Maria Teresa Greco

Quality of Cancer Pain Management: An Update of a Systematic Review of Undertreatment of Patients With Cancer

PURPOSE Pain is a frequent symptom in patients with cancer, with substantial impact. Despite the availability of opioids and updated guidelines from reliable leading societies, undertreatment is still frequent. METHODS We updated a systematic review published in 2008, which showed that according to the Pain Management Index (PMI), 43.4% of patients with cancer were undertreated. This review included observational and experimental studies reporting negative PMI scores for adults with cancer and pain published from 2007 to 2013 and retrieved through MEDLINE, Embase, and Google Scholar. To detect any temporal trend and identify potential determinants of undertreatment, we compared articles published before and after 2007 with univariable, multivariable, and sensitivity analyses. RESULTS In the new set of 20 articles published from 2007 to 2013, there was a decrease in undertreatment of approximately 25% (from 43.4 to 31.8%). In the whole sample, the proportion of undertreated patients fell from 2007 to 2013, and an association was confirmed between negative PMI score, economic level, and nonspecific setting for cancer pain. Sensitivity analysis confirmed the robustness of results. CONCLUSION Analysis of 46 articles published from 1994 to 2013 using the PMI to assess the adequacy of analgesic therapy suggests the quality of pharmacologic pain management has improved. However, approximately one third of patients still do not receive pain medication proportional to their pain intensity.

Epidemiology and pattern of care of breakthrough cancer pain in a longitudinal sample of cancer patients: results from the Cancer Pain Outcome Research Study Group.

ObjectiveBreakthrough cancer pain (BTcP) is a frequent event in cancer patients, with a prevalence from 19% to 95%. The reasons for such variability are explained by several factors, including different definitions across studies. In the framework of a wider initiative, we have analyzed the epidemiology of BTcP and identified factors associated with the pattern of care. MethodsThis study reports the results from a multicenter, prospective, nonrandomized, longitudinal study carried out in Italy between 2006 and 2007 on patients with cancer and pain. Transient exacerbations of pain were assessed with 3 different questions, and 1 composite variable to operationally define BTcP was then used as main outcome. After univariate analysis, a logistic model was also fitted to identify prognostic and predictive factors. ResultsOne hundred and ten centers recruited 1801 cases of which 40.3% had BTcP at baseline. Most patients did not receive rescue therapy at the time of study inclusion. Univariate analysis identified several associations with clinical variables. A strong association has been also found with the type of recruiting centers, with oncologic wards reporting a somewhat lower proportion of patients with BTcP (−30%) when compared with palliative centers.Patients with BTcP had a high probability of dying (OR=1.4, 95% CI: 1.1-1.7, P-value 0.006) and to change of the opioid with another for analgesic failure or for side effects (OR=1.4, 95% CI: 1.0-1.9, P-value 0.040) DiscussionThese findings confirm the high prevalence of BTcP and substantial undertreatment and identify a few factors associated with prevalence and prognosis.

An exploratory analysis on the effectiveness of four strong opioids in patients with cancer pain

OBJECTIVE This analysis, carried out in the context of a wider observational prospective study, tried to explore whether four World Health Organization/step-III opioids (morphine, oxycodone, fentanyl, and buprenorphine) had different effectiveness when using several different outcomes and endpoints. DESIGN Cross-sectional and longitudinal design. SETTING Oncologic, palliative, and pain centers in Italy. PATIENTS Two hundred fifty-eight cancer patients monitored over a 3-week follow-up program. Intervention.  Not applicable. OUTCOME MEASURES The analgesic efficacy was assessed using effectiveness endpoints, such as pain intensity, pain intensity difference (PID), proportion of nonresponders (NR) and full-responders (FR) subjects, percentage of switches and dose escalation. RESULTS Mean values of PID led to differences among opioids ranging from 10% to 30%. FR (PID ≥ 30%) were more frequent in buprenorphine-fentanyl-oxycodone groups than in morphine; NR (PID ≤ 0%) were variable. The percentage of switches resulted three times more frequent when using morphine than buprenorphine (24.4% vs 8.6%). An increase of dose ≥ 5% a day was observed in 33.3% of fentanyl patients vs 15% of buprenorphine. As a whole, opioids show some different behaviors on the basis of the considered endpoints. CONCLUSIONS The observed results, even if the small sample size and the nature itself of the study do not allow a definitive evaluation of the effectiveness of the drugs, underline a degree of variability among opioids and address toward a correct planning of a comparative randomized clinical trial that is now underway in Italy. For this reason, a confirmative effectiveness randomized controlled trial is required.

Effects of Transdermal Buprenorphine on Patients-reported Outcomes in Cancer Patients: Results From the Cancer Pain Outcome Research (cpor) Study Group

ObjectivesPain still afflicts most cancer patients, mainly in the metastatic phases, and under-treatment is well documented. Transdermal delivery systems (TDS) containing fentanyl or buprenorphine could potentiality have advantages over oral and parenteral routes, but evidence from comparative trials are scanty. In the framework of a wider initiative, an Outcome Research Study was carried out in Italy in 2006 to evaluate the effects of various analgesic options, particularly buprenorphine TDS. MethodsThis is a multicenter, open-label, prospective, nonrandomized study. Data were collected using a web-based standardized system, with a follow-up up of to 3 months. Pain intensity, the primary outcomes of the study, was measured using 11-point numerical rating scales from the Brief Pain Inventory. ResultsOne-hundred ten centers recruited 1801 cases, most of which (60%) were receiving a strong opioid at the time of inclusion. Of these, 257 had TDS buprenorphine as first choice. Of the remaining 709 patients who at the time of inclusion were not on a strong opioid, 325 changed to a strong opioid and in 43% it was TDS buprenorphine. During the follow-up, physicians had to increase the dosage to control pain (average increase between 16% and 17%). About 34% of patients had an improvement of at least 2 points in worst pain, 15% had a 20% improvement in pain relief, and 40% in satisfaction. Results were in line with those of patients receiving other World Health Organization-level III opioids. ConclusionsDespite the limitations owing to the observational design, these findings may be useful to clinicians to judge the value of the drug under evaluation better and to help researchers design further comparative studies.

Long-term efficacy and safety of oxycodone–naloxone prolonged release in geriatric patients with moderate-to-severe chronic noncancer pain: a 52-week open-label extension phase study

Background Two-thirds of older people suffer from chronic pain and finding valid treatment options is essential. In this 1-yearlong investigation, we evaluated the efficacy and safety of prolonged-release oxycodone–naloxone (OXN-PR) in patients aged ≥70 (mean 81.7) years. Methods In this open-label prospective study, patients with moderate-to-severe noncancer chronic pain were prescribed OXN-PR for 1 year. The primary endpoint was the proportion of patients who achieved ≥30% reduction in pain intensity after 52 weeks of treatment, without worsening bowel function. The scheduled visits were at baseline (T0), after 4 weeks (T4), and after 52 weeks (T52). Results Fifty patients completed the study. The primary endpoint was achieved in 78% of patients at T4 and 96% at T52 (P<0.0001). Pain intensity, measured on a 0–10 numerical rating scale, decreased from 6.0 at T0 to 2.8 at T4 and to 1.7 at T52 (P<0.0001). Mean daily dose of oxycodone increased from 10 to 14.4 mg (T4) and finally to 17.4 mg (T52). Bowel Function Index from 35.1 to 28.7 at T52. No changes were observed in cognitive functions (Mini-Mental State Examination evaluation), while daily functioning improved (Barthel Index from 53.1 to 61.0, P<0.0001). The Screener and Opioid Assessment for Patients with Pain-Revised score at 52 weeks was 2.6 (standard deviation 1.6), indicating a low risk of aberrant medication-related behavior. In general, OXN-PR was well tolerated. Conclusion This study of the long-term treatment of chronic pain in a geriatric population with OXN-PR shows satisfying analgesic effects achieved with a stable low daily dose, coupled with a good safety profile and, in particular, with a reduction of constipation, often present during opioid therapy. Our findings support the indications of the American Geriatrics Society, suggesting the use of opioids to treat pain in older people not responsive to acetaminophen or nonsteroidal anti-inflammatory drugs.

A comparison between the administration of oral prolonged-release oxycodone-naloxone and transdermal fentanyl in patients with moderate-to-severe cancer pain: a propensity score analysis

Background Opioids are the most important pharmacological treatment for moderate-to-severe cancer pain, but side effects limit their use. Transdermal fentanyl (TDF) and oral prolonged-release oxycodone-naloxone (OXN-PR) are effective in controlling chronic pain, with less constipation compared to other opioids. However, TDF and OXN-PR have never been directly compared. Patients and methods Cancer patients with moderate-to-severe chronic pain were consecutively enrolled in two prospective 28-day trials, received either TDF or OXN-PR, and were assessed at baseline and after 7, 14, 21, and 28 days. The primary endpoint was 28-day analgesic response rate (average pain intensity decrease ≥30% from baseline). Other outcome measures included opioid daily dose changes over time; need for adjuvant analgesics; number of switches; premature discontinuation; presence and severity of constipation; and other adverse drug reactions. To compare the efficacy and the safety of TDF and OXN-PR, we used the propensity score analysis to adjust for heterogeneity between the two patient groups. Results Three hundred ten out of 336 patients originally treated (119 TDF and 191 OXN-PR) were included in the comparative analysis. The amount of responders was comparable after TDF (75.3%) and OXN-PR administration (82.9%, not significant [NS]). The final opioid daily dose expressed as morphine equivalent was 113.6 mg for TDF and 44.5 mg for OXN-PR (p<0.0001). A daily opioid dose escalation >5% was less common after OXN-PR (19.3%) than after TDS administration (37.9%, p<0.0001). Opioid switches and discontinuation were similar in both groups. Severe constipation in the two groups was comparable (32.6% after TDF vs 24.7% after OXN-PR, NS). Nausea, vomiting, and dry mouth were significantly less frequent in the OXN-PR group than in the TDF group. Conclusion Despite a similar analgesic activity in moderate-to-severe cancer pain, OXN-PR is characterized by lower daily dosages, less need for drug escalation, and fewer side effects compared to TDF.