Opioid Rotation in Cancer Pain Treatment
A systematic review
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Background: Rotating several different WHO level III opioid drugs is a therapeutic option for patients with chronic cancer-related pain who suffer from inadequate analgesia and/or intolerable side effects. The evidence favoring opioid rotation is controversial, and the current guidelines in Germany and other countries contain only weak recommendations for it.
Methods: This review is based on pertinent publications retrieved by a systematic review of the literature on opioid rotation for adult patients with chronic cancer-related pain who are regularly taking WHO level III opioids by the oral or transdermal route.
Results: 9 individual studies involving a total of 725 patients were included in the analysis, and 3 previous systematic reviews of studies involving a total of 2296 patients were also analyzed. Morphine, oxycodone, fentanyl, hydromorphone, and buprenorphine were used as first-line opioid drugs, and hydromorphone, buprenorphine, tapentadol, fentanyl, morphine, oxymorphone, and methadone were used as second-line opioid drugs. In all of the studies, pain control was achieved for 14 days after each rotation. In most of them, the dose of the new drug introduced in each rotation needed to be increased above the dose initially calculated from a rotation ratio, with the exception of rotations to methadone. The frequency of side effects was only rarely lessened, but patients largely considered the result of opioid rotation to be positive. No particular opioid drug was found to be best.
Conclusion: Opioid rotation can improve analgesia and patient satisfaction. The success of opioid rotation appears to depend on the magnitude of the initial dose, among other factors. Tables of equianalgesic doses should be considered no more than a rough guide for determining the dose of the new drug. Rotations to methadone should be carried out under clinical supervision in experienced hands.
Pain is experienced by 50 to 90% of cancer patients (1). It is estimated that adequate pain relief can be achieved in 71 to 100% of cases if the “WHO analgesic ladder” for cancer pain is used (2). Nevertheless, around 30% of patients treated with powerful opioids still have pain, opioid-associated adverse drug reactions, or both (3). The term opioid rotation describes the change from one drug (“first-line opioid”) to another (“second-line opioid”) owing to intolerable adverse events accompanying adequate analgesia or to increasing side effects when the opioid dose is increased because of inadequate pain relief (4, 5). There are limited opportunities for dose escalation, because the risk of opioid-associated mortality increases sharply at morphine equivalent daily doses over 100 mg (6).
The terms opioid rotation and opioid switch are largely used synonymously in the literature. It should be noted that authors do not always distinguish rotation for the reasons outlined above from rotation on grounds of “convenience.” The latter is more correctly referred to as opioid conversion and may take place, for example, because the patient prefers a particular preparation although stable analgesia without side effects has already been achieved.
In principle opioid rotation can also be used to alleviate non-cancer pain, but in practice it plays a much smaller part, particularly since the publication of the LONTS guideline in Germany (7). According to the literature opioid rotation is necessary in 20 to 44% of cancer pain patients and can lead to clinical improvement in 40 to 80% of cases (8, e1).
Following a Cochrane review in 2004, only two further systematic reviews of the efficacy of opioid rotation specifically in cancer pain patients appeared up to 2010 (9, 10). The authors of all three publications came to the conclusion that although opioid rotation is widely practiced, robust evidence is lacking due to the mainly methodological limitations of the studies concerned. The dose equivalents listed in Table 1 are commonly used in clinical practice and form the basis of various guideline recommendations.
The mostly cautious nature of the recommendations in guidelines (Box) makes it clear that considerable uncertainty prevails in the practice of opioid rotation for the management of cancer pain.
The aim of this review is therefore to provide an update on opioid rotation in cancer-related chronic pain by means of a systematic survey of publications with a high level of evidence.
The systematic literature search was oriented on the recommendations of the PRISMA Statement (11) and the rules of the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF) for the formulation of guidelines (e6).
A Cochrane review by Quigley (8), published in 2004, systematically examined the primary literature on opioid rotation for treatment of pain from 1960 to January 2003. We carried out a systematic search for aggregated evidence published thereafter (January 2003 to January 2017) in DARE (Database of Abstracts of Reviews of Effects) and MEDLINE (PubMed). Inspection and evaluation of the aggregated evidence revealed one high-quality systematic review published by Dale et al. in 2011 (10) (search period for primary literature 2003 to 2010). Based on the search strategy in that review, we defined a sensitive strategy for searching the databases MEDLINE (via PubMed) and CENTRAL (Central Register of Controlled Trials). Furthermore, we carried out a hand search of the major German and international journals. The detailed search strategy for all databases is presented in eTable 1.
Abstracts of the publications found in all sources were initially screened for relevant content. The research question was formulated in PICO format (Table 2).
Study selection: inclusion/exclusion criteria
Two reviewers (MS and FH) read the full text of all articles identified as potentially relevant on abstract screening for a priori defined inclusion and exclusion criteria regarding content and methods (eTable 2). With regard to study design, we included systematic reviews (SRs) with or without meta-analysis, randomized controlled trials (RCTs), and prospective observational studies (with or without a control group). Narrative/nonsystematic reviews, retrospective observational studies, case series, and individual case reports were excluded.
Data extraction and evaluation
The central clinical and methodological data of all included studies are reported in evidence tables stratified by study design (SRs: eTable 3, RCTs and prospective observational studies: eTable 5).
Quality assessment of the included systematic reviews and studies
The risk of bias (RoB) in the included RCTs was assessed by two independent reviewers using the validated Cochrane Risk of Bias Tool (14).
The study quality of the prospective observational studies was judged with the aid of the validated MINORS assessment instrument (Methodological Index for Non-randomized Studies) (15).
Classification of the evidence
In addition to quality assessment of the included publications, the SRs and individual studies were classified according to the Oxford Centre for Evidence-Based Medicine (CEBM) levels of evidence LoE 1a to LoE 5 (16).
Altogether, the database survey and hand search identified 502 publications, 12 of which satisfied our inclusion criteria: three SRs (9, 10, 17), four RCTs (18–21), and five prospective observational studies without a control group (22–26). For the sake of completeness, the results of two SRs identified during the search for aggregated evidence in the years 2003 to 2010 were tabulated (8, 27). None of the reviews had performed a meta-analysis of the individual studies’ results. Three of the five identified SRs had explicitly followed the PRISMA Statement. On the basis of the AMSTAR criteria, the methods of all reviews except one were classed as high quality and together with the primary literature represent evidence level 3a.
Results of the systematic reviews
The 2011 review by Dale (10), conceived as a follow-up to Quigley’s Cochrane review (8), included 11 uncontrolled prospective studies (n = 280) of various opioids with low numbers of cases (n = 10 to 32). With regard to pain, seven studies reported a reduction of >3/10 points on the numeric rating scale (NRS). Three studies expressed the amelioration of pain as a success rate of 50 to 80%; however, the measurement criteria were inconsistent. No advantage could be discerned for any individual substance, but the success of rotation was associated with the dose intensity of the first-line opioid. The authors concluded that higher dosage tended to lead to lower success of rotation. Most studies did not report whether there had been adequate titration of the primary opioid or whether the follow-up period after rotation had been sufficiently long. The authors reasoned that observation for at least 14 days after rotation is necessary to obtain meaningful data.
The SR of 10 prospective studies (including one RCT, n = 42) and 15 retrospective studies (n = 1229) by McLean (17) examined rotation to methadone and took a look at various rotation regimens (Table 4). However, only in 17 of these studies were the endpoints ascertained by means of validated instruments; in the remaining eight studies they were established by clinical assessment alone. While pointing out methodological limitations, the authors stated that the result of rotation was rated positive in almost all studies. Both the ad libitum approach and the 3-day switch method were judged successful in over 90% of patients, but this was the case for only 78% of patients in whom the rapid conversion technique was used.
Mercadante and Caraceni (9) conducted an SR of 5 RCTs and 26 prospective case series (n = 1887) with the aim of verifying the evidence level of equianalgesic dose recommendations. This SR formed the basis for the recommendations in Table 1, but also found clear-cut dependence on the dose intensity of the first-line opioid: the higher the dose, the less likely was successful rotation without dose adjustment, while the data in Table 1 for oxycodone, hydromorphone, fentanyl, and buprenorphine in lower dosage proved reliable. The authors did not specify a cut-off value for a first-line opioid dose below which the recommendations in the table should be followed. They explicitly gave no equianalgesic recommendation for rotation to methadone due to the large variance of results.
Results of the individual studies
In six of the nine individual studies included (total n = 725), opioid rotation had been carried out because of pain or intolerable side effects, while in the other three studies analgesia was stable and the reason for rotation was purely for convenience (eTable 5).
With regard to the primary endpoint, all of the studies showed amelioration of pain (if that was the reason for rotation) or continuation of stable pain relief (if the intervention was performed on grounds of convenience).
All of the studies featured dose titration phases to achieve stable analgesia, and in all of them one or more dose adjustments were made in the follow-up period to attain the endpoint. The first-line opioid dose differed considerably between studies with patients who were switching for convenience (MEDD 33 to 92 mg) and those in which the patients had inadequate analgesia and/or intolerable side effects (MEDD 124 to 1330 mg). In the majority of studies the dose of the second-line opioid was increased in the course of the follow-up period after rotation (Table 3). Only Moksnes (19), who rotated to methadone using the stop-and-go method (SAG) or the 3-day switch (3DS), found a reduction in the equivalent dose of methadone at the end of the 14-day observation phase. In the study by Poulain (20) the methadone dose remained stable with no great variation during the observation period.
Opioid-related side effects were described in all studies, although the criteria and the instruments used for measurement were heterogeneous. The stated proportions of patients with adverse effects varied from 25% and 33% for Poulain (20) to >90% in the studies by Slatkin (21), Imanaka (18), and Lee (22). Two studies found no difference in the rate of side effects before and after rotation (20, 24). In their convenience study, Imanaka et al. (18) described superiority of tapentadol over morphine (38 % versus 54 %) with regard to the occurrence of gastrointestinal adverse effects. The remaining side effects were comparable in the two groups. In another convenience population, Minami et al. (25) found an amelioration of oxycodone-associated fatigue after rotation to fentanyl while other adverse effects were comparable. None of the studies of patients with pain or intolerable side effects revealed any advantage for a specific substance.
Three studies investigated the patients’ subjective satisfaction. The highest rate (96%) was reported by Slatkin; at the same time, 93% of the patients stated they had experienced at least one new undesired effect following rotation (21). In two other studies (22, 25) with rotation from oxycodone to hydromorphone (n = 114, rotation due to pain) and from oxycodone to fentanyl (n = 49, rotation for convenience), around 60% of patients were satisfied with the results 14 days after rotation.
Applicability of equianalgesic conversion charts
Once the decision to switch opioids has been made, the dose of the second-line opioid must be selected for safety as well as efficacy. If the change is being made because of insufficient analgesia, intolerable side effects, or both, guidelines recommend that the new dose should be lower than calculated at first, then titrated upward after rotation (8). In the studies investigated here, however—with the exception of those on methadone—the initially calculated dose of opioid had to be increased to achieve adequate analgesia, regardless of the indication for rotation (Table 3). In this regard, McLean et al. (17) point out that precisely in patients who are clinically unstable or experiencing exacerbated pain, one should consider giving a higher dosage of the second-line opioid from the very beginning, to avoid the risk of persisting undertreatment. High dosage of the first-line opioid may reflect a complex pain situation and have an important effect on the success of rotation (24).
Special features of the clinical deployment of methadone
A variety of methods are used for rotation to methadone (Table 4). The 3-day switch and ad libitum methods seem effective, despite weak evidence, while models that attempt swift rotation (stop and go, rapid conversion) appear to yield no advantage (17). Owing to the long half-life, the time required to achieve dose stability varies from 35 to 325 h (13.5 days). The higher the dosage of the first-line opioid, the greater is the effect of the methadone. Therefore, a comparably low dosage of methadone is used in rotations from high-dose first-line opioids (Table 4). Moreover, high initial doses (≥ 40 mg/day) and rapid increases (>25 mg/day) are classed as risky (28). Therefore, regardless of the method selected one should follow the EAPC guideline recommendation (e1) and monitor the patient during the opioid rotation.
Opioid-associated adverse drug reactions
Gastrointestinal side effects are among the most frequently occurring adverse drug reactions associated with opioid intake. In particular, obstipation affects 41 to 73% of cancer patients treated with opioids (37). In cases of refractory obstipation, guidelines (16) recommend, among other options, rotation to fentanyl or methadone. Combination of opioids with naloxone is also thought to be beneficial by decreasing the effect on µ-receptors (38), and studies of patients with non-cancer pain have shown that administration of tapentadol is helpful in the presence of gastrointestinal side effects (39, 40). This was confirmed in a comparative study in which 100 patients rotated to either tapentadol or morphine (18): the rate of gastrointestinal adverse effects was much lower in the tapentadol group than in those who switched to morphine.
The systematic reviews included in this study displayed considerable heterogeneity with regard to their methods, the nature of the studies they covered, their choice of endpoints, and their assessment of the individual studies analyzed. Despite a sensitive, systematic search for primary literature we identified only a small number of randomized controlled trials. One general problem in the conduct of clinical studies on patients with pain is that for ethical reasons it is difficult or impossible to include those suffering from uncontrolled pain or adverse drug reactions in studies of that nature (27), and this restricts the data available. Furthermore, our hand search and database survey principally brought up studies that demonstrated the efficacy of opioid rotation while simultaneously having high drop-out rates. Publication bias is likely.
A further limitation of the individual studies included in our analysis is the high potential for bias in documentation of the endpoints. Although pain and side effects are often measured with standardized instruments (numerical/verbal rating scales), they are reported by the patients and are thus subjective endpoints vulnerable to bias. Just as vulnerable are the treating physicians’ estimations of the endpoints in the absence of blinding. There was particularly pronounced variation in the interpretations placed on the commonly used terms “effective” and “successful.” The real “success” of opioid rotation is therefore difficult to assess, very hard to compare, and above all should not be evaluated too early. According to Dale (10) the observation period should not be less than 14 days.
The conversion ratios for the attainment of effective analgesia described in the publications investigated here differ, in some cases considerably, from the prevailing recommendations and in all studies—with the exception of rotation to methadone—they were higher than the calculated equianalgesic doses. In this light it seems advisable to ascertain whether the current guidelines, which recommend initial dose reduction on opioid rotation precisely in patients with insufficient analgesia, should be reevaluated to avoid long-term analgesic undertreatment.
From the methodological viewpoint, further high-quality RCTs with low risk of bias are required to increase the strength of evidence for the guideline recommendations, which at the moment are based largely on consensus. Overall, opioid rotation should not be withheld from properly selected patients with cancer pain, as amelioration of analgesia, reduction of side effects, and improvement in quality of life can be achieved.
Conflict of interest statement
Dr. Laufenberg-Feldmann has received lecture fees from Grünenthal.
The remaining authors declare that no conflict of interest exists.
Manuscript submitted on 11 July 2016, revised version accepted on 14 November 2017
Translated from the original German by David Roseveare
Dr. med. Michael Schuster
Klinik für Anästhesiologie, Universitätsmedizin Mainz
Langenbeckstr. 1, 55131 Mainz, Germany
For eReferences please refer to:
Dr. Schuster, PD Dr. Heid, Dr. Laufenberg-Feldmann
Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI),
University Hospital Mainz: Bayer
|1.||Bruera ED, Portenoy RK: Cancer pain. Assessment and management. 2nd edition; New York: Cambridge University Press 2010.|
|2.||Meuser T, Pietruck C, Radbruch L, Stute P, Lehmann KA, Grond S: Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology. Pain 2001; 93: 247–57 CrossRef|
|3.||Fine PG, Portenoy RK: Establishing “best practices” for opioid rotation: conclusions of an expert panel. J Pain Symptom Manage 2009; 38: 418–25 CrossRef MEDLINE PubMed Central|
|4.||Nalamachu SR: Opioid rotation in clinical practice. Adv Ther 2012; 29: 849–63 CrossRef MEDLINE|
|5.||Knotkova H, Fine PG, Portenoy RK: Opioid rotation: the science and the limitations of the equianalgesic dose table. J Pain Symptom Manage 2009; 38: 426–39 CrossRef MEDLINE|
|6.||Bohnert AS, Valenstein M, Bair MJ, et al.: Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA 2011; 305: 1315–21 CrossRef MEDLINE|
|7.||Häuser W, Bock F, Engeser P, Tölle T, Willweber-Strumpf A, Petzke F: Long-term opioid use in non-cancer pain. Dtsch Arztebl Int 2014; 111: 732–40 VOLLTEXT|
|8.||Quigley C: Opioid switching to improve pain relief and drug tolerability. Cochrane Database Syst Rev 2004; 3: CD004847 CrossRef|
|9.||Mercadante S, Caraceni A: Conversion ratios for opioid switching in the treatment of cancer pain: a systematic review. Palliat Med 2011; 25: 504–15 CrossRef MEDLINE|
|10.||Dale O, Moksnes K, Kaasa S: European palliative care research collaborative pain guidelines: opioid switching to improve analgesia or reduce side effects. A systematic review. Palliat Med 2011; 25: 494–503 CrossRef MEDLINE|
|11.||Moher D, Liberati A, Tetzlaff J, Altman DG, Group P: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6: e1000097 CrossRef MEDLINE PubMed Central|
|12.||Shea BJ, Grimshaw JM, Wells GA, et al.: Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol 2007; 7: 10 CrossRef MEDLINE PubMed Central|
|13.||Shea BJ, Hamel C, Wells GA, et al.: AMSTAR is a reliable and valid measurement tool to assess the methodological quality of systematic reviews. J Clin Epidemiol 2009; 62: 1013–20 CrossRef MEDLINE|
|14.||Higgins JPT, Altman DG, Gøtzsche PC, et al.: The cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343 CrossRef|
|15.||Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J: Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ J Surg 2003; 73: 712–6 CrossRef|
|16.||Phillips B, Ball C, Sackett D, et al.: Oxford centre for evidence-based medicine—levels of evidence, 2009. www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/ (last accessed on 31 July 2017).|
|17.||McLean S, Twomey F: Methods of rotation from another strong opioid to methadone for the management of cancer pain: a systematic review of the available evidence. J Pain Symptom Manage 2015; 50: 248–59.e1 CrossRef MEDLINE|
|18.||Imanaka K, Tominaga Y, Etropolski M, Ohashi H, Hirose K, Matsumura T: Ready conversion of patients with well-controlled, moderate to severe, chronic malignant tumor-related pain on other opioids to tapentadol extended release. Clin Drug Investig 2014; 34: 501–11 CrossRef MEDLINE PubMed Central|
|19.||Moksnes K, Dale O, Rosland JH, Paulsen O, Klepstad P, Kaasa S: How to switch from morphine or oxycodone to methadone in cancer patients? A randomised clinical phase II trial. Eur J Cancer 2011; 47: 2463–70 CrossRef MEDLINE|
|20.||Poulain P, Berleur MP, Lefki S, et al.: Efficacy and safety of two methadone titration methods for the treatment of cancer-related pain: the EQUIMETH2 trial (methadone for cancer-related pain). J Pain Symptom Manage 2016; 52: 626–36.e1 CrossRef MEDLINE|
|21.||Slatkin NE, Rhiner MI, Gould EM, Ma T, Ahdieh H: Long-term tolerability and effectiveness of oxymorphone extended release in patients with cancer. J Opioid Manag 2010; 6: 181–91 CrossRef|
|22.||Lee KH, Kim MK, Hyun MS, et al.: Clinical effectiveness and safety of OROS(R) hydromorphone in break-through cancer pain treatment: a multicenter, prospective, open-label study in Korean patients. J Opioid Manag 2012; 8: 243–52 CrossRef MEDLINE|
|23.||Lundorff L, Sjogren P, Hansen OB, Jonsson T, Nielsen PR, Christrup L: Switching from high doses of pure mu-opioid agonists to transdermal buprenorphine in patients with cancer: a feasibility study. J Opioid Manag 2013; 9: 255–62 CrossRef MEDLINE|
|24.||Mercadante S, Porzio G, Adile C, et al.: Tapentadol at medium to high doses in patients previously receiving strong opioids for the management of cancer pain. Curr Med Res Opin 2014; 30: 2063–8 CrossRef MEDLINE|
|25.||Minami S, Kijima T, Nakatani T, et al.: Opioid switch from low dose of oral oxycodone to transdermal fentanyl matrix patch for patients with stable thoracic malignancy-related pain. BMC Palliat Care 2014; 13: 46 CrossRef MEDLINE PubMed Central|
|26.||Porta-Sales J, Garzon-Rodriguez C, Villavicencio-Chavez C, Llorens-Torrome S, Gonzalez-Barboteo J: Efficacy and safety of methadone as a second-line opioid for cancer pain in an outpatient clinic: a prospective open-label study. Oncologist 2016; 21: 981–7 CrossRef MEDLINE PubMed Central|
|27.||Mercadante S, Bruera E: Opioid switching: a systematic and critical review. Cancer Treat Rev 2006; 32: 304–15 CrossRef MEDLINE|
|28.||Baxter LES, Campbell A, DeShields M, et al.: Safe methadone induction and stabilization: report of an expert panel. J Addict Med 2013; 7: 377–86 CrossRef MEDLINE|
|29.||Gagnon B, Bruera E: Differences in the ratios of morphine to methadone in patients with neuropathic pain versus non-neuropathic pain. J Pain Symptom Manage 1999; 18: 120–5 CrossRef|
|30.||Ostgathe C, Voltz R, van Aaaken A, et al.: Practicability, safety, and efficacy of a “German model” for opioid conversion to oral levo-methadone. Support Care Cancer 2011; 20: 2105–10 CrossRef MEDLINE|
|31.||Ripamonti C, Groff L, Brunelli C, Polastri D, Stavrakis A, De Conno F: Switching from morphine to oral methadone in treating cancer pain: what is the equianalgesic dose ratio? J Clin Oncol 1998; 16: 3216–21 CrossRef MEDLINE|
|32.||Ayonrinde OT, Bridge DT: The rediscovery of methadone for cancer pain management. Med J Aust 2000; 173: 536–40 MEDLINE|
|33.||Mercadante S: Switching methadone: a 10-year experience of 345 patients in an acute palliative care unit. Pain Med 2012; 13: 399–404 CrossRef MEDLINE|
|34.||Friedman L: Pain management in palliative care. Clinics in Family Practice 2004; 6: 371–93 CrossRef|
|35.||Morley J, Makin M: The use of methadone in cancer pain poorly responsive to other opioids. Pain Rev 1998; 5: 51–8 CrossRef|
|36.||Hagen NA, Wasylenko E: Methadone: outpatient titration and monitoring strategies in cancer patients. J Pain Symptom Manage 1999; 18: 369–75 CrossRef|
|37.||Laugsand EA, Jakobsen G, Kaasa S, Klepstad P: Inadequate symptom control in advanced cancer patients across Europe. Support Care Cancer 2011; 19: 2005–14 CrossRef MEDLINE PubMed Central|
|38.||Holzer P, Ahmedzai SH, Niederle N, et al.: Opioid-induced bowel dysfunction in cancer-related pain: causes, consequences, and a novel approach for its management. J Opioid Manag 2009; 5: 145–51 CrossRef MEDLINE|
|39.||Lange B, Kuperwasser B, Okamoto A, et al.: Efficacy and safety of tapentadol prolonged release for chronic osteoarthritis pain and low back pain. Adv Ther 2010; 27: 381–99 CrossRef CrossRef MEDLINE|
|40.||Wild JE, Grond S, Kuperwasser B, et al.: Long-term safety and tolerability of tapentadol extended release for the management of chronic low back pain or osteoarthritis pain. Pain Pract 2010; 10: 416–27 CrossRef MEDLINE|
|e1.||Caraceni A, Hanks G, Kaasa S, et al.: Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. Lancet Oncol 2012; 13: e58-68 CrossRef MEDLINE|
|e2.||Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): Palliativmedizin für Patienten mit einer nicht heilbaren Krebserkrankung, Langversion 1.1, 2015, AWMF-Registernummer: 128/001OL. www.leitlinienprogramm-onkologie.de/index.php?id=80&type=0 (last accessed on 31 July 2017).|
|e3.||National Health Service Scotland—NHS: Scottish palliative care guidelines: choosing and changing opioids 2014. www.palliativecareguidelines.scot.nhs.uk/media/1215/scottish-palliative-care-guidelines-choosing-and-changing-opioids.pdf (last accessed on 31 July 2017).|
|e4.||National Institute for Health and Care Excellence – NICE: Clinical guideline [CG140] palliative care for adults: strong opioids for pain relief 2016. www.nice.org.uk/guidance/cg140 (last accessed on 31 July 2017).|
|e5.||National Comprehensive Cancer Network (NCCN): Clinical practice guidelines in oncology: adult pain (Version 2.2016). www.oralcancerfoundation.org/wp-content/uploads/2016/09/pain.pdf (last accessed on 31 July 2017).|
|e6.||Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) - Ständige Kommission Leitlinien: AWMF-Regelwerk „Leitlinien“, 1st edition 2012. www.awmf.org/leitlinien/awmf-regelwerk.html (last accessed on 31 July 2017).|
|e7.||Roxane Laboratories: Produktinformation—dolophine hydrochloride 2006. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM142842.pdf (last accessed on 31 July 2017).|
|e8.||Afsharimani B, Kindl K, Good P, Hardy J: Pharmacological options for the management of refractory cancer pain-what is the evidence? Support Care Cancer 2015; 23: 1473–81 CrossRef MEDLINE|
|e9.||Agbalaka A, Schwenke K, Litzenburger B: Tapentadol prolonged release for the treatment of severe chronic tumor pain in routine clinical practice. MMW Fortschr Med 2012; 154 (Suppl 4): 123–30 MEDLINE|
|e10.||Argoff C, Arnstein P, Stanos S, et al.: Relationship between change in pain intensity and functional outcomes in patients with chronic pain receiving twice daily extended-release hydrocodone bitartrate. J Opioid Manag 2015; 11: 417–24 CrossRef MEDLINE|
|e11.||Baron R, Eberhart L, Kern KU, et al.: Tapentadol prolonged release for chronic pain: a review of clinical trials and 5 years of routine clinical practice data. Pain Pract 2017; 17: 678–700 CrossRef MEDLINE|
|e12.||Berland DW, Malinoff HL, Weiner MA, Przybylski R: When opioids fail in chronic pain management: the role for buprenorphine and hospitalization. Am J Ther 2013; 20: 316–21 CrossRef MEDLINE|
|e13.||Bradley AM, Valgus JM, Bernard S: Converting to transdermal fentanyl: avoidance of underdosing. J Palliat Med 2013; 16: 409–11 CrossRef MEDLINE|
|e14.||Broglio K, Pergolizzi J, Kowalski M, Lynch SY, He E, Wen W: Efficacy and safety of once-daily extended-release (ER) hydrocodone in individuals previously receiving ER morphine for chronic pain. Pain Pract 2017; 17: 382–91 CrossRef MEDLINE|
|e15.||Bruera E, Paice JA: Cancer pain management: safe and effective use of opioids. Am Soc Clin Oncol Educ Book 2015: e593–9 MEDLINE|
|e16.||Coluzzi F, Mattia C: OROS(R) hydromorphone in chronic pain management: when drug delivery technology matches clinical needs. Minerva Anestesiol 2010; 76: 1072–84 MEDLINE|
|e17.||Gatti A, Reale C, Luzi M, et al.: Effects of opioid rotation in chronic pain patients: ORTIBARN study. Clin Drug Investig 2010; 30 (Suppl 2): 39–47.|
|e18.||Gonzalez-Barboteo J, Trelis-Navarro J, Tuca-Rodriguez A, Gomez-Batiste X: Opioid rotation: a therapeutic choice in the management of refractory cancer pain. Med Clin (Barc) 2010; 135: 617–22.|
|e19.||Gonzalez-Barboteo J, Alentorn XG, Manuel FA, et al.: Effectiveness of opioid rotation in the control of cancer pain: the ROTODOL study. J Opioid Manag 2014; 10: 395–403 CrossRef MEDLINE|
|e20.||Hanaoka K, Yoshimura T, Tomioka T, Sakata H: Clinical study of one-day fentanyl patch in patients with cancer pain—evaluation of the efficacy and safety in relation to treatment switch from opioid analgesic therapy. Masui 2011; 60: 147–56 MEDLINE|
|e21.||Ikeda M, Sonoo H, Kurebayashi J, et al.: A pilot study of the reduced effects of adverse events caused by oral morphine and oxycodone after rotating to fentanyl patch in patients with metastatic breast cancer. Gan To Kagaku Ryoho 2012; 39: 599–603.|
|e22.||Kanbayashi Y, Hosokawa T, Okamoto K, et al.: Factors predicting requirement of high-dose transdermal fentanyl in opioid switching from oral morphine or oxycodone in patients with cancer pain. Clin J Pain 2011; 27: 664–7 CrossRef MEDLINE|
|e23.||Kern KU, Krings D, Waldmann-Rex S: Tapentadol prolonged release improves analgesia, functional impairment and quality of life in patients with chronic pain who have previously received oxycodone/naloxone. MMW Fortschr Med 2014; 156 (Suppl 2): 54–63.|
|e24.||Khojasteh A, Evans W, Reynolds R, Thomas G, Savarese J: Controlled-release oral morphine sulfate in the treatment of cancer pain with pharmacokinetic correlation. J Clin Oncol 2012; 5: 956–61.|
|e25.||Kim HJ, Kim YS, Park SH: Opioid rotation versus combination for cancer patients with chronic uncontrolled pain: a randomized study. BMC Palliat Care 2015; 14: 41 CrossRef MEDLINE PubMed Central|
|e26.||Lawlor P, Chan R, Tucker T, Creedon B, Bennett K, Pereira J: A pilot phase report of a randomized trial comparing two strategies for switching to methadone in cancer pain (CP) management. Support Care Cancer 2012; 20: 196.|
|e27.||Leppert W: Role of oxycodone and oxycodone/naloxone in cancer pain management. Pharmacol Rep 2010; 62: 578–91 CrossRef|
|e28.||McNamara P: Opioid switching from morphine to transdermal fentanyl for toxicity reduction in palliative care. Palliat Med 2012; 16: 425–34.|
|e29.||Mercadante S: Cancer pain. Curr Opin Support Palliat Care 2013; 7: 139–43 CrossRef MEDLINE|
|e30.||Mercadante S, Porzio G, Aielli F, et al.: Opioid switching from and to tapentadol extended release in cancer patients: conversion ratio with other opioids. Curr Med Res Opin 2013; 29: 661–6 CrossRef MEDLINE|
|e31.||Mercadante S, Ferrera P, Villari P, Adile C, Casuccio A: Switching from oxycodone to methadone in advanced cancer patients. Support Care Cancer 2012; 20: 191–4 CrossRef MEDLINE|
|e32.||Mücke M, Conrad R, Marinova M, et al.: Dose-finding for treatment with a transdermal fentanyl patch: titration with oral transmucosal fentanyl citrate and morphine sulfate. Schmerz 2016; 30: 560–7 CrossRef MEDLINE|
|e33.||Ravera E, di Santo S, Bosco R, Arboscello C, Chiarlone R: Controlled-release oxycodone tablets after transdermal-based opioid therapy in patients with cancer and non-cancer pain. Aging Clin Exp Res 2011; 23: 328–32 CrossRef|
|e34.||Rhondali W, Tremellat F, Ledoux M, Ciais JF, Bruera E, Filbet M: Methadone rotation for cancer patients with refractory pain in a palliative care unit: an observational study. J Palliat Med 2013; 16: 1382–7 CrossRef MEDLINE|
|e35.||Riley J, Branford R, Droney J, et al.: Morphine or oxycodone for cancer-related pain? A randomized, open-label, controlled trial. J Pain Symptom Manage 2015; 49: 161–72 CrossRef MEDLINE|
|e36.||Roberto A, Galli F, Floriani I, Corli O: Are strong opioids equally effective and safe in the treatment of chronic cancer pain? Results from CERP study. Palliative Medicine Conference: 9th world research congress of the european association for palliative care, EAPC 2016 Ireland: Np34-np5.|
|e37.||Roland CL, Setnik B, Cleveland JM, Brown DA: Clinical outcomes during opioid titration following initiation with or conversion to Remoxy(R), an extended-release formulation of oxycodone. Postgrad Med 2011; 123: 148–59 CrossRef MEDLINE|
|e38.||Schwittay A, Schumann C, Litzenburger BC, Schwenke K: Tapentadol prolonged release for severe chronic pain. Results of a non-interventional study involving general practitioners and internists. MMW Fortschr Med 2012; 154 (Suppl 3): 85–93.|
|e39.||Schwittay A, Schumann C, Litzenburger BC, Schwenke K: Tapentadol prolonged release for severe chronic pain: results of a noninterventional study involving general practitioners and internists. J Pain Palliat Care Pharmacother 2013; 27: 225–34 CrossRef MEDLINE|
|e40.||Sittl R: Transdermal buprenorphine in cancer pain and palliative care. Palliat Med 2017; 20: 25–30.|
|e41.||Trescot AM: Review of the role of opioids in cancer pain. J Natl Compr Canc Netw 2010; 8: 1087–94 CrossRef|
|e42.||Vissers KC, Besse K, Hans G, Devulder J, Morlion B: Opioid rotation in the management of chronic pain: where is the evidence? Pain Pract 2010; 10: 85–93 CrossRef MEDLINE|
|e43.||Wahle K, Krings D, Schwenke K: Pain therapy in the elderly: 7-day transdermal buprenorphine patch in clinical practice. Results of a non-interventional study. MMW Fortschr Med 2013; 155 (Suppl 1): 25–31.|
|e44.||Wallace M, Rauck R, Moulin D, Thipphawong J, Khanna S, Tudor I: Conversion from standard opioid therapy to once-daily oral extended-release hydromorphone in patients with chronic cancer pain. J Int Med Res 2012; 36: 343–52.|
|e45.||Webster LR, Brewer R, Morris D, Cleveland JM, Setnik B: Opioid titration and conversion in patients receiving morphine sulfate and naltrexone hydrochloride extended release capsules. Postgrad Med 2011; 123: 155–64 CrossRef MEDLINE|
|e46.||Webster L, Gruener D, Kirby T, Xiang Q, Tzanis E, Finn A: Evaluation of the tolerability of switching patients on chronic full μ-opioid agonist therapy to buccal buprenorphine. Pain Med 2016; 17: 899–907 PubMed Central|