Objective: The present study aims to explore the effectiveness and safety of low‐dose strong opioids compared with non‐steroidal anti‐inflammatory drugs (NSAIDs) in the treatment of mild cancer pain. Methods: From September 2016 to September 2018, 66 patients with a malignant tumor and mild cancer pain admitted to the Department of Oncology of Dalian Fifth People’s Hospital were divided into the group A (treated with ibuprofen sustained‐release tablets for pain relief) and the group B (treated with oxycodone hydrochloride sustained‐release tablets for pain relief). After 7 days of treatment, the pain relief (Numeric Rating Scale [NRS]), physical strength, quality of life scores (Zubrod/ECOG/WHO [ZPS]), the Edmonton Symptom Assessment System [ESAS], and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Core15‐Palliative [EORTC QLQ‐C15‐PAL] scores), and the occurrence of adverse reactions between the two groups were compared. The occurrence of adverse reactions in the mid‐term (after one month and three months of treatment) between the two groups were also compared. Results: Both groups had over 90% analgesic efficiency, but complete pain relief was more likely to be obtained in the group B (41.18%). The total analgesic efficiency in the group B was higher (100%) than in the group A (98.9%), and the difference was statistically significant (P < 0.05). The differences in the physical strength and quality of life scores in the two groups before and after treatment were statistically significant (P < 0.05). The differences in the ZPS scores between the two groups were statistically significant (P < 0.05). The differences in ESAS and EORTC QLQ‐C15‐PAL scores between groups were not statistically significant (P > 0.05). Conclusion: The application of low‐dose oxycodone hydrochloride sustained‐release tablets as the initial medication for patients with mild cancer pain was safe and effective, and the adverse reactions were easy to manage.
CONTEXT: Opioids are frequently used for the treatment of moderate-to-severe pain and their use may produce a number of unwanted adverse events (AEs).
OBJECTIVES: The objective of this study was to understand the burden of opioid-induced AEs in cancer patients with pain after the introduction of strong opioids (WHO Step III).
METHODS: This is a cohort study derived from a randomized controlled trial involving 498 cancer patients with pain who received strong opioids. During 28-day follow-up, we analyzed frequency, intensity, and changes over time of the main opioid-induced AEs; the influence of previous pain therapy on AEs; and the relationships between the presence of AEs and analgesic response.
RESULTS: After starting strong opioids, dry mouth, nausea, and vomiting immediately increased and persisted over time, constipation continued to increase, while drowsiness and confusion tended to decrease. Patients previously treated with weak opioids had more frequent and severe AEs. While at all observation points the percentage of patients without AEs was 37%-39%, considering all the five scheduled visits, from Day 3 to Day 28, 17% of patients never experienced any AEs, while 48% of patients had four or more concomitant AEs. Patients with no AEs experienced significantly lower pain intensity.
CONCLUSION: Opioid introduction induces various AEs that persist over time and worse patients' symptomatology. Moreover, there seems to be a different expression of the opioid toxicity among patients, and a possible interaction between AEs and the analgesic response. The balance between the opioids analgesic effect and induced toxicity is fundamental in deciding the best management for pain in cancer patients.
AIM: To compare the effects of oral morphine and oxycodone and transdermal fentanyl and buprenorphine on quality of life (QoL) of cancer patients with severe pain.
PATIENTS AND METHODS: Cancer patients with severe pain (NRS 6-10) treated at home and in outpatient clinics who failed to respond to non-opioids and/or "weak" opioids were randomized to morphine, oxycodone, fentanyl, or buprenorphine treatment for 28 days. Immediate-release oral morphine was rescued analgesic and 10-ml lactulose twice daily was prophylaxis of constipation; no antiemetics were used for prophylaxis.
RESULTS: Above all, 62 patients participated and 53 patients completed the study. Good analgesia was obtained with all 4 opioids. Morphine was associated with the less negative impact of pain on the ability to walk and normal work, and tendency on activity (BPI-SF) and lower consumption of rescue morphine. All 4 opioids elicited similar adverse effects. According to ESAS, the intensity of nausea and drowsiness increased at the beginning but decreased as treatment continued. Appetite, well-being, anxiety, depression, and fatigue improved. No changes were seen in constipation, vomiting and dyspnea. Constipation was rarely observed with all opioids (BFI). Any opioids improved overall QoL and emotional functioning with tendency improving physical functioning (EORTC QLQ-C15-PAL). Activity improved (Karnofsky). Morphine induced greater improvement in physical functioning and trend in improvement mood (HADS).
CONCLUSION: All opioids significantly improved patients' QoL. Morphine induced less negative impact of pain on daily activities and greater improvement in physical functioning with trends of better mood and less intense fatigue.
PURPOSE: The aim of the present study was to evaluate the efficacy of an oral formulation of Δ9-tetrahydrocannabinol (ECP002A) in patients with progressive multiple sclerosis (MS).
METHODS: This accelerated proof-of-concept study consisted of 2 phases: a crossover challenge (dose-finding) phase and a 4-week, parallel, randomized, placebo-controlled treatment phase. Twenty-four patients with progressive MS and moderate spasticity were enrolled. During the treatment phase, biomarkers for efficacy and secondary pharmacodynamic effects were measured at baseline and after 2 and 4 weeks of treatment. Serum samples were collected to determine pharmacokinetic properties and perform population modeling. Safety and tolerability profiles were assessed based on adverse events and safety measurements.
FINDINGS: Pain was significantly reduced when measured directly after administration of ECP002A in the clinic but not when measured in a daily diary. A similar pattern was observed in subjective muscle spasticity. Other clinical outcomes were not significantly different between active treatment and placebo. Cognitive testing indicated that there was no decline in cognition after 2 or 4 weeks of treatment attributable to ECP002A compared with placebo. Implications This study specifically underlines the added value of thorough investigation of pharmacokinetic and pharmacodynamic associations in the target population. Despite the complex interplay of psychoactive effects and analgesia, the current oral formulation of Δ9-tetrahydrocannabinol may play a role in the treatment of spasticity and pain associated with MS because it was well tolerated and had a stable pharmacokinetic profile.
BACKGROUND: Hydromorphone is a standard opioid analgesic for cancer pain that, prior to this study, was not approved in Japan, where options for opioid switching are limited. We aimed to investigate the efficacy and safety of hydromorphone (DS-7113b) immediate-release tablets in opioid-naïve cancer patients with moderate to severe cancer pain.
METHODS: Multicenter, active-controlled, randomized, double-blind, parallel-group, non-inferiority study of 183 cancer patients over 20 years of age at 50 clinical sites in Japan. Hydromorphone tablets or oxycodone hydrochloride powder was orally administered four times daily for 5 days. The initial doses of hydromorphone and oxycodone hydrochloride were 4 mg/day and 10 mg/day, respectively, and adjusted as necessary. Efficacy was evaluated as the intergroup difference (95% confidence interval [CI]) of the least squares mean by analysis of covariance, using the baseline visual analog scale (VAS) as a covariate for change in VAS score at treatment completion/discontinuation in the full analysis set.
RESULTS: Non-inferiority of hydromorphone versus oxycodone was confirmed, with an intergroup difference (95% CI) in the least squares mean of -3.4 mm (-9.8 to 3.1 mm) for change in VAS scores, which was below the upper limit of the 95% CI at 10 mm, the non-inferiority limit determined during study planning. Adverse events occurred in 83.0% (73/88) of patients in the hydromorphone group and 77.4% (65/84) in the oxycodone group. The most frequently observed adverse events were somnolence, constipation, vomiting and nausea.
CONCLUSIONS: The efficacy and safety of hydromorphone tablets are equivalent to those of oxycodone immediate-release powder.
OBJECTIVE: To compare efficacy and safety of intravenous continuous infusion of oxycodone with morphine in patients with cancer pain.
METHODS: A 5-day, randomized, open-label, exploratory study at 6 sites in the Republic of Korea. Sixty-six adults aged ≥19 years with moderate-to-severe cancer pain (Numeric Rating Scale [NRS] ≥ 4) were enrolled. The study group received intravenous (IV) oxycodone, and the comparator group received IV morphine which were titrated depending on pain intensity. The efficacy endpoint is change in average NRS score from baseline to Day 5. Other assessments included worst, current, and average pain intensity; patient satisfaction; medication dose; and adverse events.
RESULTS: Both groups achieved >50% reduction in average pain intensity: from "moderate" at baseline (oxycodone versus morphine: 6.0 ± 1.8 versus 5.9 ± 1.4) to "mild" at Day 5 (2.5 ± 1.8 versus 2.8 ± 1.6). While this reduction was similar between groups (3.5 ± 2.2 versus 3.1 ± 1.8, P value = 0.562), oxycodone achieved faster pain relief (average pain: 3.0 ± 1.6 versus 3.9 ± 1.6, P value = 0.020) on Day 2 and significant NRS reductions for worst pain on Day 2 (P value = 0.045) and current pain on Day 2 (P value = 0.035) and Day 5 (P value = 0.020) compared to morphine. Patient satisfaction, adverse events, and adverse drug reactions were similar for both groups.
CONCLUSIONS: For Asian patients with cancer pain, IV oxycodone is faster acting and showed similar analgesic efficacy and safety profiles as IV morphine. This trial is registered with Clinicaltrials.gov NCT02660229.
BACKGROUND & AIMS: Delta-9-tetrahydrocannabinol (THC) is the most abundant cannabinoid from the plant Cannabis sativa. There is only equivocal evidence that THC has analgesic effects. We performed a phase 2 controlled trial to evaluate the analgesic efficacy, pharmacokinetics, safety, and tolerability of an oral tablet containing purified THC in patients with chronic abdominal pain.
METHODS: Sixty-five patients with chronic abdominal pain for 3 months or more (numeric rating scale scores of 3 or more) after surgery or because of chronic pancreatitis were randomly assigned to groups given the THC tablet or identical matching placebos for 50-52 days. Subjects in the THC group were given the tablet first in a step-up phase (3 mg 3 times daily for 5 days and then 5 mg 3 times daily for 5 days), followed by a stable dose phase (8 mg 3 times daily until days 50-52). Preceding and during the entire study period, patients were asked to continue taking their medications (including analgesics) according to prescription. Patients reported any additional pain medications in a diary. Efficacy and safety assessments were conducted preceding medication intake (day 1), after 15 days, and at 50-52 days. Plasma samples were collected on study days 1, 15, and 50-52; mean plasma concentration curves of THC and 11-OH-THC were plotted. The primary end point was pain relief, which was measured by a visual analogue scale (VAS) of the mean pain (VAS mean scores) on the basis of information from patient diaries. Secondary end points included pain and quality of life (determined from patient questionnaires), pharmacokinetics, and safety.
RESULTS: At days 50-52, VAS mean scores did not differ significantly between the THC and placebo groups (F1,46 = 0.016; P = .901). Between the start and end of the study, VAS mean scores decreased by 1.6 points (40%) in the THC group compared with 1.9 points (37%) in the placebo group. No differences were observed in secondary outcomes. Oral THC was generally well-absorbed. Seven patients in the THC group stopped taking the tablets because of adverse events, compared with 2 patients in the placebo group. All (possibly) related adverse events were mild or moderate.
CONCLUSIONS: In a phase 2 study, we found no difference between a THC tablet and a placebo tablet in reducing pain measures in patients with chronic abdominal pain. THC, administered 3 times daily, was safe and well-tolerated during a 50-day to 52-day treatment period. ClinicalTrials.gov number: NCT01562483 and NCT01551511.
AIM OF THE STUDY: To compare analgesia and adverse effects during oral morphine and oxycodone and transdermal fentanyl and buprenorphine administration in cancer patients with pain.
PATIENTS AND METHODS: Cancer patients treated at home and in outpatient clinics with severe pain (numerical rating scale score 6-10) fail to respond to non-opioids and/or weak opioids. All patients were randomized to either morphine, oxycodone, fentanyl or buprenorphine and divided into subgroups with predominant neuropathic and nociceptive pain component. Doses of opioids were titrated to satisfactory analgesia and acceptable adverse effects intensity. Patients were assessed at baseline and followed for 28 days. In all patient groups, immediate-release oral morphine was the rescue analgesic and lactulose 10 mL twice daily was the prophylaxis of constipation; no antiemetics were used as prophylaxis.
RESULTS: A total of 62 patients participated and 53 patients completed the study. Good analgesia was obtained for all 4 opioids, for both nociceptive and neuropathic pain. The use of co-analgesics was greater in patients with neuropathic pain. Morphine treatment was associated with less negative impact of pain on ability to walk, work and activity (trend) according to Brief Pain Inventory-Short Form scores and less consumption of rescue morphine. The most common adverse effects included nausea and drowsiness, which increased at the beginning of the treatment and gradually decreased over the days to come. Appetite, well-being, anxiety, depression, and fatigue improved. There was no constipation (the Bowel Function Index scores were within normal range) during the treatment with all opioids. No changes were seen for constipation, vomiting and dyspnea.
CONCLUSION: All opioids were effective and well-tolerated. Morphine was the most effective in the improvement in some of the Brief Pain Inventory-Short Form items regarding negative impact of pain on patients' daily activities. Prophylaxis of constipation was effective; antiemetics may be considered for nausea prevention.
Objective: The present study aims to explore the effectiveness and safety of low‐dose strong opioids compared with non‐steroidal anti‐inflammatory drugs (NSAIDs) in the treatment of mild cancer pain. Methods: From September 2016 to September 2018, 66 patients with a malignant tumor and mild cancer pain admitted to the Department of Oncology of Dalian Fifth People’s Hospital were divided into the group A (treated with ibuprofen sustained‐release tablets for pain relief) and the group B (treated with oxycodone hydrochloride sustained‐release tablets for pain relief). After 7 days of treatment, the pain relief (Numeric Rating Scale [NRS]), physical strength, quality of life scores (Zubrod/ECOG/WHO [ZPS]), the Edmonton Symptom Assessment System [ESAS], and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Core15‐Palliative [EORTC QLQ‐C15‐PAL] scores), and the occurrence of adverse reactions between the two groups were compared. The occurrence of adverse reactions in the mid‐term (after one month and three months of treatment) between the two groups were also compared. Results: Both groups had over 90% analgesic efficiency, but complete pain relief was more likely to be obtained in the group B (41.18%). The total analgesic efficiency in the group B was higher (100%) than in the group A (98.9%), and the difference was statistically significant (P < 0.05). The differences in the physical strength and quality of life scores in the two groups before and after treatment were statistically significant (P < 0.05). The differences in the ZPS scores between the two groups were statistically significant (P < 0.05). The differences in ESAS and EORTC QLQ‐C15‐PAL scores between groups were not statistically significant (P > 0.05). Conclusion: The application of low‐dose oxycodone hydrochloride sustained‐release tablets as the initial medication for patients with mild cancer pain was safe and effective, and the adverse reactions were easy to manage.
