Edoardo Arcuri

Ospedale Sacro Cuore di Gesù, Benevento, Campania, Italy

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Publications (49)148.7 Total impact

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    ABSTRACT: Pain is frequently experienced by patients with hematological malignancies, although it often receives little attention. Different underlying causes and mechanisms may sustain several pain syndromes in hematological malignant patients. Pain may be due to disease itself, to disease-related complications, to iatrogenic causes or may be associated with unrelated medical conditions. The management of pain in this setting requires a multidisciplinary approach, integrating analgesics and causal interventions. An accurate diagnostic assessment and the identification of the underlying causes and pathogenetic mechanisms may dictate the treatment approach. For most pain patients, the WHO's three-step analgesic scale for cancer pain relief can provide adequate relief with oral options, although difficult-to-treat pain syndromes, requiring a more complex treatment approach, may also be observed.
    No preview · Article · Feb 2011 · Expert Review of Hematology
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    ABSTRACT: Data on the treatment of breakthrough cancer pain (BTcP) in patients receiving methadone therapy are lacking. Whether methadone produces tolerance to other opioids, other opioids should be less effective when administered as a BTcP medication. The aim of this preliminary study was to assess the efficacy of fentanyl buccal tablets (FBT) for the treatment of BTcP in patients who receive methadone as a background analgesic. A prospective study was carried out for a period of 1 year in a consecutive sample of 13 advanced cancer patients admitted to an acute pain relief and palliative care unit-patients who were receiving stable doses of oral methadone for their background analgesia. The dose of FBT was 100 μg for patients who were receiving 12 mg of oral methadone. For higher doses of methadone, proportional doses of FBT were given. For each episode, trained nurses collected changes in pain intensity (on numerical scale 0-10) and emerging problems when called for pain increases considered to be severe in intensity by patients) (T0) and 15 min after FBT administration (T15). The mean age was 58.1 (SD 9.9), and nine patients were males. Sixty-four events were treated with FBT (4.9 ± 3.1 for each patient, on average). Patients were receiving mean doses of oral methadone of 68 mg (range 15-240). In the majority of events, a decrease in pain intensity >33% and >50% was observed (n = 20 and n = 26, respectively), 15 min after the administration of FBT. Data on ten episodes were unavailable. Nine events were unsuccessfully treated. In all the patients, the level of adverse effects after FBT administration was mild and undistinguishable from that associated with basal opioid analgesia. FBT was effective as breakthrough pain medication in patients receiving methadone for their background analgesia, confirming that this group of patients are not inevitably resistant to other opioids.
    Full-text · Article · Sep 2010 · Supportive Care in Cancer
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    ABSTRACT: To describe 2 cases in which an abrupt progression of disease compromising pain pathways and inducing some relief of existing pain or limiting drug delivery to central nervous system. Case reports which a significant decrease of opioid requirement was reported, either systematically and spinally. The progression of disease produced changes in pain input or limited the effects of opioids given spinally. The data presented suggest that physicians should be aware of the possibility that opioid doses have to be reduced, where presumably specific events related to the progression of disease can change the pain syndrome or reduce the delivery of opioids when using particular routes of administration. This problem needs to be recognized and treated appropriately when it occurs.
    Full-text · Article · Jan 2010 · The Clinical journal of pain
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    ABSTRACT: To improve opioid repsonse in patients with movement-related pain by using opioid switching adding a burst of ketamine. Two patients with incident bone pain who had adverse effects with increasing doses of opioids were switched to methadone and a burst of 100 mg/d of ketamine for 2 consecutive days was added. Basal pain and pain on movement significantly improved. The development of breakthrough pain due to movement (incident pain), associated with bone metastases is so rapid that no medication as needed has such a short onset to parallel this temporal pattern of pain firing. Experimental studies have shown that bone metastases are characterized by a specific pattern of spinal hyperexcitation requiring higher doses of opioids. Optimization of basal opioid regimen may improve mobilization. However, adverse effects may more likely occur. The role of opioid switching and burst ketamine to further improve the opioid response has never been assessed in this context. Further studies in animals could confirm these preliminary data, with specific design to parallel this clinical context.
    Full-text · Article · Oct 2009 · The Clinical journal of pain
  • Sebastiano Mercadante · Edoardo Arcuri
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    ABSTRACT: The Blood-brain-barrier (BBB) has been found to have multiple functions rather than being a simple anatomic structure. The BBB provides a stable milieu, essential for the complex integrative functions of the CNS, and has also a protective action against potentially damaging neuroactive substances and other neurotransmitters with highly variable changes in systemic extracellular fluids, blocking their entry or actively transforming by hydrolyzing and conjugating enzymes, and removing them from brain via active efflux transporters. A large number of transporters are present in the BBB, most of them being designed to carry polar substances into the brain that would otherwise have minimal access to the CNS. All the observations regarding the unpredictability of traditional factors influencing the drug passage through the BBB may be partially explained by recent investigations regarding membrane-bound drug transporters capable of actively pumping a variety of drugs out of the CNS. The most characterized transporter system is represented by P-glycoprotein (P-gp), a saturable transporting system systemically expressed widely in several tissues, impeding the delivery of therapeutic agents. Many drugs, including opioids, which are potentially effective at their site of action, may have a decreased effect due to a failure to deliver them in sufficient amount to the CNS. Opioid transport is often the result of the concerted action of efflux and uptake pumps located in the BBB. Polymorphisms affecting drug transporters are of interest for opioid analgesia, as altered function or expression of transporters might cause differences in the extracellular brain concentrations of opioids. Given such an important role of P-gp in the drug disposition process, it is not surprising to see increasing interest on the role of polymorphisms in this transporter as a potential determinant of interindividual variability in opioid response.
    No preview · Article · Jan 2009 · Gene therapy & molecular biology
  • Edoardo Arcuri

    No preview · Article · Oct 2008 · Palliative Medicine
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    ABSTRACT: Severe pain syndromes may be recorded during all phases of haematopoietic stem cell transplantation (HSCT) for haematological malignancies: from stem cell mobilization to the long-term post transplant period. Although the major cause of pain in the setting of HSCT is injury to mucosal tissues induced by the conditioning regimen, pain from several other causes has been reported. In this paper, we review pain and its management in the setting of HSCT.
    Full-text · Article · Jun 2008 · Bone Marrow Transplantation
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    ABSTRACT: Adequate and rapid pain control is one of the main goals of cancer pain treatment. The objective of this study was to assess the effect and tolerability of oral normal-release morphine during the initial phase of treatment in patients with moderate-to-severe cancer pain. Consecutive patients naïve to strong opioids received normal-release morphine 5 or 10 mg every 4 h during the titration phase (first 5 days), depending on previous analgesic therapy. Pain intensity was assessed using an 11-point Numerical Rating Scale (0-10), and data were recorded in a patient-compiled diary. The primary endpoint was the proportion of time with pain control (a reduction of at least 50% with respect to the baseline pain score) during the titration phase. A total of 159 consecutive patients (102 men; mean age 65 years) with cancer-related pain were enrolled. Pain control was observed for 75% (95% CI 70-80) of the follow-up period in the intent-to-treat population. Overall, 50% and 75% of patients achieved pain control within 8 and 24 h after starting normal-release morphine therapy respectively. The mean pain score was 7.63 points at baseline, and decreased to 2.43 and 1.67 points (both P<0.001) at days 3 and 5 respectively. The most commonly reported adverse events were somnolence (24% of patients), constipation (22%), vomiting (13%), nausea (10%) and confusion (7%). Normal-release morphine results in rapid and satisfactory pain control, and is well tolerated, during the strong-opioid titration phase in patients with moderate-to-severe cancer pain.
    Full-text · Article · Apr 2008 · Palliative Medicine
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    Sebastiano Mercadante · Edoardo Arcuri
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    ABSTRACT: Existing studies indicate a high prevalence rate and poor management of cancer pain in the elderly. Pain is often considered an expected concomitant of aging, and older patients are considered more sensitive to opioids. Despite the well known pharmacokinetic changes in the elderly, the complex network of factors involved in the opioid response make the evaluation of a single element, such as age, more difficult. Notwithstanding such difficulties, appropriate analgesic treatment is able to control cancer pain in the elderly in most cases. Skills necessary to optimise pain control in older cancer patients include the ability to objectively assess functional age (not necessarily related to chronological age since the rate of decline is variable), understand the impact of coexisting conditions, carefully manage the numbers and types of drugs taken at the same time and adequately communicate with patients and relatives. The most common treatment of cancer pain consists of the use of regularly given oral analgesics. The elderly are at increased risk of developing toxicity from NSAIDs, and the overall safety of these drugs in frail elderly patients should be considered. When older patients have clear contraindications to NSAIDs, manifest signs of toxicity from these agents, or find that pain is no longer controlled with this class of drugs, opioids should be started. A variety of opioids are available, and they differ widely with respect to analgesic potency and adverse effects among the elderly. Although the aged population requires lower doses of opioids, only careful titration based on individual response can ensure the appropriate response to clinical demand. Elderly patients are potentially more likely to be affected by opioid toxicity because of the physiological changes associated with aging. Nevertheless, appropriate dosage and administration may limit these risks. Cancer patients with pain who do not respond to increasing doses of opioids because they develop adverse effects before achieving acceptable analgesia may be switched to alternative opioids. Despite the favourable effects reported with opioid switching, monitoring is crucial, particularly in the elderly or patients who are switched from high doses of opioids. Adjuvant analgesics, including antidepressants, antiepileptics, corticosteroids and bisphosphonates may help in the treatment of certain types of chronic pain. With an appropriate and careful approach, it should be possible to reduce or eliminate unrelieved cancer pain in most elderly patients and, consequently, to enhance their quality of life. Older patients with cancer should be continuously assessed for cancer pain, both before and after analgesic treatment.
    Full-text · Article · Feb 2007 · Drugs & Aging
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    ABSTRACT: Opioids are basic analgesics used in the treatment of moderate to severe pain in patients affected by blood-related malignancies. They should be sequentially administered according to the World Health Organisation scale for cancer pain. Initial treatment and titration with opioids should be based on immediate-release preparations, to be administered at appropriate intervals in order to relieve pain and to satisfy the individual opioid requirement. Once a relatively good pain control has been achieved, a slow release formulation at equivalent doses can be given. Most patients can be adequately managed using oral formulation opioids. However, a small group, such as those presenting severe mucositis or requiring a rapid pain relief, should be managed by intravenous continuous infusion and/or by a patient-controlled analgesia system; while for patients in the community, there are distinct advantages to using the subcutaneous route. Other available routes of administration for opioids, can be used in selected circumstances, including rectal, transdermal, epidural, intrathecal and intramuscular. The invasive neuraxial route has a very limited role in patients with haematological malignancies, given the high risk of infection and bleeding. Through a close observation and a careful management, opioid-related side effects can be effectively prevented and treated. This article reviews the principles of opioid therapy and how opioids can be adapted for patients with pain due to haematological malignancies.
    No preview · Article · Sep 2006 · Annals of Hematology
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    ABSTRACT: Cancer pain can be managed in most patients through the use of the analgesic ladder proposed by the World Health Organization. Recent studies have proposed to skip the second "rung" of the ladder by using a so-called "strong" opioid for moderate pain. However, usual doses of strong opioids commonly prescribed for the third rung of the analgesic ladder may pose several problems in terms of tolerability in opioid-naive patients. The aim of this multicenter study was to evaluate the efficacy and tolerability of very low doses of morphine in advanced cancer patients no longer responsive to nonopioid analgesics. A sample of 110 consecutive opioid-naive patients with moderate-to-severe pain were given oral morphine at a starting dose of 15 mg/day (10 mg in those older than 70 years). Doses were then titrated according to the clinical situation. Pain intensity, morphine doses, symptom intensity, quality of life, and the requirement for dose escalation were monitored for a period of 4 weeks. The treatment was effective and well tolerated by most patients, who were able to maintain relatively low doses for the subsequent weeks (mean dose 45 mg at Week 4). Only 12 patients dropped out due to poor response or other reasons. The use of very low doses of morphine proved to be a reliable method in titrating opioid-naive advanced cancer patients who were also able to maintain their dose, in a 4-week period, below the dose level commonly used when prescribing strong opioids.
    Full-text · Article · Apr 2006 · Journal of Pain and Symptom Management
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    ABSTRACT: Patients who experience a poor response to different systemic opioid trials (oral and intravenous) are candidates for spinal treatment. Breakthrough pain occurring in this group of patients is challenging for physicians. This phenomenon has never been described in this context and the treatment is quite difficult, as patients already demonstrated a poor response to systemic opioids. We report a preliminary experience of alternative methods, including the intrathecal injection of local anesthetic boluses as needed, or alternatively, the use of sublingual ketamine. Twelve consecutive patients with advanced cancer and pain were selected for intrathecal treatment after receiving different trials with systemic opioids. During intrathecal therapy, pain flares not responding to high doses of intravenous morphine were treated with intrathecal boluses of local anesthetics titrated to achieve the best balance between analgesia and adverse effects, or with sublingual ketamine (25 mg), according to their preference. Pain and symptoms were recorded for each episode of breakthrough pain during hospital admission. Effective pain control was achieved in all the episodes treated within 10 minutes with either method, without relevant complications. A mean volume of 0.6 mL of levobupivacaine (LB) 0.25% (1.5 mg) was effective within a few minutes and was well tolerated in patients receiving a continuous intrathecal infusion of a combination of morphine and LB in different doses. Similarly, ketamine in doses of 25 mg sublingually was effective and relatively well tolerated. Despite the difficult clinical situation of these patients, these approaches controlled almost all breakthrough pain events previously unresponsive to relatively high doses of intravenous opioids. These intensive treatments should be reserved for a very selected population and initiated in an appropriate setting with frequent monitoring facilities and skilled nursing.
    Full-text · Article · Dec 2005 · Journal of Pain and Symptom Management
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    ABSTRACT: Tramadol is commonly used as second step drug of the analgesic ladder. In circumstances where the oral route is unavailable, rectal administration of opioids might be a simple alternative. The aim of this study was to compare the analgesic activity and tolerability of tramadol by oral and rectal administration in a double-blind, double-dummy crossover trial. The study included 60 cancer patients with cancer pain no longer responsive to non-opioid drugs. Each patient initially received oral tramadol 50 mg (drops), followed by tramadol sustained release 100 mg orally, and placebo rectally, or tramadol 100 mg rectally and placebo orally, twice a day, in a randomized sequence, on each of 3 days. Patients were allowed to take 50 mg of oral tramadol by drops as needed (four doses per day, to a maximum of 400 mg/day, including the basal dose given by the oral or rectal route). Pain intensity and relief and symptom scores were recorded every day and at the end of each phase of the crossover. The mean age of the patients was 66.1 years (SD 13.5 years); 36 were female, and 44 completed both periods. Patients dropped out due to adverse effects (15 patients) and refusal (1 patient). No differences in the use of rescue dose of oral tramadol were observed between the groups. No differences in pain intensity and relief scores, or in other symptoms between the two treatments were observed. No differences in treatment efficacy as judged by the clinician (P=0.73), in patient compliance (P=0.35), or in patient satisfaction regarding treatment (P
    Full-text · Article · Sep 2005 · Supportive Care Cancer
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    Sebastiano Mercadante · Edoardo Arcuri
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    ABSTRACT: Opioids, intended to abolish pain, can unexpectedly produce hyperalgesia, particularly during rapid opioid escalation. Opioid switching could be a therapeutic option in a condition of opioid-induced tolerance or hyperalgesia, but conversion ratios between opioids are difficult to apply in this context and require strict surveillance and expertise. This situation is challenging, because the rapid escalation of opioid doses, possibly due to the development of opioid-induced tolerance, can cause hyperalgesia. To avoid this adverse effect, clinicians need to refine their assessment of pain treatment and consider opioid switching. The authors present a case report in which switching from fentanyl to methadone was effective in a patient who developed hyperalgesia as a consequence of a rapid opioid escalation. Regardless of the expected clinical improvement of opioid switching using lower doses of the second opioid, the final dose of the second opioid was exaggeratedly low, probably as a consequence of the disappearance of hyperalgesia induced by the first opioid. The results of this case and others like it may help practitioners develop a meaningful approach during opioid escalation, possibly anticipating the need for opioid switching or other alternative measures for patients with uncontrolled cancer pain.
    Full-text · Article · Jul 2005 · American Journal of Hospice and Palliative Medicine
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    Full-text · Article · Jun 2005 · Anesthesia & Analgesia
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    ABSTRACT: The majority of patients with haematologic neoplasias may experience troublesome symptoms and complicating clinical syndromes throughout all phases of disease. In this view, the patientís management should incorporate causal treatments and symptomatic measures. Therefore, among the current concepts concerning the comprehensive management of patients with haemato- logical malignancies, palliative care should exert a more ever expanding role, although only scanty information are available on this topic. In this review we summarize the current knowledge deriving from the pertinent literature and give some recommendation on the symptoms management based on current guidelines and on the judgement of a group of haematologists and of a skilled algologist, all involved for a long time in this clinical setting.
    No preview · Article · Apr 2005 · HAEMA
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    ABSTRACT: We have observed that treatment of human glioma cells with morphine in the nanomolar range of concentration affects the mitochondrial membrane potential. The effect is specific to morphine and is mediated by naloxone-sensitive receptors, and is thus better observed on glioma cells treated with desipramine; moreover, the mitochondrial impairment is not inducible by fentanyl or methadone treatment and is prevented by the nitric oxide (NO) synthase inhibitor L-NAME. We conclude that in cultured glioma cells, the morphine-induced NO release decreases the mitochondrial membrane potential, as one might expect based on the rapid inhibition of the respiratory chain by NO. The identification of new intra-cellular pathways involved in the mechanism of action of morphine opens additional hypotheses, providing a novel rationale relevant to the therapy and toxicology of opioids.
    Full-text · Article · Jan 2005 · Cellular and Molecular Life Sciences CMLS
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    ABSTRACT: Prospective clinical study to evaluate patients suffering from solid tumor using a totally implanted venous access device (TIVAD) to determine: (1) if there is a relationship between cutaneous contamination at port insertion site and catheter-related bloodstream infection (CRBI); (2) development modalities of CRBI; (3) if there is a relationship between chemotherapy administration modalities by push/ bolus versus continuous infusion and CRBI. We studied 41 consecutive patients who needed a TIVAD positioned for chemotherapy administration by bolus/ push or continuous infusion. In every patient, we performed blood cultures from blood samples from port catheters and cutaneous cultures from cutaneous tampons of the skin surrounding the implant area on the first (T0) and eight day (T1) postoperatively, after 1 month (T2), and after 3 months (T3) from insertion. The study was completed on 40 patients; in one case, the port was removed at T2 for septic complications. We obtained four positive blood cultures (two, 5%), two in the same patient, all caused by staphylococcus. Positive cutaneous tampons were 21 (13%) in 11 patients (27%); the four CRBI occurred in this group of patients with none in the remaining 30 patients (73%) for a total number of 120 tampons (p<0.01). In two cases, the same germ was isolated from both the skin and blood. None of the patients presented a local infection of the subcutaneous pocket. Positive cutaneous cultures decrease over time: T0-T2; 24-5%; T1-T3, 20-5% (p<0.04). There were no differences in CRBI incidence and positive cutaneous tampons between the two chemotherapy administration modalities. Cutaneous microbial flora has a primary role in CRBI development within TIVADs; there is a relationship between cutaneous colonization and CRBI; colonization reaches its maximum during the first days after catheterization in which the use of the system is at high risk; colonization occurs both via extraluminal and endoluminal routes; there is no difference in CRBI incidence between bolus and continuous infusion administration.
    No preview · Article · Nov 2004 · Supportive Care Cancer
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    ABSTRACT: To determine the analgesic effect of the addition of gabapentin to opioids in the management of neuropathic cancer pain. One hundred twenty-one consecutive patients with neuropathic pain due to cancer, partially controlled with systemic opioids, participated in a multicenter, randomized, double-blind, placebo-controlled, parallel-design, 10-day trial from August 1999 to May 2002. Gabapentin was titrated from 600 mg/d to 1,800 mg/d in addition to stable opioid dose. Extra opioid doses were available as needed. Zero to 10 numerical scale was used to rate average daily pain. The average pain score over the whole follow-up period was used as main outcome measure. Secondary outcome measures were: intensity of burning pain, shooting/lancinating pain, dysesthesias (also scored on 0 to 10 numerical scale), number of daily episodes of lancinating pain, presence of allodynia, and daily extra doses of opioid analgesics. Overall, 79 patients received gabapentin and 58 (73%) completed the study; 41 patients received placebo and 31 (76%) completed the study. Analysis of covariance (ANCOVA) on the intent-to-treat population showed a significant difference of average pain intensity between gabapentin (pain score, 4.6) and placebo group (pain score, 5.4; P =.0250). Among secondary outcome measures, dysesthesia score showed a statistically significant difference (P =.0077; ANCOVA on modified intent-to-treat population = 115 patients with at least 3 days of pain assessments). Reasons for withdrawing patients from the trial were adverse events in six patients (7.6%) receiving gabapentin and in three patients receiving placebo (7.3%). Gabapentin is effective in improving analgesia in patients with neuropathic cancer pain already treated with opioids.
    No preview · Article · Aug 2004 · Journal of Clinical Oncology
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    Full-text · Article · Aug 2004 · Journal of Pain and Symptom Management

Publication Stats

1k Citations
148.70 Total Impact Points

Institutions

  • 2010
    • Ospedale Sacro Cuore di Gesù
      Benevento, Campania, Italy
  • 1994-2010
    • Istituto Regina Elena - Istituti Fisioterapici Ospitalieri
      • S.C. Laboratorio "C" Oncogenesi Molecolare
      Roma, Latium, Italy
  • 2003-2009
    • CRO Centro di Riferimento Oncologico di Aviano
      Aviano, Friuli Venezia Giulia, Italy
  • 2004
    • San Raffaele Scientific Institute
      Milano, Lombardy, Italy
  • 2002
    • La Maddalena Cancer Center
      Palermo, Sicily, Italy
  • 1995-2001
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      Meldola, Emilia-Romagna, Italy
  • 2000
    • Samot
      San Paulo, São Paulo, Brazil