not reveal any significant efficacy of THC in a small cohort of patients with chronic refractory neuropathic pain, but underlined the unfavorable side effect profile of the drug. These results may partly relate to the fact that oral dronabinol exhibits a poor therapeutic ratio (efficacy at the price of side effects). The development of new and better tolerated cannabinoids is warranted.