Adherence to Analgesics in Oncology Outpatients: Focus on Taking Analgesics on Time.

BACKGROUND: Inadequate adherence to prescribed analgesics may be one of the reasons why patients with cancer experience unrelieved pain. Adherence is directly influenced by patients' barriers about pain management. Patient pain education programs (PEPs) have been developed to reduce patients' barriers and increase patients' adherence to their analgesics. The purpose of this article was to evaluate patients' adherence in patients receiving a pain consult and patient pain education in comparison with patients receiving standard pain treatment (standard care [SC]), to better explore the difficulties in medication adherence in cancer-related pain and the effects of PEP. METHODS: In 54 adult outpatients with cancer-related pain, patients' adherence to the prescribed around-the-clock analgesics was measured with a Medication Event Monitoring System, in the following time intervals: weeks 1 and 2, weeks 3 and 4, and weeks 7 and 8 after randomization. Adherence was differentiated into taking adherence, taking the correct dose, and taking analgesics at the right time intervals. RESULTS: Taking adherence increased in the intervention group compared to baseline (from 91% to 93%) and decreased in the SC group (from 85% to 78%; P < 0.05). At the end of the study, more patients in the intervention group took their analgesics at the right intervals (78%) than did patients in the SC group (64%, P < 0.05). During the study, patients were more adherent to opioids than to World Health Organization step 1 analgesics. CONCLUSION: The combined intervention can increase adherence. The true problem in pain management is that patients do not take their prescribed analgesics at the right time intervals. With the detailed adherence information from this study, it is possible to further tailor patient education to the individual patient.

Can you help me feel less exhausted all the time?

A 64-year-old woman with metastatic rectal cancer is admitted to the acute palliative care unit of our cancer center because of debilitating fatigue. She had been diagnosed with metastatic disease in 2009, when liver metastases were found 1 year after the primary treatment of her rectal cancer with preoperative radiotherapy and low anterior resection. Since then, she had been treated with resection of liver metastases in 2009 and 2010, palliative combination chemotherapy (oxaliplatin plus capecitabine) after the diagnosis of new liver and lung metastases in 2010, irinotecan in 2011, and then cetuximab until progression. She declined participation in a phase I clinical trial because she was afraid of experiencing adverse effects; she felt relatively well at the time. She had functioned without hindering symptoms until 2 weeks before admission. Her condition had deteriorated markedly since then. At admission, she is bedridden because of progressive fatigue. Furthermore, she complains of dyspnea and nausea and vomits approximately twice per day. She also suffers from pain in the upper abdomen, especially when rising from the bed. She is no longer able to care for her 84-year-old husband or her 40-year-old mentally disabled son, who lives with them. She is aware of her poor prognosis but is not able to share her sorrows with her family.

CYP3A4*22 genotype and systemic exposure affect paclitaxel-induced neurotoxicity.

PURPOSE: Paclitaxel is used for the treatment of several solid tumors and displays a high interindividual variation in exposure and toxicity. Neurotoxicity is one of the most prominent side effects of paclitaxel. This study explores potential predictive pharmacokinetic and pharmacogenetic determinants for the onset and severity of neurotoxicity. EXPERIMENTAL DESIGN: In an exploratory cohort of patients (n = 261) treated with paclitaxel, neurotoxicity incidence, and severity, pharmacokinetic parameters and pharmacogenetic variants were determined. Paclitaxel plasma concentrations were measured by high-performance liquid chromatography or liquid chromatography/tandem mass spectrometry, and individual pharmacokinetic parameters were estimated from previously developed population pharmacokinetic models by nonlinear mixed effects modeling. Genetic variants of paclitaxel pharmacokinetics tested were CYP3A4*22, CYP2C8*3, CYP2C8*4, and ABCB1 3435 C>T. The association between CYP3A4*22 and neurotoxicity observed in the exploratory cohort was validated in an independent patient cohort (n = 239). RESULTS: Exposure to paclitaxel (logAUC) was correlated with severity of neurotoxicity (P < 0.00001). Female CYP3A4*22 carriers were at increased risk of developing neurotoxicity (P = 0.043) in the exploratory cohort. CYP3A4*22 carrier status itself was not associated with pharmacokinetic parameters (CL, AUC, Cmax, or T>0.05) of paclitaxel in males or females. Other genetic variants displayed no association with neurotoxicity. In the subsequent independent validation cohort, CYP3A4*22 carriers were at risk of developing grade 3 neurotoxicity (OR = 19.1; P = 0.001). CONCLUSIONS: Paclitaxel exposure showed a relationship with the severity of paclitaxel-induced neurotoxicity. In this study, female CYP3A4*22 carriers had increased risk of developing severe neurotoxicity during paclitaxel therapy. These observations may guide future individualization of paclitaxel treatment.

Systematic monitoring and treatment of physical symptoms to alleviate fatigue in patients with advanced cancer: a randomized controlled trial.

PURPOSE: Several guidelines on the treatment of cancer-related fatigue recommend optimizing treatment of accompanying symptoms. However, evidence for this recommendation from randomized clinical trials is lacking. We investigated whether monitoring and protocolized treatment of physical symptoms alleviates fatigue. PATIENTS AND METHODS: In all, 152 fatigued patients with advanced cancer were randomly assigned to protocolized patient-tailored treatment (PPT) of symptoms or care as usual. The PPT group had four appointments with a nurse who assessed nine symptoms on a 0 to 10 numeric rating scale (NRS). Patients received a nonpharmacologic intervention for symptoms with a score ≥ 1 and a medical intervention for symptoms with a score ≥ 4. Fatigue dimensions, fatigue NRS score, interference of fatigue with daily life, symptom burden, quality of life, anxiety, and depression were measured at baseline and after 1, 2, and 3 months. Differences between the groups over time were assessed by using mixed modeling. RESULTS: Seventy-six patients were randomly assigned to each study arm. Mean age was 58 ± 10 years, 57% were female, and 65% were given palliative chemotherapy. We found significant improvements over time in favor of PPT for the primary outcome general fatigue (P = .01), with significant group differences at month 1 (effect size, 0.26; P = .007) and month 2 (effect size, 0.35; P = .005). Improvements in favor of PPT were also found for the following secondary outcomes: fatigue dimensions "reduced activity" and "reduced motivation," fatigue NRS, symptom burden, interference of fatigue with daily life, and anxiety (all P ≤ .03). CONCLUSION: In fatigued patients with advanced cancer, nurse-led monitoring and protocolized treatment of physical symptoms is effective in alleviating fatigue.

Cut points on 0-10 numeric rating scales for symptoms included in the Edmonton Symptom Assessment Scale in cancer patients: a systematic review.

CONTEXT: To improve the management of cancer-related symptoms, systematic screening is necessary, often performed by using 0-10 numeric rating scales. Cut points are used to determine if scores represent clinically relevant burden. OBJECTIVES: The aim of this systematic review was to explore the evidence on cut points for the symptoms of the Edmonton Symptom Assessment Scale. METHODS: Relevant literature was searched in PubMed, CINAHL®, Embase, and PsycINFO®. We defined a cut point as the lower bound of the scores representing moderate or severe burden. RESULTS: Eighteen articles were eligible for this review. Cut points were determined using the interference with daily life, another symptom-related method, or a verbal scale. For pain, cut point 5 and, to a lesser extent, cut point 7 were found as the optimal cut points for moderate pain and severe pain, respectively. For moderate tiredness, the best cut point seemed to be cut point 4. For severe tiredness, both cut points 7 and 8 were suggested frequently. A lack of evidence exists for nausea, depression, anxiety, drowsiness, appetite, well-being, and shortness of breath. Few studies suggested a cut point below 4. CONCLUSION: For many symptoms, there is no clear evidence as to what the optimal cut points are. In daily clinical practice, a symptom score ≥4 is recommended as a trigger for a more comprehensive symptom assessment. Until there is more evidence on the optimal cut points, we should hold back using a certain cut point in quality indicators and be cautious about strongly recommending a certain cut point in guidelines.

Differences in fatigue experiences among patients with advanced cancer, cancer survivors, and the general population.

CONTEXT: Fatigue is a multidimensional symptom experienced physically, cognitively, and emotionally. Research on fatigue experiences in various stages of cancer might help to elucidate the nature of cancer-related fatigue. OBJECTIVES: To compare fatigue experiences in advanced cancer patients (ACPs), cancer survivors (CSs), and controls from the general population (GenPop). METHODS: Sixty-three ACPs (no antitumor therapy in the last month and no options for future therapy) were matched for age, sex and diagnosis with 63 CSs (last treatment one to five years ago) and 315 controls. Fatigue was measured unidimensionally with the Numeric Rating Scale and multidimensionally with the Multidimensional Fatigue Inventory. RESULTS: All fatigue levels (general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue) were higher in ACPs than in CSs and controls (P<0.01), whereas fatigue levels were not different between CSs and controls. NRS scores in ACPs and CSs were significantly predicted by the fatigue dimensions physical fatigue and mental fatigue only. Although physical fatigue and mental fatigue were strongly related in the GenPop, the relation was weaker in CSs and not significant in ACPs. In multivariate analyses, only physical fatigue differentiated ACPs from CSs and controls (P<0.01). CONCLUSION: ACPs experience fatigue more intensely than CSs and controls when fatigue is measured multidimensionally. Although mental and physical dimensions of fatigue contribute to the overall experience of fatigue in both groups of cancer patients, physical fatigue best differentiated ACPs from both CSs and controls.

Inflammation and fatigue dimensions in advanced cancer patients and cancer survivors: an explorative study.

BACKGROUND: Inflammation may underlie cancer-related fatigue; however, there are no studies that assess the relation between fatigue and cytokines in patients with advanced disease versus patients without disease activity. Furthermore, the relation between cytokines and the separate dimensions of fatigue is unknown. Here, association of plasma levels of inflammatory markers with physical fatigue and mental fatigue was explored in advanced cancer patients and cancer survivors. METHODS: A total of 45 advanced cancer patients and 47 cancer survivors completed the subscales Physical Fatigue and Mental Fatigue of the Multidimensional Fatigue Inventory. Plasma concentrations of C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1-ra), interleukin-6 (IL-6), interleukin-8 (IL-8), and neopterin were measured. Nonparametric tests were used to assess differences in fatigue intensity and levels of inflammatory markers and to determine correlation coefficients between the fatigue dimensions and inflammatory markers. RESULTS: Compared with cancer survivors, patients with advanced cancer had higher levels of physical fatigue (median 16 vs 9, P < .001) and mental fatigue (median 11 vs 6, P = .01). They also had higher levels of all cytokines (P < .01). In advanced cancer, CRP (r = 0.49, P = .001), IL-6 (r = 0.43, P = .003), IL-1-ra (r = 0.32, P = .03), and neopterin (r = 0.25, P = .10) were correlated with physical but not with mental fatigue. In cancer survivors, only IL-1-ra was related to both physical fatigue (r = 0.24, P = .10) and mental fatigue (r = 0.35, P = .02). CONCLUSIONS: In advanced cancer, inflammation seems to be associated with physical fatigue, but not to mental fatigue. In cancer survivors, there was no convincing evidence that inflammation plays a major role in fatigue.

A combined pain consultation and pain education program decreases average and current pain and decreases interference in daily life by pain in oncology outpatients: a randomized controlled trial.

Pain education programs (PEP) and pain consultations (PC) have been studied to overcome patient-related and professional-related barriers in cancer pain management. These interventions were studied separately, not in combination, and half of the studies reported a significant improvement in pain. Moreover, most PEP studies did not mention the adequacy of pain treatment. We studied the effect of PC combined with PEP on pain and interference by pain with daily functioning in comparison to standard care (SC). Patients were randomly assigned to SC (n=37) or PC-PEP (n=35). PEP consisted of patient-tailored pain education and weekly monitoring of pain and side effects. We measured overall reduction in pain intensity and daily interference over an 8-week period as well as adequacy of pain treatment and adherence. The overall reduction in pain intensity and daily interference was significantly greater after randomization to PC-PEP than to SC (average pain 31% vs 20%, P=.03; current pain 30% vs 16%, P=.016; interference 20% vs 2.5%, P=.01). Adequacy of pain management did not differ between the groups. Patients were more adherent to analgesics after randomization to PC-PEP than to SC (P=.03). In conclusion, PC-PEP improves pain, daily interference, and patient adherence in oncology outpatients.