<b>PURPOSE: </b>Corticosteroids are frequently used in cancer pain management despite limited evidence. This study compares the analgesic efficacy of corticosteroid therapy with placebo.<b>Patients and METHODS: </b>Adult patients with cancer receiving opioids with average pain intensity ≥ 4 (numeric rating scale [NRS], 0 to 10) in the last 24 hours were eligible. Patients were randomly assigned to methylprednisolone (MP) 16 mg twice daily or placebo (PL) for 7 days. Primary outcome was average pain intensity measured at day 7 (NRS, 0 to 10); secondary outcomes were analgesic consumption (oral morphine equivalents), fatigue and appetite loss (European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire C30, 0 to 100), and patient satisfaction (NRS, 0 to 10).<b>RESULTS: </b>A total of 592 patients were screened; 50 were randomly assigned, and 47 were analyzed. Baseline opioid level was 269.9 mg in the MP arm and 160.4 mg in the PL arm. At day-7 evaluation, there was no difference between the groups in pain intensity (MP, 3.60 v PL, 3.68; P = .88) or relative analgesic consumption (MP, 1.19 v PL, 1.20; P = .95). Clinically and statistically significant improvements were found in fatigue (-17 v 3 points; P .003), appetite loss (-24 v 2 points; P = .003), and patient satisfaction (5.4 v 2.0 points; P = .001) in favor of the MP compared with the PL group, respectively. There were no differences in adverse effects between the groups.<b>CONCLUSION: </b>MP 32 mg daily did not provide additional analgesia in patients with cancer receiving opioids, but it improved fatigue, appetite loss, and patient satisfaction. Clinical benefit beyond a short-term effect must be examined in a future study.
CONTEXT: The vertebral column is the most common site of bone metastases irrespective of the primary tumor. Vertebral metastases are a major cause of motor deficit of the lower extremities. The use of radiotherapy is the treatment of choice in these patients. A temporary worsening of pain shortly during the course of palliative radiotherapy is clinically a common problem. Steroid infusion has well-documented neuroprotective effects. OBJECTIVES: Our study objective is to evaluate the effect of pre-emptive infusion of methylprednisolone on pain flare and motor function in patients with vertebral metastases. METHODS: One hundred twenty patients with vertebral metastases received short-course external beam radiotherapy as high-voltage irradiation with a 6 MeV, via linear accelerator. In addition to the short-course radiotherapy, 60 patients received pre-emptive methylprednisolone infusion (5 mg/kg) the day just before initiation of radiotherapy (Group 1 [G1]). The other 60 patients received short-course radiotherapy without pretreatment methylprednisolone infusion, and only normal saline was infused (Group 2 [G2]). The Brief Pain Inventory, incidence of pain flare during radiotherapy, and motor functions were evaluated using the Tomita scale at the time of initial assessment, at the end of external beam radiotherapy, and after two weeks. RESULTS: Four patients (6.6%) in G1 experienced pain flare compared with 12 patients (20%) in G2 during the two-week short-course radiotherapy. The mean values of pain scores were significantly reduced in both groups at the end of radiotherapy; the mean value of worst, average, and current pain scores in G1 remained statistically significant in comparison to pretreatment and G2 mean values two weeks later. Significant increase was noticed in patients with normal motor and ambulatory status in G1 at two and four weeks of initial assessment. CONCLUSION: Pre-emptive methylprednisolone infusion is an effective prophylactic agent in the prevention of radiation-induced pain flare and improves functional motor status after short-term radiotherapy in patients with vertebral metastases.
OBJECTIVE: To assess the efficacy and safety of gabapentin and amitriptyline along with opioids in patients suffering from neuropathic pain in malignancy.
MATERIALS AND METHODS: Eighty-eight adult patients between 18 and 70 years of age with neuropathic pain in stage III malignant disease, matched for baseline charactistics, were randomly assigned to two groups. Group A received oral tramadol and gabapentin and group B received oral tramadol and amitriptyline. The treatment duration of each patient was 6 months. Visual analog scale (VAS) was the primary efficacy parameter. Verbal rating scale (VRS) score, percentage of pain relief (PPR), and global pain score (GPS) were the secondary efficacy parameters. Oral morphine tablets or fentanyl transdermal patch were used as rescue medication. Data analysis was carried out in Graph Pad instat.
RESULTS: There was decline in VAS pain score from baseline in both the groups in the early phase of the study though there was no statistically detectable difference between them at any study point. Similar changes were seen in the secondary efficacy parameters too. Thus both the drugs were effective in providing relief to cancer patients with neuropathic pain though there was no statistically detectable difference in efficacy between them. Six patients in group A and eight patients in group B required rescue medication. A total of 12 subjects in the gabapentin group and 15 subjects in the amitriptyline group experienced adverse events which were of mild to moderate grades.
CONCLUSIONS: Amitriptyline may be a suitable alternative for management of neuropathic pain in cancer patients although gabapentin is widely used for this purpose. The lower cost of amitriptyline may favor patient compliance with lesser number of drop-outs.
OBJECTIVES: : The aim of this study was to evaluate the opioid response in patients receiving morphine and pregabalin, independently from the presumed pain mechanisms, in comparison with patients receiving morphine treatment only. METHODS: : A multicenter prospective randomized controlled study was carried out in a sample of 70 advanced cancer patients with pain requiring strong opioids. Thirty-five patients (group MO) were randomized to receive sustained-release morphine using initial doses of 60 mg/day. Thirty-five patients (group MO-PR) were randomized to start the same morphine doses and pregabalin in increasing doses, starting with 25 mg/day up to 150 mg/day in one week. The following data were also recorded before starting the treatments (T0) and then at week intervals for four weeks (W1-4): age, gender, primary cancer and known metastases, pain causes and mechanisms, symptoms associated with opioid therapy, pain intensity, Brief Pain Inventory (BPI), morphine doses and escalation indexes (OEIs), and quality of life. RESULTS: : Forty-eight patients completed the study, twenty-eight and sixteen patients in group MO and MO-PR, respectively. Twenty patients were females, the mean age was 65.5 (±10.3), and the mean Karnofsky status was 66.0 (±18.9). No differences between groups were found in age (P=0.839), Karnofsky status (P=0.741), opioid doses as well as escalation indexes (OEI mg, P=0.260, and OEI%, P=0.270). No differences between the two groups were found in quality of life and all BPI items. CONCLUSION: : The use of low doses of pregabalin added to morphine therapy in advanced cancer patients does not seem to provide advantageous analgesic effects, despite limitations of the present study due to the number of drop-outs.
BACKGROUND: In this study, the authors evaluated the effect of denosumab versus zoledronic acid (ZA) on pain in patients with advanced breast cancer and bone metastases. METHODS: The prevention of pain, reduction in pain interference with daily life activities, and the proportion of patients requiring strong opioid analgesics were assessed in a randomized, double-blind, double-dummy phase 3 study comparing denosumab with ZA for preventing skeletal-related events in 2046 patients who had breast cancer and bone metastases. Patients completed the Brief Pain Inventory-Short Form at baseline and monthly thereafter. RESULTS: Fewer patients who received denosumab reported a clinically meaningful worsening of pain severity (≥2-point increase) from baseline compared with patients who received ZA, and a trend was observed toward delayed time to pain worsening with denosumab versus ZA (denosumab, 8.5 months; ZA, 7.4 months; <i>P</i> = .08). In patients who had no/mild pain at baseline, a 4-month delay in progression to moderate/severe pain was observed with denosumab compared with ZA (9.7 months vs 5.8 months; <i>P</i> = .002). Denosumab delayed the time to increased pain interference by approximately 1 month compared with ZA (denosumab, 16.0 months; ZA, 14.9 months; <i>P</i> = .09). The time to pain improvement (<i>P</i> = .72) and the time to decreased pain interference (<i>P</i> = .92) were similar between the groups. Fewer denosumab-treated patients reported increased analgesic use from no/low use at baseline to strong opioid use. CONCLUSIONS: Denosumab demonstrated improved pain prevention and comparable pain palliation compared with ZA. In addition, fewer denosumab-treated patients shifted to strong opioid analgesic use. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
CONTEXT: Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group.
OBJECTIVES: This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer.
METHODS: In total, 43 patients with cancer-related pain experiencing inadequate analgesia despite chronic opioid dosing, who had participated in a previous three-arm (THC/CBD spray, THC spray, or placebo), two-week parent randomized controlled trial, entered this open-label, multicenter, follow-up study. Patients self-titrated THC/CBD spray (n=39) or THC spray (n=4) to symptom relief or maximum dose and were regularly reviewed for safety, tolerability, and evidence of clinical benefit.
RESULTS: The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for "pain severity" and "worst pain" domains showed a decrease (i.e., improvement) at each visit in the THC/CBD spray patients. Similarly, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 scores showed a decrease (i.e., improvement) from baseline in the domains of insomnia, pain, and fatigue. No new safety concerns associated with the extended use of THC/CBD spray arose from this study.
CONCLUSION: This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit.
PURPOSE: Neuropathic pain is commonly associated with cancer. Current treatments include combination opioid and adjuvant therapies, but no guidelines are available for dose escalation strategies. This phase II study compared the efficacy and tolerability of two dose escalation strategies for oxycodone and pregabalin combination therapy.
METHODS: Patients (N = 75) with oncological neuropathic pain, previously untreated with pregabalin, were recruited in 5 Italian institutions between 2007 and 2010. Patients were randomised to two different dose escalation strategies (arm A; N = 38) oxycodone at a fixed dose with increasing pregabalin doses; (arm B; N = 37) pregabalin at a fixed dose with increasing oxycodone doses. Patients were evaluated from daily diaries and follow-ups at 3, 7, 10, and 14 days after beginning treatment with a numerical rating scale (NRS), neuropathic pain scale (SDN), and well-being scale (ESAS). The primary endpoint was a ≥1/3 reduction in pain (NRS); secondary endpoints included the time to analgesia and adverse effects. The study had a 90% probability of detecting the best strategy for a true difference of at least 15%.
RESULTS: More patients in arm A (76%) than arm B (64%) achieved ≥1/3 overall pain reduction even after controlling for baseline factors (gender, baseline pain). Group A reported fewer side effects than group B; constipation 52.8% vs. 66.7%; nausea: 27.8% vs. 44.4%; drowsiness: 44.4% vs. 55.6%; confusion: 16.7% vs. 27.8%; itching: 8.3% vs. 19.4%.
CONCLUSIONS: Both strategies effectively controlled neuropathic pain, but according to the adopted selection design arm A is preferable to arm B for pain control.
TRIAL REGISTRATION: ClinicalTrials.gov NCT00637975.
