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Tolerability of sublingual fentanyl tablets for the treatment of breakthrough cancer pain in patients aged ≥65 years: pooled analysis from 2 clinical trials
Abstracts (300) Tolerability of sublingual fentanyl tablets for the treatment of breakthrough cancer pain in patients aged $65 years: pooled analysis from 2 clinical trials S Nalamachu, R Rauck, D Hassman, V Reddy, J Howell, and G Guillory; International Clinical Research Institute (multicenter), Overland Park, KS
The Journal of Pain
P51
F07 Cancer Pain - Other (302) Epidural ketamine for refractory cancer pain: a case report P Sloan; University of Kentucky, Lexington, KY
Sublingual fentanyl tablet (Abstralâ) is a rapid-onset opioid under evaluation in the United States for the management of breakthrough pain (BTP) in opioid-tolerant patients with cancer. Results of two phase 3, multiple-dose trials demonstrated the efficacy and tolerability of sublingual fentanyl; this pooled analysis evaluated tolerability in patients aged $65 years with cancer-related BTP. Doses of sublingual fentanyl were individually titrated (range, 100-800 mcg) and were administered by placing tablets on the floor of the mouth directly under the tongue, until completely dissolved. Adverse events (AEs) were analyzed by dose group (#200 mcg, 300-400 mcg, and >400 mcg). In total, 270 patients received $1 dose of sublingual fentanyl; 57 (21.1%) were aged $65 years. Incidence of AEs in this age group was 80.7% overall and increased according to dose group (50.0%, 71.4%, and 90.3% in the #200 mcg, 200-300 mcg, and >400 mcg groups), although this may be confounded by the tendency to be on the lower doses for shorter periods of time because of dose titration. The most common AEs in patients aged $65 years included diarrhea (15.8%), nausea (15.8%), and fatigue (14.0%). Incidence of AEs was similar in patients aged 17-64 years (166 [77.9%] experienced $1 AE; the most common AEs were nausea [24.4%], vomiting [12.7%], and fatigue [11.3%]). The majority of AEs in both populations were mild or moderate in severity. No treatment-related AEs at the application site (ie, the sublingual area of the mouth) were reported in either group. These results demonstrate that sublingual fentanyl was generally well tolerated in patients aged $65 years with cancer-related BTP. The safety and tolerability profile was consistent between age groups. Editorial and writing support was provided by Synchrony Medical LLC, funded by ProStrakan Group plc.
Epidural analgesics are indicated for the treatment of cancer pain refractory to traditional analgesics.1 When severe cancer pain is refractory to standard epidural opioid/local anesthetic (LA) combinations, other epidural analgesic compounds are sometimes added in an attempt to provide pain relief. 2 This case report describes a patient with terminal uterine cancer and severe pelvic pain who received inadequate pain relief with epidural opioid/LA analgesics, and in whom epidural ketamine was added for therapy. A 60 year old woman presented with pelvic pain and inoperable uterine cancer. After initial oral opioid analgesics and then a trial of intravenous opioids failed, a trial of T12/L1 lumbar epidural dilaudid/bupivacaine was started. Epidural dosing titrated up to dilaudid 2 mg/hr with bupivacaine 10 mg/hr provided only partial pain relief. The patient was deemed to be in the last days of life and receiving hospice care. On a compassionate basis, epidural ketamine was added to the dilaudid/bupivacaine solution and titrated to 2 mg/hr. The patient had much improved pain relief, however she became confused. The epidural ketamine was decreased in dose, but confusion remained until the ketamine was discontinued. In order to control refractory pain, intravenous midazolam was administered which provided sedation for the patient. After 4 days of treatment the patient died peacefully and without pain. In conclusion, refractory cancer pain may require multiple attempts using different epidural analgesics to achieve effective analgesia. Epidural ketamine provided analgesia for severe cancer pain but with untreatable confusion as a limiting side effect. Research on the safety and dosing of epidural ketamine for refractory cancer pain is needed. (1. Sloan PA, Curr Pain Headache Rep, 2007; 2. Schug SA, CNS Drugs, 2006)
F06 Cancer Pain - Palliative Care
F10 Nerve Blocks
(301) CB2 receptor agonists act as a disease-modifying treatment by attenuating breast cancer-induced bone pain and improving bone health in a murine model of breast cancer metastases
(303) Efficacy of lumbar facet medical branch radiofrequency ablation for chronic low back pain management: a meta-analysis of randomized controlled trials
A Ondoua, K Hanlon, T Largent-Milnes, D Sukhtankar, T King, P Mantyh, and T Vanderah; The University of Arizona, Tucson, AZ
Lumbar facet medial branch (LFMB) radiofrequency ablation (RFA), or neurotomy, is one of the most commonly performed minimally invasive procedures for treatment of chronic low back pain, introduced to clinical practice 35 years ago. Numerous descriptive studies have suggested clinical efficacy of the procedure. However, randomized controlled trials (RCT) revealed conflicting results regarding the efficacy of this procedure. Using a meta-analysis approach, we aim to synthesize the published data from randomized controlled studies and compare the outcomes of RFA with placebo in the management of chronic low back pain associated with lumbar facet arthropathy. We searched the Cochrane Library, OVID, EMBASE, and PUBMED for RCT on the efficacy of LFMB RFA published until September 2010. The fixed effect model meta-analysis of relevant RCTs was performed with the Comprehensive MetaAnalysis V.2 software (Biostat, NJ, USA). Five relevant studies, encompassing 248 patients were included in the analysis: Gallagher et al., 1994, van Kleef et al., 1999, Leclaire et al., 2001, van Wijk et al., 2005, Nath et al., 2008. The trials focused on the efficacy of LFMB RFA on low back pain compared to placebo (sham) procedures. The results showed statistically significant improvement in patients’ pain scores (Log Odds Ratio=0.510; Z=2.060; p=0.039). The difference in outcomes was in favor of RFA in 2-6 months after the procedure. The Classic Fail-Safe N analysis revealed low impact of publication bias on the results of the meta-analysis (Z=2.715; alpha=0.05; p=0.007; number of missing studies that would bring p value to > 0.05 = 5). This first quantitative outcome based analysis of pooled data from the published RCTs suggest that RFA of medial branches in patients with low back pain associated with lumbar facet arthrtopathy is beneficial in pain reduction for 2-6 months.
Metastatic bone cancer, commonly originating from breast cancer, causes severe pain in patients and is primarily treated with strong analgesics such as opiates. Sustained opiates result in severe side effects including analgesic tolerance, somnolence and respiratory depression, and possibly enhanced bone destruction. In contrast, CB2 specific agonists have been shown to reduce bone loss associated with a model of osteoporosis and stimulate cortical thickness. Cannabinoid CB2 agonists also produce analgesic effects for both inflammatory and neuropathic pain. In this study the murine mammary cell line, 66.1, was injected within the intramedullary space of a mouse femur. Here we demonstrate that the systemic administration of the cannabinoid CB2 receptor agonists JWH015 and AM1241 for seven days can assuage spontaneous and evoked pain in a murine model of bone cancer. Effects of CB2 agonists on spontaneous pain and bone destruction were reversed with the concurrent treatment of the CB2 antagonist, SR144528, but not with the CB1 antagonist, SR141716, indicating this effect is CB2 mediated. Treatment with the sustained CB2 agonists, AM1241 or JWH015, improved overall bone integrity. Additionally, JWH015 treatment reduced serum calcium levels and decreased the number of osteoclasts in the metaphyseal region of the femur. JWH015 also decreased the number of 66.1 cells both in vivo and in vitro. Treatment with JWH015 decreased the release of TNFa, both in vivo and in vitro, suggesting a possible mechanism by which this CB2 agonist is attenuating pain and inhibiting proliferation of 66.1 cells. These results suggest a disease modifying treatment for bone cancer pain that would reduce detrimental bone loss, attenuate pain, and avoid side effects seen with current treatments.
D Souzdalnitski and J Cheng; Cleveland Clinic, Cleveland, OH
The Journal of Pain
P51
F07 Cancer Pain - Other (302) Epidural ketamine for refractory cancer pain: a case report P Sloan; University of Kentucky, Lexington, KY
Sublingual fentanyl tablet (Abstralâ) is a rapid-onset opioid under evaluation in the United States for the management of breakthrough pain (BTP) in opioid-tolerant patients with cancer. Results of two phase 3, multiple-dose trials demonstrated the efficacy and tolerability of sublingual fentanyl; this pooled analysis evaluated tolerability in patients aged $65 years with cancer-related BTP. Doses of sublingual fentanyl were individually titrated (range, 100-800 mcg) and were administered by placing tablets on the floor of the mouth directly under the tongue, until completely dissolved. Adverse events (AEs) were analyzed by dose group (#200 mcg, 300-400 mcg, and >400 mcg). In total, 270 patients received $1 dose of sublingual fentanyl; 57 (21.1%) were aged $65 years. Incidence of AEs in this age group was 80.7% overall and increased according to dose group (50.0%, 71.4%, and 90.3% in the #200 mcg, 200-300 mcg, and >400 mcg groups), although this may be confounded by the tendency to be on the lower doses for shorter periods of time because of dose titration. The most common AEs in patients aged $65 years included diarrhea (15.8%), nausea (15.8%), and fatigue (14.0%). Incidence of AEs was similar in patients aged 17-64 years (166 [77.9%] experienced $1 AE; the most common AEs were nausea [24.4%], vomiting [12.7%], and fatigue [11.3%]). The majority of AEs in both populations were mild or moderate in severity. No treatment-related AEs at the application site (ie, the sublingual area of the mouth) were reported in either group. These results demonstrate that sublingual fentanyl was generally well tolerated in patients aged $65 years with cancer-related BTP. The safety and tolerability profile was consistent between age groups. Editorial and writing support was provided by Synchrony Medical LLC, funded by ProStrakan Group plc.
Epidural analgesics are indicated for the treatment of cancer pain refractory to traditional analgesics.1 When severe cancer pain is refractory to standard epidural opioid/local anesthetic (LA) combinations, other epidural analgesic compounds are sometimes added in an attempt to provide pain relief. 2 This case report describes a patient with terminal uterine cancer and severe pelvic pain who received inadequate pain relief with epidural opioid/LA analgesics, and in whom epidural ketamine was added for therapy. A 60 year old woman presented with pelvic pain and inoperable uterine cancer. After initial oral opioid analgesics and then a trial of intravenous opioids failed, a trial of T12/L1 lumbar epidural dilaudid/bupivacaine was started. Epidural dosing titrated up to dilaudid 2 mg/hr with bupivacaine 10 mg/hr provided only partial pain relief. The patient was deemed to be in the last days of life and receiving hospice care. On a compassionate basis, epidural ketamine was added to the dilaudid/bupivacaine solution and titrated to 2 mg/hr. The patient had much improved pain relief, however she became confused. The epidural ketamine was decreased in dose, but confusion remained until the ketamine was discontinued. In order to control refractory pain, intravenous midazolam was administered which provided sedation for the patient. After 4 days of treatment the patient died peacefully and without pain. In conclusion, refractory cancer pain may require multiple attempts using different epidural analgesics to achieve effective analgesia. Epidural ketamine provided analgesia for severe cancer pain but with untreatable confusion as a limiting side effect. Research on the safety and dosing of epidural ketamine for refractory cancer pain is needed. (1. Sloan PA, Curr Pain Headache Rep, 2007; 2. Schug SA, CNS Drugs, 2006)
F06 Cancer Pain - Palliative Care
F10 Nerve Blocks
(301) CB2 receptor agonists act as a disease-modifying treatment by attenuating breast cancer-induced bone pain and improving bone health in a murine model of breast cancer metastases
(303) Efficacy of lumbar facet medical branch radiofrequency ablation for chronic low back pain management: a meta-analysis of randomized controlled trials
A Ondoua, K Hanlon, T Largent-Milnes, D Sukhtankar, T King, P Mantyh, and T Vanderah; The University of Arizona, Tucson, AZ
Lumbar facet medial branch (LFMB) radiofrequency ablation (RFA), or neurotomy, is one of the most commonly performed minimally invasive procedures for treatment of chronic low back pain, introduced to clinical practice 35 years ago. Numerous descriptive studies have suggested clinical efficacy of the procedure. However, randomized controlled trials (RCT) revealed conflicting results regarding the efficacy of this procedure. Using a meta-analysis approach, we aim to synthesize the published data from randomized controlled studies and compare the outcomes of RFA with placebo in the management of chronic low back pain associated with lumbar facet arthropathy. We searched the Cochrane Library, OVID, EMBASE, and PUBMED for RCT on the efficacy of LFMB RFA published until September 2010. The fixed effect model meta-analysis of relevant RCTs was performed with the Comprehensive MetaAnalysis V.2 software (Biostat, NJ, USA). Five relevant studies, encompassing 248 patients were included in the analysis: Gallagher et al., 1994, van Kleef et al., 1999, Leclaire et al., 2001, van Wijk et al., 2005, Nath et al., 2008. The trials focused on the efficacy of LFMB RFA on low back pain compared to placebo (sham) procedures. The results showed statistically significant improvement in patients’ pain scores (Log Odds Ratio=0.510; Z=2.060; p=0.039). The difference in outcomes was in favor of RFA in 2-6 months after the procedure. The Classic Fail-Safe N analysis revealed low impact of publication bias on the results of the meta-analysis (Z=2.715; alpha=0.05; p=0.007; number of missing studies that would bring p value to > 0.05 = 5). This first quantitative outcome based analysis of pooled data from the published RCTs suggest that RFA of medial branches in patients with low back pain associated with lumbar facet arthrtopathy is beneficial in pain reduction for 2-6 months.
Metastatic bone cancer, commonly originating from breast cancer, causes severe pain in patients and is primarily treated with strong analgesics such as opiates. Sustained opiates result in severe side effects including analgesic tolerance, somnolence and respiratory depression, and possibly enhanced bone destruction. In contrast, CB2 specific agonists have been shown to reduce bone loss associated with a model of osteoporosis and stimulate cortical thickness. Cannabinoid CB2 agonists also produce analgesic effects for both inflammatory and neuropathic pain. In this study the murine mammary cell line, 66.1, was injected within the intramedullary space of a mouse femur. Here we demonstrate that the systemic administration of the cannabinoid CB2 receptor agonists JWH015 and AM1241 for seven days can assuage spontaneous and evoked pain in a murine model of bone cancer. Effects of CB2 agonists on spontaneous pain and bone destruction were reversed with the concurrent treatment of the CB2 antagonist, SR144528, but not with the CB1 antagonist, SR141716, indicating this effect is CB2 mediated. Treatment with the sustained CB2 agonists, AM1241 or JWH015, improved overall bone integrity. Additionally, JWH015 treatment reduced serum calcium levels and decreased the number of osteoclasts in the metaphyseal region of the femur. JWH015 also decreased the number of 66.1 cells both in vivo and in vitro. Treatment with JWH015 decreased the release of TNFa, both in vivo and in vitro, suggesting a possible mechanism by which this CB2 agonist is attenuating pain and inhibiting proliferation of 66.1 cells. These results suggest a disease modifying treatment for bone cancer pain that would reduce detrimental bone loss, attenuate pain, and avoid side effects seen with current treatments.
D Souzdalnitski and J Cheng; Cleveland Clinic, Cleveland, OH