RESUMEN
BACKGROUND: Cannabinoids are often prescribed for neuropathic pain, but the evidence-based recommendation is 'weak against'. OBJECTIVES: The aim was to examine the effect of two cannabinoids and their combination in peripheral neuropathic pain. METHODS: This was a randomized, double-blind, trial with treatment arms for cannabidiol (CBD), tetra-hydro-cannabinol (THC), CBD and THC combination (CBD/THC), and placebo in a 1:1:1:1 ratio and flexible drug doses (CBD 5-50 mg, THC 2.5-25 mg, and CBD/THC 5 mg/2.5 mg-50 mg/25 mg). Treatment periods of 8-week duration were proceeded by 1 week for baseline observations. Patients with painful polyneuropathy, post-herpetic neuralgia and peripheral nerve injury (traumatic or surgical) failing at least one previous evidence-based pharmacological treatment were eligible for inclusion. The primary outcome was the change in weekly average of daily pain measured with a numeric rating scale (NRS). Trail Making Test (TMT) was used as one of the tests of mental functioning. RESULTS: In all, 145 patients were included in the study of which 118 were randomized and 115 included in the intention-to-treat analysis. None of the treatments reduced pain compared to placebo (p = 0.04-0.60). Effect sizes as estimated in week 8 (positive values worse and negative better than placebo) were CBD mean 1.14 NRS points (95% CI 0.11-2.19), THC 0.38 (CI -0.65 to 1.4) and CBD/THC -0.12 (-1.13 to 0.89). CONCLUSIONS: CBD, THC and their combination did not relieve peripheral neuropathic pain in patients failing at least one previous evidence-based treatment for neuropathic pain.
Asunto(s)
Cannabidiol , Neuralgia , Humanos , Cannabidiol/uso terapéutico , Cannabinol/uso terapéutico , Dronabinol/uso terapéutico , Neuralgia/tratamiento farmacológicoRESUMEN
BACKGROUND: An aging population will increase the number of older patients with metastatic colorectal cancer (mCRC). However, there is limited knowledge about treatment in older patients as they are under-represented in clinical trials. The oral fluoropyrimidine S-1 is associated with a lower rate of adverse events than capecitabine and may therefore be a suitable drug for elderly. However, data on the use of S-1 in Caucasian mCRC patients are lacking/scarce. MATERIAL AND METHODS: In the present study we evaluated safety and the efficacy of S-1 alone or in combination with oxaliplatin (SOx) or irinotecan (IRIS) in older mCRC patients. Patients who received at least one cycle of S-1 (first-line therapy), SOx (mainly first-line therapy) or IRIS (second-line therapy) were included. RESULTS: From June 2012 to December 2014, 71 older patients received ≥1 cycle of either S-1 (n = 9), SOx (n = 44) or IRIS (n = 18) for mCRC. Median age was 76 years and most patients had a WHO performance status of 0 (32%) or 1 (56%). All patients were evaluable for response and safety. In the SOx group, 18 (41%) and 20 patients (45%) had partial response (PR) and stable disease (SD), respectively (disease control rate 86%). Median progression-free survival (PFS) was 8.5 months and median overall survival (OS) was 18.5 months. In the S-1 group (median age 82 years), PR was 22%, median PFS 6.4 months and median OS 15.8 months. In the IRIS group, PR was 28%, median PFS 7.8 months and the median OS 16.5 months. In general, therapy was well tolerated; main non-hematological toxicities were fatigue and diarrhea. CONCLUSION: S-1 monotherapy, SOx and IRIS were well tolerated for older patients with mCRC and could become alternative regimens in older mCRC patients. These regimens are now further evaluated in the randomized ongoing NORDIC9 trial.