Barriers and Adherence to Pain Management in Advanced Cancer Patients.

AIM: To assess patients' barriers to pain management and analgesic medication adherence in patients with advanced cancer. METHODS: This was a prospective cross-sectional study in patients with advanced cancer receiving chronic opioid therapy. Age, gender, cancer diagnosis, Karnofsky level, and educational status were recorded. The Brief Pain Inventory (BPI), Edmonton Symptom Assessment Scale (ESAS), Memorial Delirium Assessment Scale (MDAS), Barriers Questionnaire II (BQ-II), Medication Adherence Rating Scale (MARS), and Hospital Anxiety and Depression Scale (HADS) were the measurement instruments used. RESULTS: One-hundred-thirteen patients were analyzed. The mean age was 68 (±13) years, and 59 (52%) were male. The mean Karnofsky status was 51.4 (standard deviation [SD] 11.5). The mean score for BQ-II items was 1.77 (SD 0.7). The BQ-II score was independently related to the HADS-Depression score (P = 0.033) and the total HADS score (P = 0.049). Negative side-effects and attitudes toward psychotropic medication globally prevailed among MARS items. These items were independently associated with gender (P = 0.030), pain (P = 0.003), and depression (P = 0.047). CONCLUSION: Barriers to pain management were mild. Psychological factors such as depression were the main factor associated with barriers. Poor adherence to analgesic medication was mostly manifested as negative side-effects and attitudes toward psychotropic medication, was more frequent observed in females, and was associated with the ESAS items pain and depression.

Aberrant opioid use behaviour in advanced cancer.

OBJECTIVES: To evaluate the presence of aberrant behaviour in a consecutive sample of patients with advanced cancer treated with opioids in a country like Italy, with its peculiar attitudes towards the use opioids. The second objective was to detect the real misuse of opioids in clinical practice. METHODS: Prospective observational study in two palliative care units in Italy in a period of 6 months. At admission the Edmonton Symptom Assessment Scale, the Memorial Delirium Assessment Scale, Brief Pain Inventory (BPI) and the Hospital Anxiety Depression Scale were measured. For detecting the risk of aberrant opioid use, the Screener and Opioid Assessment for Patients With Pain (SOAAP), the Opioid Risk Tool (ORT), the Cut Down-Annoyed-Guilty-Eye Opener (CAGE) questionnaire adapted to include drug use (CAGE-AID) were used. Aberrant behaviours displayed at follow-up within 1 month were recorded. RESULTS: One-hundred and thirteen patients with advanced cancer were examined. About 35% of patients were SOAPP positive. There was correlation between SOAPP, CAGE-AID and ORT. SOAPP was independently associated with a lower Karnofsky level, pain intensity, poor well-being, BPI pain at the moment. No patient displayed aberrant behaviours, despite having a moderate-high risk. CONCLUSIONS: Despite a high percentage of patients showed a high risk of aberrant behaviours, no patient displayed clinical aberrant behaviours after 1 month-follow-up. This does not exempt from continuous monitoring for patients who are at risk.

Equipotent doses to switch from high doses of opioids to transdermal buprenorphine.

INTRODUCTION: The aim of this study was to evaluate the equianalgesic ratio of transdermal buprenorphine (TD BUP) with oral morphine and TD fentanyl in a sample of consecutive cancer patients receiving stable doses of 120-240 mg of oral morphine or 50-100 microg of TD fentanyl, reporting adequate pain and symptom control. MATERIALS, METHODS, AND RESULTS: Patients receiving daily stable doses of opioids for more than 6 days, with no more than two doses of oral morphine (20 and 40 mg, respectively) as needed, were switched to TD BUP using a fentanyl-BUP ratio of 0.6:0.8 and an oral morphine-BUP ratio of 70:1. Opioid doses, pain and symptom intensity, global satisfaction, and number of breakthrough medication were recorded before switching (T0), 3 days after (T3), and 6 days after (T6). Eleven patients were recruited in a period of 1 year, and data were complete for ten patients. The mean age was 61.6 (SD 9.5), and five patients were males. No significant changes in pain and symptom intensity were found, except improvement in reported constipation (p = 0.014), as well as in global satisfaction with the analgesic treatment. No significant changes in breakthrough pain medication were observed. CONCLUSION: The results of this study suggest that stable patients receiving relatively high doses of oral morphine or TD fentanyl could be safely switched to TD BUP, by using a ratio of 70:1 and 0.6:0.8, respectively, maintaining the same level of analgesia.

Low morphine doses in opioid-naive cancer patients with pain.

Cancer pain can be managed in most patients through the use of the analgesic ladder proposed by the World Health Organization. Recent studies have proposed to skip the second "rung" of the ladder by using a so-called "strong" opioid for moderate pain. However, usual doses of strong opioids commonly prescribed for the third rung of the analgesic ladder may pose several problems in terms of tolerability in opioid-naive patients. The aim of this multicenter study was to evaluate the efficacy and tolerability of very low doses of morphine in advanced cancer patients no longer responsive to nonopioid analgesics. A sample of 110 consecutive opioid-naive patients with moderate-to-severe pain were given oral morphine at a starting dose of 15 mg/day (10 mg in those older than 70 years). Doses were then titrated according to the clinical situation. Pain intensity, morphine doses, symptom intensity, quality of life, and the requirement for dose escalation were monitored for a period of 4 weeks. The treatment was effective and well tolerated by most patients, who were able to maintain relatively low doses for the subsequent weeks (mean dose 45 mg at Week 4). Only 12 patients dropped out due to poor response or other reasons. The use of very low doses of morphine proved to be a reliable method in titrating opioid-naive advanced cancer patients who were also able to maintain their dose, in a 4-week period, below the dose level commonly used when prescribing strong opioids.

Gabapentin for neuropathic cancer pain: a randomized controlled trial from the Gabapentin Cancer Pain Study Group.

PURPOSE: To determine the analgesic effect of the addition of gabapentin to opioids in the management of neuropathic cancer pain. PATIENTS AND METHODS: One hundred twenty-one consecutive patients with neuropathic pain due to cancer, partially controlled with systemic opioids, participated in a multicenter, randomized, double-blind, placebo-controlled, parallel-design, 10-day trial from August 1999 to May 2002. Gabapentin was titrated from 600 mg/d to 1,800 mg/d in addition to stable opioid dose. Extra opioid doses were available as needed. Zero to 10 numerical scale was used to rate average daily pain. The average pain score over the whole follow-up period was used as main outcome measure. Secondary outcome measures were: intensity of burning pain, shooting/lancinating pain, dysesthesias (also scored on 0 to 10 numerical scale), number of daily episodes of lancinating pain, presence of allodynia, and daily extra doses of opioid analgesics. RESULTS: Overall, 79 patients received gabapentin and 58 (73%) completed the study; 41 patients received placebo and 31 (76%) completed the study. Analysis of covariance (ANCOVA) on the intent-to-treat population showed a significant difference of average pain intensity between gabapentin (pain score, 4.6) and placebo group (pain score, 5.4; P =.0250). Among secondary outcome measures, dysesthesia score showed a statistically significant difference (P =.0077; ANCOVA on modified intent-to-treat population = 115 patients with at least 3 days of pain assessments). Reasons for withdrawing patients from the trial were adverse events in six patients (7.6%) receiving gabapentin and in three patients receiving placebo (7.3%). CONCLUSION: Gabapentin is effective in improving analgesia in patients with neuropathic cancer pain already treated with opioids.

Amitriptyline in neuropathic cancer pain in patients on morphine therapy: a randomized placebo-controlled, double-blind crossover study.

AIMS AND BACKGROUND: Amitriptyline is the most common analgesic adjuvant used in cancer patients with neuropathic pain, even though no specific studies have demonstrated a benefit. A randomized placebo-controlled, double-blind crossover study was designed to evidence the effects of amitriptyline in patients with neuropathic cancer pain. METHODS: Sixteen advanced cancer patients with neuropathic pain on systemic morphine therapy, no longer receiving oncologic treatment, presenting moderate pain (about 4 or more, but less than 7, on a numerical scale of 0-10) in the last week, and given a stable morphine dose in the last 2 days were admitted to the study. During the first week of study, patients were administered 25 mg of amitriptyline or equivalent drops of placebo at night for 3 days and 50 mg for the following 4 days. Doses for patients aged more than 65 years were 15 mg (first 3 days) and 30 mg (3 days after). After a week, a crossover took place for the second week, with the other treatment at an inverse sequence. Opioid consumption, pain intensity, symptoms and adverse effects, mood, sleep, patient's preference, quality of life before starting the study, the first week after and the second week after were recorded. RESULTS: No significant benefits in analgesia were found in the global pain intensity of the previous week of treatment, the least pain intensity or the pain evaluated just after a week of treatment, at the moment of the visit, when amitriptyline was compared with placebo. A significant difference was evidenced for the worst pain (P < 0.035). No differences in opioid doses during the period of study were found. Drowsiness, confusion and dry mouth were significantly more intense with amitriptyline than with placebo (P < 0.036, 0.003, and 0.034, respectively). There were no substantial differences between the two treatments in Spitzer's quality of life score and for each item. No differences in patients' preference for the two treatment periods were found. The analgesic effects of amitriptyline were slight and associated with adverse effects. CONCLUSIONS: In light of the results obtained in the study, the extensive use of the drug for cancer pain should be questioned.

When the progression of disease lowers opioid requirement in cancer patients.

OBJECTIVE: To describe 2 cases in which an abrupt progression of disease compromising pain pathways and inducing some relief of existing pain or limiting drug delivery to central nervous system. METHODS: Case reports which a significant decrease of opioid requirement was reported, either systematically and spinally. RESULTS: The progression of disease produced changes in pain input or limited the effects of opioids given spinally. DISCUSSION: The data presented suggest that physicians should be aware of the possibility that opioid doses have to be reduced, where presumably specific events related to the progression of disease can change the pain syndrome or reduce the delivery of opioids when using particular routes of administration. This problem needs to be recognized and treated appropriately when it occurs.

Morphine versus oxycodone in pancreatic cancer pain: a randomized controlled study.

OBJECTIVE: According to experimental findings, oxycodone (OX) could have some advantages over morphine (MO) in clinical models of visceral pain. It was hypothesized that OX could have some advantages over MO in terms of efficacy and dose escalation in pancreatic cancer pain. METHODS: Sixty patients with pancreatic cancer with a pain intensity rating of 4/10 who required opioids were included in the study. Patients were randomized to receive 30 mg/d of sustained release oral MO or sustained release oral OX (20 mg/d). Opioid doses were increased according to the clinical needs. Daily doses of opioids, pain and symptom intensity were recorded at admission (T0) and at weekly intervals for the subsequent 4 weeks (T1, T2, T3, and T4), with an extension at 8 weeks (T8). Opioid escalation index (OEI) as percentage (OEI %) and in mg (OEI mg) was calculated. RESULTS: Nineteen and 20 patients in groups OX and MO, respectively, were followed for the entire period of study (T4). No differences between groups were found in age (P=0.400), Karnofsky (P=0.667), or escalation indexes at T4 and T8 (OEImg, P=0.945 and OEI %, P=0.295). No statistical differences in pain and symptoms intensity between the groups were observed. CONCLUSION: OX and MO provided similar analgesia and adverse effects with similar escalating doses in patients with pancreatic cancer pain, resembling observations reported in the general cancer pain population. The experimental hypothesis that OX would be superior to MO in the clinical model of pancreatic cancer pain was not confirmed.

Low doses of transdermal buprenorphine in opioid-naive patients with cancer pain: a 4-week, nonrandomized, open-label, uncontrolled observational study.

OBJECTIVE: The aim of this study was to evaluate the effect and tolerability of low doses of transdermal (TD) buprenorphine patches in opioid-naive patients with cancer pain. METHODS: This was a nonrandomized, open-label, uncontrolled study in consecutive opioid-naive patients with advanced cancer and moderate pain. TD buprenorphine was initiated at a dose of 17.5 microg/h (0.4 mg/d), with patch changes every 3 days. Doses were then adjusted according to the clinical response. Pain intensity, opioid-related adverse effects, TD buprenorphine doses, and quality of life were monitored over 4 weeks. The time to dose stabilization and indexes of dose escalation were also calculated. RESULTS: Thirty-nine consecutive patients completed all 4 weeks of the study. Low doses of TD buprenorphine were well tolerated and effective in these opioid-naive patients with cancer pain. Pain control was achieved within a mean of 1.5 days after the start of TD buprenorphine therapy. The mean TD buprenorphine dose was significantly increased from baseline beginning at 2 weeks after the start of therapy and had doubled by 4 weeks (P < 0.05). Pain intensity was significantly decreased from baseline beginning at 1 week and continuing through the remaining weekly evaluations (P < 0.05). The mean buprenorphine escalation index, calculated as a percentage and in milligrams, was 41.2% and 0.2 mg, respectively. Quality of life improved significantly over the study period (P = 0.007). There were no significant changes in opioid-related symptoms between weekly evaluations. CONCLUSION: Observations from this study suggest that randomized, controlled, double-blind studies of TD buprenorphine 17.5 microg/h in opioid-naive patients with cancer pain may be warranted.

Randomized double-blind, double-dummy crossover clinical trial of oral tramadol versus rectal tramadol administration in opioid-naive cancer patients with pain.

Tramadol is commonly used as second step drug of the analgesic ladder. In circumstances where the oral route is unavailable, rectal administration of opioids might be a simple alternative. The aim of this study was to compare the analgesic activity and tolerability of tramadol by oral and rectal administration in a double-blind, double-dummy crossover trial. The study included 60 cancer patients with cancer pain no longer responsive to non-opioid drugs. Each patient initially received oral tramadol 50 mg (drops), followed by tramadol sustained release 100 mg orally, and placebo rectally, or tramadol 100 mg rectally and placebo orally, twice a day, in a randomized sequence, on each of 3 days. Patients were allowed to take 50 mg of oral tramadol by drops as needed (four doses per day, to a maximum of 400 mg/day, including the basal dose given by the oral or rectal route). Pain intensity and relief and symptom scores were recorded every day and at the end of each phase of the crossover. The mean age of the patients was 66.1 years (SD 13.5 years); 36 were female, and 44 completed both periods. Patients dropped out due to adverse effects (15 patients) and refusal (1 patient). No differences in the use of rescue dose of oral tramadol were observed between the groups. No differences in pain intensity and relief scores, or in other symptoms between the two treatments were observed. No differences in treatment efficacy as judged by the clinician (P=0.73), in patient compliance (P=0.35), or in patient satisfaction regarding treatment (P<0.35) were found. No differences in adverse effects were found between the two treatments (25.5%, 13 patients, and 20.4%, 11 patients, with oral and rectal treatment, respectively). The proportion of preferences favored oral administration for both physicians (P=0.0002) and patients (P=0.002). Rectal administration of tramadol appears a reliable, noninvasive alternative method of pain control for patients no longer responsive to non-opioid analgesics, unable to take oral tramadol.