Psychological distress of patients with advanced cancer: influence and contribution of pain severity and pain interference.

The growing interest in the psychological distress and the multidimensionality of pain in patients with cancer has been the major reason for the conduction of this study. The aims were to evaluate psychological distress and pain in patients with advanced cancer and the impact of pain severity and pain interference dimensions on the anxiety and depression. One hundred twenty patients with advanced cancer were surveyed at a palliative care unit in Athens, Greece. Greek versions of the Hospital Anxiety and Depression (G-HAD) scale and the Brief Pain Inventory were administered. Information concerning patients' treatment received was acquired from the medical records, whereas physicians recorded their clinical condition. The analysis showed that significant associations were found between pain interference to "mood" and HAD-A (anxiety) (r = 0.252, P = .005) and between pain interference to "relations with other people" and HAD-A (r = 0.474, P < .0005). Multiple regression analyses showed that "average pain" (P < .05), pain interference to "walking ability" (P < .05), "normal work" (P < .05, and "relations with other people" are significant predictors of HAD-anxiety (HAD-A) (P < .0005), explaining 46.2% of total variance. For depression (HAD-D), the Greek version of the Brief Pain Inventory dimension that serve as predictor is "enjoyment of life," as well as the demographic variables of "age," and "gender" (P < .05), explaining 22.2% of variance. Moreover, a further analysis of the pain severity and pain interference scales showed that they differentiate the anxiety of the patients with cancer. In this patient sample, pain interference and, to a lesser extent, pain severity was significantly associated with psychological distress (anxiety and pain), whereas pain interference to "walking ability," "normal work," and "relations with other people" was found to be more prominent and troublesome to patients' anxiety than that to patients' depression.

Octreotide long-acting formulation (LAR) in chronic loperamide-refractory diarrhea not related to cancer treatment.

OBJECTIVE: The effectiveness and improvement in quality of life (QOL) of a long-acting formulation of octreotide (LAR) administration for cancer patients, with chronic loperamide-refractory diarrhea not attributed to medical therapy, were investigated. PATIENTS AND METHODS: Twenty-nine patients with chronic loperamide-refractory diarrhea were enrolled to receive octreotide LAR at a starting dose of 30 mg i.m. every 28 days until resolution of the diarrhea for a period of 3 months. RESULTS: Twenty-three patients (79.3%) administered octreotide LAR achieved resolution of diarrhea, while six patients (20.7%) successfully controlled their diarrhea during the study. All patients experienced improved sodium, potassium, albumin and total protein values with improvement in their QOL, as assessed by the Linear Analog Scale Assessment (LASA) (mean values at baseline and at 3 months: energy: 3.2+/-1.1 vs. 6.2+/-1.4; function: 3.1+/-1.3 vs. 6.2+/-1.2; QOL: 3.2+/-0.9 vs. 6.1+/-1.4). No toxicities associated with the administration of octreotide LAR were noted. CONCLUSION: The administration of octreotide LAR at a starting dose of 30 mg i.m. every 28 days efficiently resolved or controlled chronic loperamide-refractory diarrhea, not caused by medical intervention, in cancer patients and improved their QOL.

Oral transmucosal fentanyl citrate: overview of pharmacological and clinical characteristics.

Oral transmucosal fentanyl citrate (OTFC; brand name Actiq, Cephalon, UT) is a new opioid formulation that incorporates fentanyl into a lozenge and allows drug delivery through the buccal mucosa. This kind of absorption avoids first-pass metabolism, yielding a bioavailability substantially greater than oral administration. OTFC has a rapid onset of action and a short duration of effect. These characteristics, which resemble the course of a typical breakthrough pain episode, resulted in making OTFC the first opioid analgesic formulation specifically developed and approved for control of breakthrough pain in cancer patients. Apart from that, OTFC has been used in a variety of clinical situations of noncancer pain. This review article presents the synthesis; clinical pharmacology; pharmacokinetic and pharmacodynamic properties, toxicity, and clinical efficacy of this novel agent.

A prospective randomized controlled clinical trial of zoledronic acid for bone metastases.

In this study, we assessed the safety, tolerability, and effectiveness of two therapeutic regimens relating to the frequency of zoledronic acid (ZOL) infusion. Sixty adult patients with bone metastases were randomly assigned to two study groups. The first group (group A) received 4 mg ZOL every two weeks, and the second group (group B) received 4 mg ZOL every four weeks. Assessment measures included C-telopeptide (CTX) rate, the Greek Brief Pain Inventory (GBPI), the linear analogue scale assessment (LASA) of quality of life, and biochemical markers. Assessments were made at weeks 12, 24, 36, and 48. Clinical endpoints included effective decrease in bone resorption markers, pain relief and improvement of mobility status. The follow-up period was 48 weeks. No statistically significant differences between groups A and B were found in overall profile of biochemical markers, Eastern Cooperative Oncology Group (ECOG) performance status, and GBPI score at the end of the follow-up period. Assessment of bone metastases revealed a slight difference between the two groups, however this difference was not statistically significant. These findings indicate that administering zoledronic acid at four rather that two weeks has no significant impact on overall outcome.

Demographic and clinical predictors of preparatory grief in a sample of advanced cancer patients.

BACKGROUND: Preparatory grief encompasses grief for losses that have already occurred, are currently being experienced, and losses that will or might ensue in the future after the death, as a consequence of it. AIM: To examine the relative contribution of demographic and clinical variables in predicting cancer patients' preparatory grief as recorded from the Preparatory Grief in Advanced Cancer Patients (PGAC) scale. Moreover, researchers were interested in determining whether these dimensions were independently and uniquely associated with preparatory grief. METHODS: Two hundred advanced cancer patients treated in a Pain Relief and Palliative Care Unit completed the PGAC scale, while researchers recorded data on demographic characteristics, disease status and treatment regimen. RESULTS: The analyses showed that the most significant correlations were found between preparatory grief and age (r = -0.227, p = 0.001), gender (p = 0.006), family status (p = 0.019), performance status (p = 0.010), surgery (p = 0.029), opioids (p = 0.019), and diagnosis (p = 0.038). In the prediction of preparatory grief, the contribution of age, performance status, history of other surgery, gender and opioids is high. CONCLUSIONS: Awareness of the specific patients' demographic and medical characteristics, such as old age, poor performance status, history of other surgery, female gender, and strong opioids, contribute to the prediction of patients' preparatory grief.

The role of physical and psychological symptoms in desire for death: a study of terminally ill cancer patients.

The current study assessed the attitudes of the desire for hastened death in terminally ill cancer patients and whether these are determined by their physical and psychological symptoms. The final sample consisted of 106 terminally ill cancer patients attending a Palliative Care Unit, in University of Athens, Greece, between June and October 2004. Significant associations were found between the desire for hastened death (D.H.D.) and 'pain' (r=0.469, p<0.005), 'fatigue' (r=0.591, p<0.0005), 'loss of appetite' (r=0.622, p<0.0005) and 'feeling sad' (r=0.635, p<0.0005). Statistically significant associations were also found between Schedule of Attitudes towards Hastened Death (SAHD) scores, age (r=0.300, p=0.002) and ECOG (p<0.0005). Twenty-six percent of the patients reported high D.H.D. while 41% reported moderate desire. In the prediction of SHAD the contribution of 'pain' (p=0.011), 'lack of appetite' (p=0.012) and 'sadness' (p=0.011) is high (42% of variance). Further findings suggest that D.H.D. is significantly related to 'feeling sad', 'lack of appetite', 'pain' and 'fatigue' after controlling for age, gender and performance status according to ECOG in terminally ill cancer patients.

Prostate cancer presenting with normal serum PSA levels and boney metastases treated with zoledronic acid.

Prostate specific antigen (PSA) is currently the most widely used tumor marker for diagnosing and monitoring prostate cancer. Serum PSA level greater than 10 ng/mL is considered a negative predictor for the presence of bone metastases and routine use of bone scans is therefore avoided. This report describes two cases of patients presenting with normal PSA levels (0-4 ng/ mL) and positive bone scans. The value of routine use of bone scintigraphy in the follow up of these cases is therefore questioned here. Moreover the addition of bisphosphonates to the androgen deprivation treatment, achieved not only pain relief and improvement in aspects of quality of life, but also provided radiographic evidence of management of metastatic bone disease.

Evaluation of epoetin supplemented with oral iron in patients with solid malignancies and chronic anemia not receiving anticancer treatment.

OBJECTIVE: To evaluate the effectiveness and improvement in quality of life (QOL) of epoetin alfa administration supplemented with oral iron as a therapeutic regimen for patients with solid malignancies and anemia of chronic disease (ACD), not receiving chemotherapy and/or radiotherapy. PATIENTS AND METHODS: A total of 100 patients with cancer-related anemia, not subjected to chemotherapy and/or radiotherapy, were randomized to receive for a maximum of 24 weeks either oral iron, equivalent to 200 mg elemental iron once daily, or epoetin alfa 40,000 IU subcutaneously once weekly plus oral iron once daily. RESULTS: Patients in the epoetin alfa group had, from baseline to study end, a mean increase in hemoglobin (Hb) levels of 2.4 g/dL, whereas in the control group the mean Hb level decreased by 0.1 g/dL, (p<0.001). Improvement in QOL as assessed by the LASA and the FACT-An questionnaire were greater in patients in the epoetin alfa group than in the control group (mean change, LASA-energy level: 30.4 mm vs. 0.4 mm, -daily activities: 31.7 mm vs. 0.4 mm, -overall well-being. 32.4 mm vs. 4.9, FACT-An: 43.3 vs. 13.4, respectively). As for ECOG score, patients in the epoetin alfa group had a mean improvement of 0.16 from baseline to study end (control group: 0.06). Improvement in QOL parameters and in ECOG scores correlated positively with increased hemoglobin levels. CONCLUSION: Our results suggest that weekly epoetin alfa therapy supplemented with daily oral iron increases Hb levels and improves QOL in patients with solid malignancies and ACD who are not receiving chemotherapy and/or radiotherapy. This regimen offers optimal therapy in this population taking into consideration physician's convenience and patient's compliance.

Approaches to managing bone metastases from breast cancer: the role of bisphosphonates.

Conventional management of metastatic bone disease involves local and systemic therapies in various combinations, along with symptomatic management to provide optimal care. In recent years, it has become clear that adding bisphosphonates to these treatments reduces the incidence and severity of skeletal complications. Bisphosphonates can also relieve metastatic bone pain and improve quality of life, although the extent to which they have demonstrated these effects may differ between agents. While bisphosphonates are the standard of care for the treatment of bone metastases, clinical trials are investigating additional indications for these agents, including the use of intensive dosing regimens for the relief of severe or opioid-resistant metastatic bone pain and adjuvant treatment for the prevention of bone metastases and cancer treatment-induced bone loss. Current and future indications demand effective, well-tolerated and convenient bisphosphonates, and the benefits of different drugs must be balanced against their limitations. The cost-effectiveness of bisphosphonate treatment is also a consideration, given the high economic burden of metastatic bone disease from breast cancer.

Pain and desire for hastened death in terminally ill cancer patients.

The purpose of this study was to assess the relationship between pain and the desire for hastened death in terminally ill cancer patients. The participants were 120 terminally ill cancer patients under palliative treatment from June 2003 to November 2004. Patients completed a pain assessment tool, the Greek Brief Pain Inventory (G-BPI), and a self-report measure of the desire for hastened death, the Greek Schedule of Attitudes Toward Hastened Death (G-SAHD). Moderate but statistically significant associations were found between some of the severity and interference items of G-BPI and G-SAHD; more specifically, between G-SAHD and G-BPI3, "worst pain in the last 24 hours" (r = 0.279, P = .002); G-SAHD and G-BPI4, "least pain in the last 24 hours" (r = 0.253, P = .005); and G-SAHD and G-BPI5, "average pain in the last 24 hours" (r = 0.283, P = .002). A stronger association was revealed between G-SAHD and G-BPI8, "relief provided by pain treatment and medications in the last 24 hours" (r = -0.326, P = .000). Multiple regression analyses including the enter model and the forward model were conducted. According to the enter model, the strongest predictors of hastened death were items G-BPI6, "current pain"; G-BPI8, "relief provided by pain treatment and medications in the last 24 hours"; G-BPI9i, "interference of pain in general activity"; and G-BPI9iii, "interference of pain in walking." According to the forward model, significant predictors of the desire for death were items G-BPI5, "average pain in the last 24 hours"; G-BPI6, "current pain"; G-BPI9i, "interference of pain in general activity"; and G-BPI9ii, "interference of pain in mood," all of which were statistically significant (P = .000-.042). Pain appeared to have a statistically significant relationship with the desire for hastened death. Effective treatment by healthcare professionals should be provided to reduce pain and cancer-related symptoms as well as the desire for hastened death.

Desire for death near the end of life: the role of depression, anxiety and pain.

OBJECTIVE: This study evaluated the desire of patients with advanced cancer for hastened death to determine its relationship to psychological distress, anxiety and pain. METHODS: One hundred twenty terminally ill cancer patients were surveyed from June to November 2003 at a palliative care unit in Athens, Greece. Greek versions of the Schedule of Attitudes Toward Hastened Death (G-SAHD), the Hospital Anxiety and Depression Scale (G-HADS) and the Brief Pain Inventory were administered. RESULTS: Significant correlations were seen between desire for hasten death and HADS-Depression (r=.605; P<.0005) and HADS-Anxiety (r=.636; P<.0005) scores. Results of multiple regression analyses showed that the HADS-Depression scale (B=.443; P<.0005) as well as the HADS-Anxiety scale (B=.326; P<.0005) and the interaction between HADS-Depression and opioids (B=-.159; P=.012), but not pain intensity, pain-related interference, age, sex, patient's performance status as defined by the Eastern Cooperative Oncology Group as well as the interactions between average pain and opioids and average pain and HADS-Depression, were significant predictors of G-SAHD scores. CONCLUSIONS: In terminally ill cancer patients, depression and anxiety as well as the interaction between HADS-Depression and opioids appeared to have a significant impact on the desire for hastened death while pain does not. Effective management of psychological symptoms seems to be an important aspect of adequate palliative care in order to reduce the desire for hastened death.

Randomized, open label, prospective study on the effect of zoledronic acid on the prevention of bone metastases in patients with recurrent solid tumors that did not present with bone metastases at baseline.

OBJECTIVES: Bisphosphonates have been used successfully in the treatment of hypercalcemia and to reduce skeletal-related complications of bone metastases. Recent in vitro and in vivo evidence suggest that they may also have direct antitumor effects via induction of apoptosis, inhibition of the invasive potential of tumor cell lines in vitro, inhibition of angiogenesis, and reduction in tumor growth indirectly via effects on accessory cells. This is a randomized, open label, prospective study that examined the effect of preventive zoledronic acid treatment on the development of bone metastases in patients with recurrent solid tumors, without bone metastases at the time of randomization. METHODS: Forty patients with recurrent or metastatic advanced cancer, without bone metastases, were randomized into the trial to either receive zoledronic acid or no treatment. Patients were followed up until bone metastases were established. RESULTS: The percentage of patients being bone metastases free at 12 mo was 60% in the zoledronic acid and 10% in the control group (p<0.0005), while the percentages at 18 mo were 20% and 5% respectively (p=0.0002). CONCLUSIONS: The results have shown that bisphosphonates as adjuvant treatment might be useful for the prevention of bone metastases; however, there is need for blinded randomized data before such an approach would be confirmed. In the meantime preventive use of bisphosphonates in patients without any bone metastases should not be used outside the scope of a clinical trial.

Oral transmucosal fentanyl citrate for the treatment of breakthrough pain in cancer patients: an overview of its pharmacological and clinical characteristics.

Breakthrough pain is a transitory flare of pain occurring in most cancer patients against a background of otherwise controlled persistent pain. Treatment of breakthrough pain is a challenging phenomenon. Oral transmucosal fentanyl citrate (Actiq, Cephalon, Inc, West Chester, PA), a new opioid formulation with a unique delivery system, reflects the characteristics of breakthrough pain (rapid onset of action and short duration), making it an effective treatment for cancer patients who already receive opioids and experience flares of pain. This review article aims to present the role of oral transmucosal fentanyl citrate in the management of breakthrough pain in cancer patients. In particular, it is going to discuss the synthesis, clinical pharmacology, pharmacokinetic and pharmacodynamic properties, toxicity, and clinical efficacy of this novel agent.

Life before death: identifying preparatory grief through the development of a new measurement in advanced cancer patients (PGAC).

GOALS OF WORK: This paper describes the development of a self-rating scale to measure preparatory grief in advanced cancer patients. PATIENTS AND METHODS: The Preparatory Grief in Advanced Cancer patients (PGAC) instrument incorporates seven multi-items scales. The final sample consisted of 200 patients. The questionnaire was completed at baseline and 3 days later with a cross-validation sample of 100 patients. MAIN RESULTS: The average time required to complete the questionnaire was 9 min. All scales met the minimum standards of reliability (Cronbach's alpha coefficient >0.70). The test-retest reliability in terms of Spearman-rho coefficient was also satisfactory (p < 0.05). Validity was demonstrated by content validity, factor analysis, convergence and discriminative validity, inter-scales correlations, concurrent validity with the Hospital Anxiety and Depression Scale (HADS) and known-group validity with the Eastern Cooperative Oncology Group (ECOG) performance status. CONCLUSIONS: The PGAC is a reliable and valid measure for the assessment of anticipatory grief in patients with advanced stage cancer.

The evolution of euthanasia and its perceptions in Greek culture and civilization.

Death has preoccupied humanity since before the dawn of civilization. As a multidimensional and moral problem, the end of life has concerned different civilizations, and different approaches to euthanasia, or "good death," have been developed in each culture. In Greece, there is a long record of the culture's evolving attitudes toward death and euthanasia.A more widespread knowledge of the views and traditions surrounding the act of euthanasia can contribute to a better understanding of the controversies surrounding modern attitudes and practice.

Oral transmucosal fentanyl citrate for the treatment of breakthrough pain in cancer patients: an overview of its pharmacological and clinical characteristics.

Breakthrough pain is a transitory flare of pain occurring in most cancer patients against a background of otherwise controlled persistent pain. Treatment of breakthrough pain is a challenging phenomenon. Oral transmucosal fentanyl citrate (OTFC; brand name Actiq, Chephalon Inc., West Chester, PA), a new opioid formulation with a unique delivery system, reflects the characteristics of breakthrough pain (rapid onset of action and short duration), making it an effective treatment for cancer patients who already receive opioids and experience flares of pain. This review article aims to present the role of oral transmucosal fentanyl citrate in the management of breakthrough pain in cancer patients. In particular, it is going to discuss the synthesis, clinical pharmacology, pharmacokinetic and pharmacodynamic properties, toxicity, and clinical efficacy of this novel agent.

Comparison of transdermal fentanyl with codeine/paracetamol, in combination with radiotherapy, for the management of metastatic bone pain.

Radiotherapy (R/T) is frequently used for palliative treatment of painful bone metastases; however, complete alleviation of pain is not always achieved. This study was designed to evaluate pain management outcomes and quality of life (QoL) measures in cancer patients with metastatic bone pain receiving a combination of R/T and either transdermal therapeutic fentanyl (TTS-F) patches or codeine/paracetamol. A total of 460 palliative care patients with bone metastases who received R/T were enrolled in this prospective, open-label study. The patients were randomized to initially receive a total dose of 120 mg codeine/paracetamol per day or TTS-F patches releasing 25 microg fentanyl per hour. Pain measures were assessed on the basis of selected questions from the Greek-Brief Pain Inventory. Overall treatment satisfaction (scale, 1 to 4), QoL, and European Collaborative Oncology Group status were also recorded. Among the 460 patients, 422 were eligible for evaluation. Pain measures in the TTS-F group demonstrated statistically significant improvements during the study that were superior to those in the codeine/paracetamol group (p < 0.05). Likewise, there was a significantly greater increase (p < 0.05) in the mean satisfaction score for patients in TTS-F group at every visit between baseline and month two. The vast majority (95.8 percent) of patients in the codeine/paracetamol group increased their medication dosage until the end of the study, whereas in the TTS-F group the respective percentage was only 6.1. Both treatments were generally well tolerated, with constipation as the most common side effect followed by sleep disturbances and nausea. The overall frequencies of side effects were higher in the codeine/paracetamol group. The results therefore indicate that TTS-F offers more effective pain relief than codeine/paracetamol, in combination with R/T, in patients with metastatic bone pain, obtaining complete treatment satisfaction matched by improvements in their QoL.

Psychometric analyses of the Mental Adjustment to Cancer (MAC) scale in a Greek palliative care unit.

The purpose of the study was to assess the Mental Adjustment to Cancer (MAC) scale on a heterogeneous Greek sample of 200 advanced cancer patients. The results presented regard the validation analysis of the Greek version. The homogeneity of the original subscales proved to be satisfactory (alpha coefficients ranged from 0.81 to 0.91). A factor analysis was carried out using the LISREL 8.3 procedure. This yielded five factors, including 25 of the 40 original items (alpha coefficients 0.62-0.93). The resulting factors were called 'hopeless', 'positive attitude', 'acceptance', 'mental engagement', and 'fatalistic'. Correlations between the MAC scale and the disease severity as measured by the ECOG performance status have shown difference only between patients with 'good' versus 'poor' performance status in the 'hopeless' scale (p=0.047). The results suggest that the Greek version, as measured in advanced cancer patients attending a palliative care unit, is a reliable and valid clinical tool in Greece.

Influence of pain and quality of life on desire for hastened death in patients with advanced cancer.

OBJECTIVE: to assess the relationship between quality of life, pain and desire for hastened death in advanced cancer patients. METHODS: 120 Greek patients with advanced cancer were interviewed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 version 3.0 (EORTC QLQ-C30), the Greek Brief Pain Inventory (G-BPI), the Greek Hospital Anxiety and Depression Scale (G-HADS) and the Greek Schedule of Attitudes toward Hastened Death (G-SAHD). RESULTS: statistically significant associations were found between total G-SAHD scores and scores for the worst level of pain in the previous 24 hours (G-BP13) (r = 0.279, P = 0.002), and between total G-SAHD scores and scores for the level of pain relief obtained in the last 24 hours (G-BP18) (r = -0.326, P = 0.0005). The strongest correlations were found between G-SADH and emotional functioning (r = 0.569, P<0.0001) and global quality of life (r = -0.331, P<0.0001) from EORTC QLQ-C30. In multivariate analyses, emotional functioning, social functioning, financial impact, and the interference of pain in general activity and mood were significant predictors of G-SAHD (all P<0.0001). CONCLUSION: quality of life and pain appeared to have a statistically significant relationship with desire for hastened death. Adequate palliative care should alleviate pain and the desire for hastened death, improving quality of life.

Greek M.D. Anderson Symptom Inventory: validation and utility in cancer patients.

OBJECTIVE: The M.D. Anderson Symptom Inventory (MDASI) is a brief assessment of the severity and impact of cancer-related symptoms. The purpose of this study was the translation and validation of the questionnaire in Greek (G-MDASI). METHODS: The translation and validation of the assessment took place at a Pain Relief and Palliative Care Unit. The final validation sample included 150 cancer patients (61 males, 89 females, age range 31-88 years, mean age 63.32). The patients completed the questionnaires at the outpatient clinic. Assessing the validity and reliability constituted the actual validation of the G-MDASI. RESULTS: The item 'diarrhea' had a score of 0 in 139 patients and, thus was omitted from the 'core' list. Consequently, the core questionnaire consisted of 14 items. Factor analysis resulted in a 3-factor model, in both validation and cross-validation samples. The examination of the sensitivity of the MDASI revealed that there were differences between patients with poor-to-good performance status but no differences were found between patients in different treatment groups. CONCLUSIONS: The results showed that the G-MDASI is a reliable and valid measure in Greek cancer patients. It has proved to be a comprehensive symptom assessment tool.