OBJECTIVE: To assess the efficacy, safety and impact on quality of life of tramadol in the treatment of neuropathic pain in patients with cancer.
METHODS: Patients with similar characteristics were grouped in pairs and randomised to receive either tramadol or placebo. The initial tramadol dosage was 1 mg/kg every 6 hours, increasing to 1.5 mg/kg every 6 hours if necessary to control pain.
RESULTS: The study enrolled 36 patients (22 women, 14 men), with a mean age of 50 years. In the group receiving tramadol (n = 18), major improvements in pain intensity and Karnofsky scores occurred (p < 0.001), sleep quality improved by day 45 (p < 0.05) activities of daily living improved (p < 0.05), and use of analgesics that had been taken before the study was reduced (p < 0.05) compared with the placebo group. There was no difference between the groups with regard to changes in the Zung Depression Scale, Beck Anxiety Inventory scores and neurophysiological assessments. More patients in the tramadol group experienced adverse events (p < 0.05). The most common adverse events were nausea, vomiting and constipation.
CONCLUSIONS: Tramadol is a therapeutic option for the control of neuropathic pain in patients with cancer, and appears to improve quality of life in these patients. The analgesic effect of tramadol is independent of changes in anxiety, depression and nervous system function.
PURPOSE: To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain.
PATIENTS AND METHODS: Patients in international palliative care clinics with pain requiring initiation of strong opioids were randomly assigned to receive methadone (7.5 mg orally every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained release every 12 hours and 5 mg every 4 hours as needed). The study duration was 4 weeks.
RESULTS: A total of 103 patients were randomly assigned to treatment (49 in the methadone group and 54 in the morphine group). The groups had similar baseline scores for pain, sedation, nausea, confusion, and constipation. Patients receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those receiving morphine (three of 54; 6%; P =.019). The opioid escalation index at days 14 and 28 was similar between the two groups. More than three fourths of patients in each group reported a 20% or more reduction in pain intensity by day 8. The proportion of patients with a 20% or more improvement in pain at 4 weeks in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups.
CONCLUSION: Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain.
OBJECTIVE: This randomised, multicentre, direct open comparative trial evaluated the efficacy, treatment convenience, tolerability and safety aspects of transdermal therapeutic system (TTS)-fentanyl and sustained-release oral morphine (SRM) in both opioid-naïve patients with moderate-to-severe cancer-related pain and in patients who had already been using opioids for mild-to-moderate pain. The two treatment groups were run in parallel. Special attention was paid to constipation, nausea/vomiting, drowsiness and respiratory depression.
PATIENTS AND METHODS: The 131 enrolled patients started the 4-week treatment at low doses of opioid (25 microg/h TTS-fentanyl for 3 days or 30 mg SRM every 12 h) and were individually titrated. Tolerability, efficacy and safety were assessed throughout the study period. Frequency of constipation was the primary study variable and accordingly the study was powered for this. Both patients and investigators made a global treatment evaluation.
RESULTS: TTS-fentanyl and SRM were shown to be equally effective. Pain control and sleep quality improved with both treatments. None of the patients developed respiratory depression. Statistically significantly more patients in the SRM treatment group discontinued the trial prematurely (59% vs 27%; p < 0.001), particularly due to adverse events (36% vs 4%; p < 0.001). Fewer patients in the TTS-fentanyl than in the SRM treatment group reported constipation during the trial. This finding was statistically significant after 1 week of treatment (27% vs 57%; p = 0.003). The favourable tolerability profile of TTS-fentanyl was also reflected in both the patient and the investigator global evaluation of the treatment. Patient assessment favoured TTS-fentanyl treatment in terms of a significantly lower rate of troublesome side-effects ('quite a bit' to 'very much' troublesome side-effects in 14% vs 36% of patients; p = 0.003) and less interruption of daily activities (absence of any interruption of daily activities in 88% vs 63% of patients; p = 0.012). Investigators scored TTS-fentanyl as significantly better with respect to 'side-effects' (p = 0.039) and 'overall impression' (p = 0.013). Sub-analyses of opioid-naïve users gave similar results.
CONCLUSION: These data indicate that TTS-fentanyl, when used as an opioid of first choice in the treatment of cancer-related pain, is as effective as, but better tolerated than, SRM, including in opioid-naïve patients.
AIMS OF THE STUDY: To assess the analgesic efficacy and side effects of tramadol and equianalgesic doses of morphine and to assess the quality of life (QL) in patients suffering from cancer pain and to establish equianalgesic doses of oral tramadol
and morphine. PATIENTS AND METHODS: Fourty opioid-naive patients with moderate, strong or very strong cancer pain (verbal scale) or at least 45 mm on VAS scale, were treated with tramadol (20 patients) or morphine (20 patients). During the first 7 days the pain was stabilised by the use of immediate release forms of tramadol (drops, capsules) or morphine (water solution). After 7 days, if a satisfactory pain relief was achieved and appropriate daily doses were applied (tramadol 150-600 mg, morphine 20-200 mg) patients were switched to controlled release forms of tramadol – Tramal Long (Retard) tablets – or sustained release morphine (MST Continus tablets or M-eslon capsules) for 28 days. QL was assessed by QLQ C 30 questionnaire. Pain intensity was appraised by VAS and verbal scale, side effects by verbal scale. RESULTS: The duration of treatment was 3-310 (mean 87.15±78.23) days for Tramal Retard and 5-502 (mean 100.05±102.67) days for morphine MST Continus and M-eslon. Daily doses were as follows: 200- 600 (mean 322.22±116.60) mg for tramadol and 20-270 (123.5±78.15) mg for morphine. Satisfactory analgesia was achieved in both groups. However, in patients with neuropathic pain better analgesic effect was noted in the morphine group (significant difference in VAS scale after first week of the treatment). 80% of patients in both groups preferred the treatment with controlled release forms of tramadol and morphine. The treatment was well tolerated, 17 patients in tramadol group and 18 in morphine group completed the study. More side effects were noted in morphine group, however significant differences appeared only in drowsiness, difficulties in passing urine, sweating and dizziness intensity. QL results revealed better global QL and less fatigue after 35 days of the tramadol treatment. CONCLUSIONS: Tramadol and equianalgesic doses of morphine (up to 270 mg/day) in immediate and controlled release forms are effective in the treatment of different types of moderate and severe cancer pain. Tramadol is less effective in patients with neuropathic pain. Both drugs can be safely used at home. Better global QL and less fatigue was observed after 35 days of the tramadol treatment. Tramadol is recommended in patients with moderate pain (VAS 30-54 mm) and morphine in patients with severe and very severe pain (VAS >54 mm). Equianalgesic doses of tramadol and morphine administered orally are 4:1.
PURPOSE: The aim of this study was to evaluate the analgesic and adverse effects and the doses of methadone in comparison to morphine.
PATIENTS AND METHODS: A prospective randomized study was performed in a sample of 40 patients with advanced cancer who required strong opioids for their pain management. Patients were treated with sustained-release morphine or methadone in doses titrated against the effect administered two or three times daily according to clinical need. Opioid doses, adjuvant medications, symptoms associated with opioid therapy, pain intensity, and pain mechanisms were recorded. The opioid escalation indices in percentage (OEI%) and milligrams (OEImg) were calculated. The effective analgesic score (EAS) that monitors the analgesic consumption-pain ratio was also calculated at fixed weekly intervals.
RESULTS: differences in pain intensity were found. Patients treated with methadone reported values of OEI significantly less than those observed in patients treated with morphine. Seven patients in the methadone group maintained the same initial dosage until death, whereas only one patient in the morphine group did not require opioid dose escalation. A more stable analgesia in time in patients treated with methadone was shown by the low number of gaps in EASs reported. Symptom frequencies and intensities were similar in the two groups.
CONCLUSION: Methadone is a drug of indisputable value in the treatment of cancer pain, and an unbalanced focus on the risks of inappropriate use rather than the benefits should not compromise the use of a relevant alternative to morphine in the management of cancer pain.
The transdermal therapeutic system (TTS) for fentanyl is a drug-delivery system for use in patients with chronic pain who require an opioid analgesic. A multicentre, randomized, double-blind, placebo-controlled study was performed to evaluate the efficacy and safety of TTS-fentanyl as an analgesic for chronic cancer pain. One hundred and thirty-eight patients entered a 15-day dose-titration period, followed by a 9-day double-blind period (95 patients) with TTS-fentanyl or placebo. Fifty-five patients entered a follow-up period of indefinite duration. For the majority of patients, TTS-fentanyl 50-75,μg/h provided effective analgesia. Due to an unexpectedly high placebo response, it was not possible to show fentanyl to be statistically superior to placebo at the 5% significance level. Nine patients treated with fentanyl and 13 treated with placebo were withdrawn from the study during the double-blind therapy because of insufficient efficacy (not significant), while 66% of fentanyl-treated patients experienced effective pain control compared with 48% of placebo-treated patients (p = 0.071). During the course of the double-blind therapy, the mean dose of rescue morphine increased slightly more in the placebo group than in the fentanyl group. At the end of the double-blind phase, the investigators rated trial medication as being 'good' or 'excellent' in 30 patients in the fentanyl group and 23 in the placebo group. TTS-fentanyl appeared to be well tolerated, with a low incidence of constipation, somnolence and nausea. Due to an unexpectedly high placebo response it was not possible to demonstrate fentanyl to be statistically superior to placebo. This may reflect the practical difficulties of performing clinical trials in cancer patients with great inter-individual variability. (PsycINFO Database Record (c) 2016 APA, all rights reserved)
BACKGROUND: The use of oxycodone to treat chronic cancer pain has been hampered by its short elimination half-life, which necessitates administration every 4 hours. This study compared the clinical efficacy and safety of a novel oxycodone formulation with that of hydromorphone in the treatment of cancer pain.
METHODS: In a double-blind crossover study, 44 patients with stable cancer pain were randomized to controlled-release oxycodone or controlled-release hydromorphone, each given every 12 hours for 7 days. Pain intensity, nausea, and sedation were assessed by patients four times daily, and breakthrough analgesia was recorded.
RESULTS: Thirty-one patients completed the study (18 women, 13 men; mean age, 56 +/- 3 years) and received a final controlled-release oxycodone dose of 124 +/- 22 mg per day and a final controlled-release hydromorphone dose of 30 +/- 6 mg per day. There were no significant differences between treatments in overall Visual Analogue Scale (VAS) pain intensity (VAS 28 +/- 4 mm vs. 31 +/- 4 mm), categorical pain intensity (1.4 +/- 0.1 vs. 1.5 +/- 0.1), daily rescue analgesic consumption (1.4 +/- 0.3 vs. 1.6 +/- 0.3), sedation scores (24 +/- 4 mm vs. 18 +/- 3 mm), nausea scores (15 +/- 3 mm vs. 13 +/- 3 mm), or patient preference. Two patients experienced hallucinations on controlled-release hydromorphone, but none did while receiving controlled-release oxycodone.
CONCLUSIONS: Controlled-release oxycodone demonstrated excellent pharmacodynamic characteristics, analgesic efficacy, and safety as compared with controlled-release hydromorphone and represents an important new therapeutic option for cancer pain management.
Cancer patients requiring strong opioid analgesia (n = 202; mean age, 61.5 years; range, 18-89 years; 55% men) were recruited from 38 United Kingdom palliative care centers into a randomized, open, two-period, crossover study comparing transdermal fentanyl with sustained-release oral morphine. Patients received one treatment for 15 days followed immediately by the other for 15 days. Daily diaries were completed. Both treatments appeared equally effective in terms of pain control, as assessed by the Memorial Pain Assessment Card and European Organization for Research and Treatment of Cancer (EORTC) pain scores. Fentanyl was associated with significantly less constipation (p < 0.001) and less daytime drowsiness (p = 0.015) but greater sleep disturbance (p = 0.004) and shorter sleep duration (p = 0.008) than morphine. The World Health Organization (WHO) performance status and EORTC global quality of life scores showed no significant difference between treatment groups. Of those patients who were able to express a preference (n = 136), significantly more preferred the fentanyl patches (p = 0.037). We conclude that, in this study, transdermal fentanyl provided pain relief that was acceptable to cancer patients and was associated with less constipation and sedation than morphine. These reduced side effects may contribute to patients preference for the patches.
BACKGROUND: Controlled-release morphine (MST) given twice daily provides a simpler and more convenient treatment regimen than 4-hourly opioid administration for the control of cancer pain. Recently, a new formulation of transdermal fentanyl (TDF) has been developed which provides a new route for the treatment of cancer pain. The present study was designed to compare the analgesic efficacy, safety and adverse effects of MST and TDF in the management of chronic cancer pain.
METHODS: In this open, comparative and randomized study, patients were treated with oral morphine hydrochloride immediate-release (MHIR) in the stabilization phase and then the prescription was switched to MST or TDF for 14 days in the treatment phase. Oral MHIR was provided as rescue medication for breakthrough pain. Assessments of the pain intensity, pain frequency, degree of pain improvement, profile of mood states, quality of sleep, activity status and adverse effects were performed before and after the stabilization phase and before and after the treatment phase.
RESULTS: Forty of 47 cancer patients completed the study with 20 patients in each group. There were significant (p < 0.05) improvements in pain intensity, pain frequency, mood states and quality of sleep in both groups before and after treatment, while improvement in the activity status was not significant. No specific adverse effects were encountered except for drowsiness which occurred in 6 patients treated with MST and 5 treated with TDF (p < 0.05). Insomnia was significantly improved (p < 0.05) with both regimens compared with that in the period before treatment. There were no significant differences between the two study groups in analgesic efficacy or adverse effects.
CONCLUSIONS: These results suggest that TDF and MSt are safe and effective analgesics for the management of chronic cancer pain. However, TDF provides a simpler and more convenient treatment for those patients with severe nausea, vomiting or dysphagia.
To assess the efficacy, safety and impact on quality of life of tramadol in the treatment of neuropathic pain in patients with cancer.
METHODS:
Patients with similar characteristics were grouped in pairs and randomised to receive either tramadol or placebo. The initial tramadol dosage was 1 mg/kg every 6 hours, increasing to 1.5 mg/kg every 6 hours if necessary to control pain.
RESULTS:
The study enrolled 36 patients (22 women, 14 men), with a mean age of 50 years. In the group receiving tramadol (n = 18), major improvements in pain intensity and Karnofsky scores occurred (p < 0.001), sleep quality improved by day 45 (p < 0.05) activities of daily living improved (p < 0.05), and use of analgesics that had been taken before the study was reduced (p < 0.05) compared with the placebo group. There was no difference between the groups with regard to changes in the Zung Depression Scale, Beck Anxiety Inventory scores and neurophysiological assessments. More patients in the tramadol group experienced adverse events (p < 0.05). The most common adverse events were nausea, vomiting and constipation.
CONCLUSIONS:
Tramadol is a therapeutic option for the control of neuropathic pain in patients with cancer, and appears to improve quality of life in these patients. The analgesic effect of tramadol is independent of changes in anxiety, depression and nervous system function.
