Treatment Of Pain In Cancer Patients Research Articles

Bone Pain in Cancer Patients: Mechanisms and Current Treatment.

The skeletal system is the third most common site for cancer metastases, surpassed only by the lungs and liver. Many tumors, especially those of the breast, prostate, lungs, and kidneys, have a strong predilection to metastasize to bone, which causes pain, hypercalcemia, pathological skeletal fractures, compression of the spinal cord or other nervous structures, decreased mobility, and increased mortality. Metastatic cancer-induced bone pain (CIBP) is a type of chronic pain with unique and complex pathophysiology characterized by nociceptive and neuropathic components. Its treatment should be multimodal (pharmacological and non-pharmacological), including causal anticancer and symptomatic analgesic treatment to improve quality of life (QoL). The aim of this paper is to discuss the mechanisms involved in the occurrence and persistence of cancer-associated bone pain and to review the treatment methods recommended by experts in clinical practice. The final part of the paper reviews experimental therapeutic methods that are currently being studied and that may improve the efficacy of bone pain treatment in cancer patients in the future.

Pharmacotherapy of pain in cancer patients – recommendations of the Polish Association for the Study of Pain, Polish Society of Palliative Medicine, Polish Society of Oncology, Polish Society of Family Medicine, and Polish Society of Anaesthesiology and Intensive Therapy

for the pharmacotherapy of pain in cancer patients were developed by a group of 21 experts of the Polish Association for the Study of Pain, Polish Society of Palliative Medicine, Polish Society of Oncology, Polish Society of Family Medicine, and Polish Society of Anaesthesiology and Intensive Therapy. During a series of meetings, the experts carried out an overview of the available literature on the treatment of pain in cancer patients, paying particular attention to systematic reviews and more recent randomized studies not included in the reviews. The search was performed in the EMBASE, MEDLINE, and Cochrane Central Register of Controlled Trials databases using such keywords as “pain”, “cancer”, “pharmacotherapy”, “analgesics”, and similar. The overviewed articles included studies of pathomechanisms of pain in cancer patients, methods for the assessment of pain in cancer patients, and drugs used in the pharmacotherapy of pain in cancer patients, including non-opioid analgesics (paracetamol, metamizole, non-steroidal anti-inflammatory drugs), opioids (strong and weak), coanalgesics (glucocorticosteroids, α2-adrenergic receptor agonists, NMDA receptor antagonists, antidepressants, anticonvulsants, topical medications) as well as drugs used to reduce the adverse effects of the analgesic treatment and symptoms other than pain in patients subjected to opioid treatment. The principles of opioid rotation and the management of patients with opioidophobia were discussed and recommendations for the management of opioid-induced hyperalgesia were presented. Drugs used in different types of pain experienced by cancer patients, including neuropathic pain, visceral pain, bone pain, and breakthrough pain, were included in the overview. Most common interactions of drugs used in the pharmacotherapy of pain in cancer patients as well as the principles for the pharmacotherapy of pain in cancer patients with organ dysfunctions (circulatory failure, chronic obstructive pulmonary disease, renal or hepatic failure) were also discussed. In addition, principles for the management of crisis situations as well as cases of opioid overdose or opioid-induced respiratory depression were presented. In the final part of the recommendations, the issues of pain and care in dying patients are discussed. Recommendations are addressed to physicians of different specialties involved in the diagnostics and treatment of cancer in their daily practice. It is the hope of the experts who took part in the development of these recommendations that the recommendations would become helpful in everyday medical practice and thus contribute to the improvement in the quality of care and the efficacy of pain treatment in this group of patients.

Nurses’ role in the non-pharmacological pain treatment in cancer patients

ABSTRACT BACKGROUND AND OBJECTIVES: Non-pharmacological therapy is important and complements the pharmacological treatment to relieve the pain and anxiety in many patients, and it is also classified as complementary and integrative therapy. The objective of this study was to describe the nurses’ role in non-pharmacological pain management in cancer patients. CONTENTS: Integrative literature review. Scientific publications indexed in the Medline, Integrated Building Environmental Communications System, LILACS and Nursing databases, accessed through the Virtual Health Library in October 2016, were evaluated. Following the inclusion criteria, seven studies were selected, published between 2006 and 2016. Data were subjected to content analysis. Based on this analysis, the articles were described in three categories: 1) the perception of nurses; 2) the perception of the patient, and 3) nursing actions. CONCLUSION: It was evident the fundamental and important role of the nursing staff in the non-pharmacological pain management in cancer patients. Both patients and family members should actively participate in the treatment. It is recommended the development of reliable and effective communication links, in addition to the implementation of educational actions involving the triad patient-family-team.

Clinically significant drug-drug interactions involving opioid analgesics used for pain treatment in patients with cancer: a systematic review.

BackgroundOpioids are the most frequently used drugs to treat pain in cancer patients. In some patients, however, opioids can cause adverse effects and drug–drug interactions. No advice concerning the combination of opioids and other drugs is given in the current European guidelines.ObjectiveTo identify studies that report clinically significant drug–drug interactions involving opioids used for pain treatment in adult cancer patients.Design and data sourcesSystematic review with searches in Embase, MEDLINE, and Cochrane Central Register of Controlled Trials from the start of the databases (Embase from 1980) through January 2014. In addition, reference lists of relevant full-text papers were hand-searched.ResultsOf 901 retrieved papers, 112 were considered as potentially eligible. After full-text reading, 17 were included in the final analysis, together with 15 papers identified through hand-searching of reference lists. All of the 32 included publications were case reports or case series. Clinical manifestations of drug–drug interactions involving opioids were grouped as follows: 1) sedation and respiratory depression, 2) other central nervous system symptoms, 3) impairment of pain control and/or opioid withdrawal, and 4) other symptoms. The most common mechanisms eliciting drug–drug interactions were alteration of opioid metabolism by inhibiting the activity of cytochrome P450 3A4 and pharmacodynamic interactions due to the combined effect on opioid, dopaminergic, cholinergic, and serotonergic activity in the central nervous system.ConclusionEvidence for drug–drug interactions associated with opioids used for pain treatment in cancer patients is very limited. Still, the cases identified in this systematic review give some important suggestions for clinical practice. Physicians prescribing opioids should recognize the risk of drug–drug interactions and if possible avoid polypharmacy.

Tramadol plus metamizole combined or not with anti-inflammatory drugs is clinically effective for moderate to severe chronic pain treatment in cancer patients

ObjectiveTo test the effectiveness and safety of tramadol plus metamizole combined or not with a non-steroidal anti-inflammatory drug (NSAID) for treating moderate to severe chronic neoplastic pain in dogs, and its impact on quality of life (QL). Study designProspective, uncontrolled, open-label, clinical study. AnimalsSixty nine client-owned dogs with multiple forms of cancer and visual analog scale (VAS) pain score ≥40 after receiving NSAIDs for at least 7 days. MethodsThe MN group received metamizole + NSAID, MNT group received metamizole + NSAID + tramadol and MT group received metamizole + tramadol. Pain was scored by the 0 to 100 mm VAS (0 = no pain, 100 = worst pain) and analgesic therapy was considered effective if 25 mm differences in VAS scores were observed between day 0 and the follow ups. The QL was evaluated according to a 0 to 36 scoring method for dogs (0 = worst, 36 = best) and side effects were recorded. Data were registered at day 0 (baseline) and at the first and second follow ups (7 and 14 days after day 0, respectively). ResultsThe MN group had less analgesia at day 7 (25%) and day 14 (42%) than MNT (59%, p = 0.0274; 76%, p = 0.0251, respectively) and MT groups (69%, p = 0.0151; 81%, p = 0.0341, respectively). The QL scores were lower in the MN group at the first (score 23) and second follow up (score 26) than in MNT (27, p = 0.0847; 30, p = 0.0002) and MT (28, p = 0.0384; 31, p = 0.0001) groups. Side effects were more commonly observed in the MN group (87%) than in MNT (24%, p < 0.0001) and MT groups (25%, p = 0.0003) at the first follow up. Conclusions and clinical relevanceTramadol plus metamizole combined or not with NSAID were well tolerated and clinically effective to treat moderate to severe pain in dogs with cancer and improved QL.

がん性疼痛に対する持続くも膜下オピオイド鎮痛法に伴う神経病理学的所見

くも膜下オピオイド鎮痛法 (ITO)に伴う脊髄神経細胞の変性壊死や脱髄などの脊髄, 神経障害に関して病理組織学的に研究された報告はきわめて少ない. ITOにより神経組織障害が引き起こされたとする報告とないとする報告があり, 意見の一致をみていない. 今回ITOを施行された7症例 (男性4名, 女性3名)の剖検材料を用いて神経病理学的に検討した. モルヒネとブピバカインの投与が6例, フェンタニルとブピバカインの投与が1例であり投与期間は6～345日である. モルヒネを長期間投与した2症例は高度の脊髄神経細胞の変性壊死, グリオーシスおよび後角, 後根の脱髄が認められたが, 短期間しか投与しなかった4症例およびフェンタニル投与例ではこれらの神経病理学的変化は認められなかった. ITOで使用したモルヒネの総投与量および投与期間と脊髄神経障害の程度には関連性があり, ITOによる神経障害には主としてモルヒネが関与していると考えられた.

Oral trasmucosal fentanyl citrate for breakthrough pain treatment in cancer patients

Introduction: Breakthrough cancer pain has been defined as a transitory increase in pain intensity that occurs either spontaneously or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain. The availability of supplemental doses of oral opioids, in addition to the continuous analgesic medication, is the main treatment suggested to manage pain flares.Areas covered: Oral transmucosal fentanyl citrate (OTFC) is the first product of a new generation of delivery systems, named rapid-onset opioids (ROOs), characterized by rapidity of effect and the short duration of analgesia. Controlled studies and long-term experience have shown that OTFC is an effective treatment for breakthrough pain management and its use should be considered in any patient experiencing breakthrough pain related to cancer.Expert opinion: The onset of action of OTFC – demonstrated to start within 15 min – and the short time to maximum concentration make it a useful indication for breakthrough pain; dose titration is commonly recommended. However, it is likely that patients receiving high doses of opioids for background analgesia will not be candidates for titration with minimal initial doses of OTFC, as they are opioid tolerant and the process would be time consuming.

Pain in cancer. An outcome research project to evaluate the epidemiology, the quality and the effects of pain treatment in cancer patients.

BackgroundManagement of pain related to advanced or metastatic cancer, although the availability of several pharmacological and non-pharmacological interventions and the existence of well-known guidelines and protocols, is often difficult and inadequate. Evidence of the relative effectiveness of current options for treating cancer pain from comparative randomized studies is scanty.MethodsIn the context of a wider project, a multicenter, open label, prospective Outcome Research study will be launched in Italy in 2006 to investigate the epidemiology of cancer pain and of its treatments, the quality of analgesic-drug therapy and the effectiveness of alternative analgesic strategies in a large, prospective, unselected cohort of cancer patients using the state-of-the art of patient-reported-outcomes. About 100 Italian centers will recruit 2500 patients with advanced/progressive/metastatic cancer with pain (related to the cancer disease) requiring analgesic treatments. Each center is expected to recruit 25 consecutive and eligible patients during the study inception period. Approximately two months will be allowed for subject recruitment and enrollment. Subject evaluation and follow-up will be for 3 months. The effect on outcomes of various therapeutic analgesic options administered by physicians, given the observational approach where patients are not assigned at random to different treatments, will be compared using the propensity score approach, allowing the adjustment for treatment selection bias. Later, after the launch of the observational study and on the basis of results, in specific subsamples of patients and in select centers of the network, a Randomized Controlled Trial will be carried out to formally compare the efficacy of alternative analgesic strategies, with particular emphasis on oral morphine (as comparator) and buprenorphine patch (as experimental arm). Results from the outcome (cohort) and experimental (Randomized Controlled Trial) studies will ensure both the external and internal validity.

Improving the quality of pain treatment by a tailored pain education programme for cancer patients in chronic pain

Educational interventions, aiming to increase patients' knowledge and attitude regarding pain, can affect pain treatment. The purpose of this study was to evaluate the effects of a Pain Education Programme (PEP), on adequacy of pain treatment, and to describe characteristics predicting change in adequacy. The PEP consists of a multi-method approach in which patients are educated about the basic principles regarding pain, instructed how to report pain in a pain diary, how to communicate about pain, and how to contact healthcare providers. The effects of the PEP were evaluated taking into consideration the lack of well-established outcome measures to evaluate adequacy of pain treatment, the lack of long-term follow-up, and the influence of missing data.A prospective, randomized study was utilized in which 313 chronic cancer patients were followed-up until 8 weeks postdischarge. Adequacy of pain treatment was evaluated by means of the Amsterdam Pain Management Index (APMI), consisting of an integrated score of patients' Present Pain Intensity, Average Pain Intensity, and Worst Pain Intensity, corrected for patients' Tolerable Present Pain, with the analgesics used by the patient.At pretest, 60% of the patients in the hospital were treated inadequately for their pain. Postdischarge, the control group patients were significantly more inadequately treated at 2 weeks after discharge (56%vs 41%), at 4 weeks after discharge (62%vs 42%) and at 8 weeks after discharge (57%vs 51%) than the intervention group patients. While the level of inadequacy in the control groups remained relatively stable at all assessment points, a slight increase in the percentage of patients being treated inadequately was found in the intervention group patients over time. A beneficial effect of the PEP was found for patients both with and without district nursing. Variables predicting an improvement in adequacy of pain treatment consisted of the PEP, the APMI score at baseline, patients' level of physical functioning, patients' level of social functioning, the extent of adherence to pain medication, patients' pain knowledge, and the amount of analgesics used.These findings suggest that quality of pain treatment in cancer patients with chronic pain can be enhanced by educating patients about pain and improving active participation in their own pain treatment. The benefit from the PEP, however, decreases slightly over time, pointing at a need for ongoing education.

The Amsterdam Pain Management Index compared to eight frequently used outcome measures to evaluate the adequacy of pain treatment in cancer patients with chronic pain

There is no ‘gold standard’ to assess the adequacy of pain treatment in cancer patients. The purpose of the study is to explore the Amsterdam Pain Management Index, a newly designed measure to evaluate the adequacy of cancer pain treatment, and to compare it with eight frequently used outcome measures. The Amsterdam Pain Management Index compares patients’ Present Pain Intensity, Average Pain Intensity, and Worst Pain Intensity with a composite score of analgesics used, while correcting for what a patient considers as a tolerable level of pain. The eight frequently used outcome measure consisted of three Pain Intensity Markers, the Pain Relief Scale, the Patient Satisfaction Scale, and three Pain Management Indexes. In a randomized controlled trial, 313 cancer patients with a pain duration of at least 1 month were included and followed-up three times until 2 months postdischarge at home. The experimental group received a Pain Education Program, consisting of tailored pain information and instruction. Results showed that, except for the three Pain Management Indexes, the agreement between the measures was very low to moderate. The test of known-groups comparisons and equivalence between groups indicated that the Amsterdam Pain Management Index showed promising results. The Pain Intensity Markers and the Pain Relief Scale were limited in discriminating between groups, while the Patient Satisfaction Scale showed no differences between patient groups. Although it was possible for the Pain Management Indexes to distinguish between patient groups, the differences were not in the expected direction. The ability of the outcome measures to detect changes over time was clearly demonstrated by all outcome measures. Effects of the intervention were only found for the Amsterdam Pain Management Index and patients’ Substantial Worst Pain score. Although support was provided for the use of the Amsterdam Pain Management Index, more research is warranted.

Quality of life in cancer patients

Cancer and cancer therapies, including chemotherapy, radiotherapy, and surgery, all have a significant impact on the quality of life (QOL) of a patient. Poor QOL can jeopardize completion of the cancer treatment regimen since it may influence the patient's willingness to continue with cancer therapy. Whether treatment is intended as palliative or curative, it is important to design treatments where there is an acceptable tradeoff between probability of cure and QOL, or between survival time and QOL. These considerations are becoming increasingly important since newer potent therapeutic therapies have not only improved cure rates for many types of cancer, but have also greatly prolonged survival times for incurable cancers. For these reasons, QOL measurements have become increasingly important when determining efficacy of treatments in clinical trials. This conference was organized to review and discuss the issues relating to QOL in cancer patients. There can be a variety of causes of QOL deficits in cancer patients, including pain, depression, anaemia, and fatigue. The increased use of adjuvant chemotherapy and radiotherapy and their associated side effects (i.e. nausea and vomiting) have caused increased concern regarding QOL. Moreover, the longer survival times of patients with incurable cancers have increased the need to improve the palliative care they receive. The establishment of standardized QOL assessment tools will facilitate the use of QOL as an efficacy measure. In addition, the increased use of QOL measures addresses the growing awareness that it is important to treat the whole patient, not just the disease. The need for accurate instruments to measure QOL had led to the development of the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire and the Functional Assessment of Chronic Illness Therapy (FACIT) QOL measurement system. The conference, entitled 'Quality of Life in Cancer Patients', included a thorough discussion of the factors that need to be considered for proper implementation of the QOL questionnaires and interpretation of the data. These factors included language issues, cross-cultural sensitivity of the questionnaire, and the degree of disease severity. Methods on assuring validity and reliability of the questionnaire were also discussed. The discussion then moved on to potential barriers to effective utilization of QOL assessments. Despite the advances made in QOL instrument development, many clinicians are not comfortable with the use of these tools. Fundamental misunderstandings regarding the use of these instruments include improper administration, analysis and interpretation of the data. Appropriate strategies to overcome these barriers were then discussed. The conference also included an overview of the recent progress in improving QOL in cancer patients. Areas such as depression, pain, fatigue and nausea were discussed. Special attention was paid to anaemia and fatigue as well as pain. Fatigue is a common symptom of cancer patients and is quite often the result of anaemia. Several large studies assessing the QOL benefits of epoetin alfa treatment in anaemic cancer patients were reviewed. Despite the development of guidelines for pain treatment in cancer patients, pain is still undertreated in an alarmingly high percentage of patients. Barriers to effective pain management were reviewed with a discussion on ways to overcome them. In summary, the following articles will highlight the importance of QOL assessment in both clinical trials and practice when treating cancer patients. It will also provide helpful information on the development and use of questionnaires, as well as methods to analyse and achieve proper interpretation of the collected QOL data. Clinicians may also find useful information on overcoming the obstacles to effective use of QOL assessment in clinical practice, particularly for the management of anaemia and pain.

Attitudes of Italian general practitioners in the treatment of cancer pain. The Committee of the Associazione Italiana di Oncologia Medica (AIOM).

The attitude of Italian general practitioners in prescribing practices for patients with cancer pain was assessed by means of a questionnaire. The results indicated that among most of the doctors who completed the questionnaire the basic principles of pain treatment in cancer patients are largely understood. Oral morphine emerged as the most commonly used opioid (60%) and controlled-release morphine as the preferred preparation. Non-steroidal anti-inflammatory drugs were the most commonly used minor analgesics. Fear of side effects and restrictive prescribing regulations emerged as the most important barrier against adequate pain management. The survey emphasised the need for continued efforts in implementing specific educational programming for improvement in cancer pain management.

Neuropathologic Findings after Long-term Intrathecal Infusion of Morphine and Bupivacaine for Pain Treatment in Cancer Patients

Epidural or intrathecal infusions of morphine and bupivacaine mixtures are presently used for the treatment of "refractory" cancer pain even though the neurotoxic potential of such mixtures is unknown. The pathologic findings of the spinal column, the meninges, the nerve roots, and the spinal cord, and the clinical neurologic deficits were recorded in 15 patients (5 men and 10 women), aged 26-83 (median 68) yr, treated for 4-274 (median 81) days with intrathecal infusions of morphine (with preservatives [sodium metabisulfite and sodium edetate]) and bupivacaine mixtures, given through open, subcutaneously tunneled nylon catheters. Six patients had been subjected to radiation therapy (20-96 Gy), applied over the spinal column, and four had been treated with antineoplastics believed to be neurotoxic. Ten patients had various neurologic deficits before the intrathecal treatment. The cumulative doses (ranges) given intrathecally were: morphine 33-11,900 mg, sodium metabisulfite 3.3-1,050 mg, sodium edetate 0.33-105 mg, and bupivacaine 10-41,400 mg; cumulative volumes were 16-9,400 ml. The concentrations of the drugs in the mixtures were: morphine 0.25-4.0 mg/ml, sodium metabisulfite 0.025-0.40 mg/ml, sodium edetate 0.0025-0.04 mg/ml, and bupivacaine 3.0-4.75 mg/ml. The osmolality of the mixtures in vitro ranged from 282 to 286 mOsm/kg and the pH from 4.1 to 4.6. The pathologic findings consisted of vertebral metastases (n = 6), epidural and/or intrathecal tumor masses (n = 8), focal subdural fibrosis (n = 6), infiltration of mononuclear cells in the subarachnoid space (n = 10), and discrete injuries (nerve fiber degeneration or fibrosis) to the anterior (five patients) and posterior (seven) nerve roots, and spinal cord (tumor compression [one], slight thickening of the leptomeninges [one], and thrombosis of a spinal artery and medullary infarction [one]). In none of the cases was any reaction against the nylon catheter within its subarachnoid course recorded. The neuropathologic findings were not related to the duration or cumulative doses of the intrathecal treatment. No new neurologic deficits that could be attributed to the intrathecal administration of the opiate-bupivacaine mixtures were recorded. The neuropathologic and clinical neurologic findings in cancer patients treated with intrathecal morphine-bupivacaine mixtures appeared similar to those in animals and humans reported with either intrathecal morphine or bupivacaine alone.

Pain causes in 200 patients referred to a multidisciplinary cancer pain clinic

Causes of pain were analysed in 200 patients referred to a specialized cancer pain clinic. Pain caused by tumour growth was found in 158 patients, pain secondary to cancer or its treatment in 116 patients and pain unrelated to cancer in 33 patients. Visceral involvement (74 cases), bone metastases (68 cases), soft tissue invasion (56 cases) and nerve/plexus pressure or infiltration (39 cases) were the most frequent causes of pain due to tumour growth. Myogenic pain (68 cases) was the most frequent cause of secondary pain. The patients presented with a multitude of different combinations of causes of pain, the majority having at least two separate causes. Since pain treatment in cancer patients should be determined by its aetiology, a detailed analysis of the pain condition in each patient should form the basis for a rational therapy.

Trial of Intravenous Lidocaine on Painful Neuropathy in Cancer Patients

In 10 cancer patients with cutaneous allodynia, intravenous lidocaine (5 mg/kg body weight) or 0.9% NaCl was given in a double blind, cross-over study to determine the analgesic effect. One patient had complete and one had partial pain relief with lidocaine infusion, whereas three patients experienced partial pain relief with placebo. Neither lidocaine nor placebo reduced pain intensity or consumption of analgesics significantly during the study period. Intravenous infusion of lidocaine cannot be recommended as routine pain treatment in cancer patients with cutaneous allodynia or pain, but further studies are needed to test the effect of lidocaine on different peripheral stimuli.

Ethical and Clinical Aspects of Pain Treatment in Cancer Patients

Ethical and Clinical Aspects of Pain Treatment in Cancer Patients