Fentanyl Buccal Tablet vs. Oral Morphine in Doses Proportional to the Basal Opioid Regimen for the Management of Breakthrough Cancer Pain: A Randomized, Crossover, Comparison Study

Mercadante, Sebastiano; Adile, Claudio; Cuomo, Arturo; Aielli, Federica; Cortegiani, Andrea; Casuccio, Alessandra; Porzio, Giampiero

doi:10.1016/j.jpainsymman.2015.05.016

Cited by 44 publications

(31 citation statements)

References 37 publications

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“…This study has confirmed numerous observational trials showing the safety and effectiveness of doses proportional to the basal opioid regimen even in older patients or in patients receiving high doses of opioids [44,[54][55][56][57][58][59][60][61]. More recently, the effectiveness of FBT and oral morphine was compared by using similar doses, proportional to the basal opioid regimen [62], providing an advantage of FBT that was more representative in comparison with previous comparative studies in which the dose of FBT was titrated [37,40]. It is of interest that in a real-world study reflecting clinical practice, the titration process provided doses even higher than those expected by using doses proportional to basal opioid regimen [63].…”

Section: Ninth Commandment: Dosing Btcp Medicationssupporting

confidence: 79%

Breakthrough Cancer Pain: Ten Commandments

Mercadante

Cuomo

2016

Value in Health

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The term "breakthrough cancer pain" (BTcP) was introduced about 25 years ago. Peaks of pain intensity reported in patients with cancer had been invariably examined in the past years, providing relevant information for a better knowledge of this phenomenon and its treatment. The aim of this critical review was to provide the golden rules, namely, the 10 commandments, for a correct diagnostic pathway of BTcP and a consequent personalized pharmacological treatment. These are as follows: 1) assessment of background analgesia, 2) drugs used for background analgesia, 3) BTcP is a frequent phenomenon, 4) characteristics of BTcP, 5) diagnosis of BTcP, 6) continuous assessment, 7) tailored pharmacological treatment of BTcP, 8) selection of BTcP medication, 9) dosing BTcP medications, and 10) education. These steps may help clinicians to recognize and treat BTcP adequately.

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Section: Ninth Commandment: Dosing Btcp Medicationssupporting

confidence: 79%

Breakthrough Cancer Pain: Ten Commandments

Mercadante

Cuomo

2016

Value in Health

Self Cite

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“…5,6) Besides, its analgesic action, morphine has anti-nociceptive effect, and might even change tumor progression. In our earlier study, we found that opioid molecule fentanyl could inhibit the vitality of gastric carcinoma cells and cell cycle progression, the mechanism of which might be associated with inhibition of nuclear factor-kappaB (NF-κB) nuclear translocation and phosphatase and tensin homolog deleted from chromosome 10 (PTEN) tumor suppressor gene upregulation.…”

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confidence: 99%

Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis

Chen

Qin

et al. 2017

Biological & Pharmaceutical Bulletin

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Morphine is widely used for relieving cancer pain in patients with advanced cancer. However, whether morphine can suppress or promote the progression of cancer in breast cancer patients receiving morphine analgesia remains unclear. Therefore, we used an in vitro model treated with morphine and naloxone to investigate the effects of morphine on breast cancer cell line MCF-7. MCF-7 cells were cultured with different concentrations (0.01 to 10 µM) of morphine at 12th, 24th, 36th, 48th, 60th and 72nd hours. Then, cell viability was measured through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell cycle and apoptosis assays were detected by flow cytometry (FCM). In addition, cell proliferation was conducted by colony formation assay. In this study, we have found that morphine (0.01 to 10 µM) could significantly reduce the cell vitality, growth and colony formation rate of MCF-7 cells, which has a certain relationship with cell cycle progression arrested at the G0/G1 and G2/M phase and MCF-7 cells apoptosis. Moreover, naloxone along with morphine could not reverse these effects, which indicates that the inhibition of MCF-7 breast cancer cell growth and proliferation by morphine could be its independent effect, not associated with opioid receptors. Morphine can inhibit cell growth by blocking the cell cycle and promote apoptosis in MCF-7 cells. Hence, morphine may be unable to promote the progression of cancer in breast cancer patients receiving morphine analgesia.Key words apoptosis; breast cancer; cell cycle; MCF-7 cell; morphine Breast cancer (BC) is the most commonly diagnosed cancer among women.1,2) In addition, younger women often present with more aggressive incidence of BC and leading to cause high mortality rate of BC, between the ages of 20 and 59. 3,4) Furthermore, most of the cancer patients are severely stressed by cancer pain, which in turn creates further psychological burden and affects patients outcome. Therefore, cancer pain has increasingly become the major focus of attention and opioids candidates are routinely used to treat cancer pain.Morphine is the representative opioid and is widely used for treatment in advanced cancer. 5,6) Besides, its analgesic action, morphine has anti-nociceptive effect, and might even change tumor progression. In our earlier study, we found that opioid molecule fentanyl could inhibit the vitality of gastric carcinoma cells and cell cycle progression, the mechanism of which might be associated with inhibition of nuclear factor-kappaB (NF-κB) nuclear translocation and phosphatase and tensin homolog deleted from chromosome 10 (PTEN) tumor suppressor gene upregulation. 7) We also demonstrated that morphine could suppress the growth and the cell cycle progression of MGC-803 cells, the mechanism of which might be related to activation of caspase-3 and caspase-9, and inhibition of NF-κB nuclear translocation. 8)Some studies have found that at a clinical concentration morphine (0.01 µM) can induce cell apoptosis or necrosis in MCF-7 human tu...

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“…Studies with other fentanyl transmucosal formulations are consistent with this result, suggesting that choosing the initial dose of a BTCP opioid based on the current ATC dose is not supported by the published data [30,31]. However, there has been a study suggesting doses of a transmucosal immediate-release buccal fentanyl formulation proportional to a patient's ATC opioid regimen was more efficacious than oral morphine during the first 30 min posttreatment [32]. Another approach calculated the dose of a transmucosal immediate-release sublingual fentanyl formulation for BTCP from a precalculated morphine dose for BTCP and found that a conversion ratio of 1/50 provided efficacious analgesia [33].…”

Section: Discussionmentioning

confidence: 86%

Fentanyl sublingual spray for breakthrough cancer pain in patients receiving transdermal fentanyl.

Alberts

Rauck

Parikh³

et al. 2014

JCO

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aim: To investigate the relationship between effective fentanyl sublingual spray (FSS) doses for breakthrough cancer pain (BTCP) and around-the-clock (ATC) transdermal fentanyl patch (TFP). Methods: Adults tolerating ATC opioids received open-label FSS for 26 days, followed by a 26-day double-blind phase for patients achieving an effective dose (100-1600 μg). Results: Out of 50 patients on ATC TFP at baseline, 32 (64%) achieved an effective dose. FSS effective dose moderately correlated with mean TFP dose (r = 0.4; p = 0.03). Patient satisfaction increased during the study. Common adverse events included nausea (9%) and peripheral edema (9%). conclusion: FSS can be safely titrated to an effective dose for BTCP in patients receiving ATC TFP as chronic cancer pain medication. clinicaltrials.gov identifier: NCT00538850 Keywords• breakthrough cancer pain • fentanyl sublingual spray • transmucosal immediate-release fentanyl David S Alberts, MD, and co-authorsPersistent underlying pain in patients with cancer is effectively managed by around-the-clock (ATC) opioid analgesics; however, transient exacerbations of pain that occur spontaneously over the underlying pain, commonly described as breakthrough cancer pain (BTCP), can occur [1,2]. BTCP is reported by 15-100% of patients with cancer depending on the clinical setting and patient population studied [3][4][5][6][7][8][9]. In a systematic review of 19 observational Practice points• Patients with cancer-related pain may require around-the clock (ATC) opioid analgesics.• Despite ATC opioids, breakthrough cancer pain (BTCP) may necessitate the use of additional analgesics.• Fentanyl products such as the transdermal fentanyl patch and fentanyl sublingual spray may be prescribed to manage BTCP.• Treatment of cancer-related pain is complex and requires thorough understanding of the relationship between doses of concomitant medications and their analgesic and adverse effects.• The current study indicates a weak-to-moderate correlation between the effective dose of fentanyl sublingual spray used to treat BTCP and the effective dose of ATC transdermal fentanyl patch.• Initiating treatment with a low dose of a fentanyl sublingual spray and titrating upward to identify an effective dose may be an efficacious strategy for patients receiving ATC transdermal fentanyl patch and fentanyl sublingual fentanyl spray.• Fentanyl sublingual spray is generally well tolerated in patients receiving ATC transdermal fentanyl patch for BTCP.Pain Manag. (Epub ahead of print)

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Fentanyl Buccal Tablet vs. Oral Morphine in Doses Proportional to the Basal Opioid Regimen for the Management of Breakthrough Cancer Pain: A Randomized, Crossover, Comparison Study

Abstract: When used in doses proportional to the basal opioid regimen, FBT showed a clear superiority and was well tolerated when compared with OM during the first 30 minutes, which is the approximate target for a timely intervention required for a BTcP medication.

Cited by 44 publications

References 37 publications

Breakthrough Cancer Pain: Ten Commandments

Breakthrough Cancer Pain: Ten Commandments

Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis

Fentanyl sublingual spray for breakthrough cancer pain in patients receiving transdermal fentanyl.

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