Treatment Of Painful Bone Metastases Research Articles

Treatment of painful bone metastases

Bone metastases are the most common cause of cancer-related pain. Radiotherapy is a safe and effective therapy and is well established for such a situation. A fractionation regimen with a short overall treatment time (< or =1 week) would be preferred if it was as effective as longer courses (2-4 weeks). Randomized clinical trials and meta-analyses have demonstrated that single-fraction radiotherapy with 1 x 8 Gy is as effective for pain relief as multi-fraction regimens such as 5 x 4 Gy in 1 week or 10 x 3 Gy in 2 weeks. Re-irradiation for recurrent pain in the irradiated region is required more often after single-fraction radiotherapy than multi-fraction radiotherapy; however, re-irradiation following single-fraction radiotherapy is safe and effective. Thus, 1 x 8 Gy is considered the standard regimen for uncomplicated painful bone metastases without pathological fractures or spinal cord compression. Multi-fraction radiotherapy results in significantly better remineralization of the osteolytic bone than single-fraction radiotherapy. Remineralization is important for preventing or treating pathological fractures. Multi-fraction long-course radiotherapy results in fewer recurrences of spinal-cord compression within the irradiated spinal region. Thus, long-course multi-fraction radiotherapy should be reserved for patients with a relatively favorable survival prognosis.

Efficacy of radiotherapy for painful bone metastases during the last 12 weeks of life

Radiotherapy is an effective treatment for painful bone metastases. Whether this applies also in patients with limited survival remains to be investigated. This study analyzed the effect of radiotherapy for painful bone metastases in patients with a survival < or =12 weeks. In the Dutch Bone Metastasis Study, 1157 patients with painful bone metastases were randomized to single fraction (1 x 8 grays [Gy]) or multiple fraction (6 x 4 Gy) radiotherapy. Patients who died within 12 weeks after randomization were included in this analysis. Patients were classified as responders or nonresponders, based on their pain response to radiotherapy. This response was calculated considering changes in pain intensity (measured with an 11-point numeric rating scale) and analgesic usage. Cox proportional hazards models were used to analyze pain response and survival. Two hundred seventy-4 patients were included in this analysis. At randomization, the mean pain intensity score (+/-standard deviation) was 7 (+/-2). The proportion showing a pain response did not differ between the single fraction and multiple fraction groups. Toward death, pain intensity score decreased to 5 (+/-3) in responders (45%), whereas in nonresponders (55%) no change was observed. Despite the benefit in responders, in 60% of all patients pain intensity remained 5 after randomization. Pain responded in about half of the patients who survived < or =12 weeks after randomization into the Dutch Bone Metastasis Study. When considering radiotherapy, single fraction should be preferred. Additional palliative measures remain essential for adequate pain control.

Treatment of Painful Bone Metastases in Hormone-Refractory Prostate Cancer with Zoledronic Acid and Samarium-153-Ethylenediaminetetramethylphosphonic Acid Combined

Abstract Bone-seeking radiopharmaceuticals and bisphosphonates may be indicated in patients with cancer with painful osseous metastases to palliate pain symptoms or to prevent skeletal-related events. Both pharmaceuticals may have an additive or even synergistic palliative effect. The combined use of bone-seeking radiopharmaceuticals and bisphosphonates is, however, controversial because of assumed competition between both phosphonate-compounds at the bone level. We report a case of hormone-refractory prostate cancer (HRPC) with multiple painful osseous metastases. The patient was treated with samarium-153-ethylenediaminetetramethylphosphonic acid ((153)Sm-EDTMP; Quadramet, CIS bio International, Saclay, France) in combination with zoledronic acid (Zometa, Novartis, Stein, Switzerland). He was treated for 6 months with 4 weekly intervals of zoledronic acid in combination with 3 monthly intervals of (153)Sm-EDTMP. No negative interaction was found, toxicity was low, and efficacy high. He experienced a total relief of pain, a significant decrease of prostate-specific antigen (PSA) and, surprisingly, a significant decrease of tumor burden.

Optimal treatment of painful bone metastases with Samarium EDTMP in a haemodialysis patient: effectiveness and safety of internal radiotherapy

One of the current therapeutic approaches in the treatment of osteoblastic bone metastases uses the affinity of Samarium ((153)Sm) ethylene-diamine-tetramethylene phosphonic acid (EDTMP) for bone areas of bone turnover. As Samarium EDTMP is a beta-emitter, the radiotherapy contributes to osteoblastic bone lesion control over time. To date, the safety and effectiveness of Samarium therapy have not been established in patients with renal impairment. In this first report, we describe our experience of use of Samarium EDTMP in conjunction with biphosphonates in a haemodialysis patient for treatment of painful bone metastasis. Encouraging results were obtained in achieving pain control. The use of this radioisotope could be more widely applied to treat haemodialysis patients.

Development of [90Y]DOTA-conjugated bisphosphonate for treatment of painful bone metastases

Based on the concept of bifunctional radiopharmaceuticals, we have previously developed (186)Re-complex-conjugated bisphosphonate analogs for palliation of painful bone metastases and have demonstrated the utility of these compounds. By applying a similar concept, we hypothesized that a bone-specific directed (90)Y-labeled radiopharmaceutical could be developed. In this study, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was chosen as the chelating site, and DOTA was conjugated with 4-amino-1-hydroxybutylidene-1,1-bisphosphonate. [(90)Y]DOTA-complex-conjugated bisphosphonate ([(90)Y]DOTA-HBP) was prepared by coordination with (90)Y, and its biodistribution was studied in comparison to [(90)Y]citrate. In biodistribution experiments, [(90)Y]DOTA-HBP and [(90)Y]citrate rapidly accumulated and resided in the bone. Although [(90)Y]citrate showed a higher level of accumulation in the bone than [(90)Y]DOTA-HBP, the clearances of [(90)Y]DOTA-HBP from the blood and from almost all soft tissues were much faster than those of [(90)Y]citrate. As a result, the estimated absorbed dose ratios of soft tissues to osteogenic cells (target organ) of [(90)Y]DOTA-HBP were lower than those of [(90)Y]citrate. [(90)Y]DOTA-HBP showed superior biodistribution characteristics as a bone-seeking agent and led to a decrease in the level of unnecessary radiation compared to [(90)Y]citrate. Since the DOTA ligand forms a stable complex not only with (90)Y but also with lutetium ((177)Lu), indium ((111)In), gallium ((67/68)Ga), gadolinium (Gd) and so on, complexes of DOTA-conjugated bisphosphonate with various metals could be useful as agents for palliation of metastatic bone pain, bone scintigraphy and magnetic resonance imaging.

Radiotherapy in palliative treatment of painful bone metastases

Radiotherapy in palliative treatment of painful bone metastasesBackground. Pain caused by bone metastases is the most common symptom requiring the treatment in cancer patients. Bone metastases often present as the first evidence of disseminated disease, the most common primary sites being breast, prostate, and lung. Important in palliative treatment is to reach a maximal effect with the minimal treatment. The aim of palliation for cancer patients is to increase the quality of their remaining life.Conclusions. The management of bone pain includes analgesics, local treatment (radiation, surgery) and systemic treatment (hormones, chemotherapy, radioisotopes and agents such as bisphosphonates). The treatment of bone cancer pain often requires a multidisciplinary approach. Radiotherapy remains the most important palliative treatment for localized bone pain. The treatment duration can generally be reduced to a single treatment with excellent and long-lasting palliative analgesic responses. The treatment should be individualized according to the patient's clinical condition and life expectancy.

Usefulness of competitive inhibitors of protein binding for improving the pharmacokinetics of 186Re-MAG3-conjugated bisphosphonate (186Re-MAG3-HBP), an agent for treatment of painful bone metastases

We have developed a (186)Re-mercaptoacetylglycylglycylglycine complex-conjugated bisphosphonate ((186)Re-MAG3-HBP) for the treatment of painful bone metastases. We assumed competitive inhibitors of protein binding to be useful for procuring a favorable biodistribution of (186)Re-MAG3-HBP for the palliation of bone pain because it has been reported that the concurrent administration of (99m)Tc-MAG3 and drugs with high affinity for serum protein produced competitive displacement at specific binding sites and enhanced total clearance and tissue distribution. The displacement effects of several protein-binding inhibitors on the protein binding of (186)Re-MAG3-HBP were investigated. Biodistribution experiments were performed by intravenously administering (186)Re-MAG3-HBP into rats with ceftriaxone as a competitive protein-binding inhibitor or saline. The protein binding of (186)Re-MAG3-HBP in rat serum, human serum, and a human serum albumin solution was significantly decreased by the addition of ceftriaxone, which has high affinity for binding site I on serum albumin. In the biodistribution experiments, pretreatment with ceftriaxone enhanced the clearance of the radioactivity of (186)Re-MAG3-HBP in blood and nontarget tissues but had no effect on accumulation in bone. The findings suggested that the use of protein-binding competitive inhibitors would be effective in improving the pharmacokinetics of radiopharmaceuticals with high affinity for serum protein.

153Sm: its use in multiple myeloma and report of a clinical experience

Background: In the past years the bone seeking radiopharmaceutical samarium lexidronam (153Sm-EDTMP) has been increasingly used alone or in conjunction with chemotherapy and/or bisphosphonates for the treatment of painful bone metastasis. Objective: Its use has been explored in different solid tumours. In this report we explore its interesting characteristics and describe our experience in multiple myeloma (MM). Methods: 153Sm-EDTMP has an affinity for bone and concentrates in areas of bone turnover. It decays as a therapeutic β-emission and at the same time as γ-photon that can be used for tracking its concentration with bone scan imaging. Ten patients with symptomatic MM were treated to achieve pain control. Results: Encouraging results were obtained in MM patients. The use of this radioisotope could be largely improved.

Palliative Treatment of Painful Bone Metastases with MR Imaging–guided Focused Ultrasound

To evaluate the safety and initial efficacy of magnetic resonance (MR) imaging-guided focused ultrasound for the palliation of pain caused by bone metastases in patients in whom standard available treatments had been ineffective or not feasible. Informed consent was obtained in 11 patients (seven women, four men; average age, 58.6 years) with pain related to non-weight-bearing bone metastases who were subsequently treated with MR imaging-guided focused ultrasound in this research and ethics board-approved study. Efficacy was evaluated by changes in visual analog scale (VAS) scores, in pain medication usage, and in quality of life. Safety of the device was evaluated by recording incidence and severity of treatment-related adverse events up to 3 months after treatment at physical examination and follow-up imaging. Follow-up imaging included contrast material-enhanced MR imaging and unenhanced computed tomography (CT) 1 month after treatment and contrast-enhanced MR imaging 3 months after treatment. Imaging studies were assessed for changes in tumor imaging characteristics and any adverse events associated with MR imaging-guided focused ultrasound treatment. Twelve lesions were treated in 11 patients. All patients reported progressive decrease in pain in treated regions and reduction in pain medication usage during the 3-month follow-up period. VAS scores averaged 6.0 before treatment and decreased to 0.5 at 3 months (decrease in pain scores, 92%; P < .01). No adverse events were recorded at physical examination or follow-up imaging. The majority of patients with osteolytic metastases had varying degrees of necrosis of the enhancing medullary component of the metastasis at follow-up enhanced MR imaging. Five patients had increased bone density at the site of treated osteolytic metastases at follow-up unenhanced CT at 3 months after MR imaging-guided focused ultrasound. MR imaging-guided focused ultrasound is a noninvasive technique that allows palliative treatment of bone metastases with little or no morbidity.

Radiofrequency ablation of osseous metastases for the palliation of pain

A number of different methods have been proposed for pain relief in cancer patients with bone metastases, each with different indications, contraindications and complications (systemic analgesics, bisphosphonates, antitumor chemotherapy, radiotherapy, systemic radio-isotopes, local surgery and vertebroplasty). The ideal treatment has to be fast, safe, effective and tolerable for the patient. CT-guided radiofrequency (RF) ablation may fulfill these criteria. Our experience in the treatment of 30 patients (34 lesions) with painful bone metastases using RF ablation was assessed. There was a significant decrease in the mean past-24-h Brief Pain Inventory (BPI) score for worst pain, for average pain and for pain interference during daily life (4.7, 4.8 and 5.3 units respectively) 4 and 8 weeks after treatment. There was a marked decrease (3 out of 30 patients 4 and 8 weeks after treatment) in the use of analgesics. CT-guided RF ablation appears to be effective for treatment of painful bone metastases.

Palliative treatment of painful bone metastases: Does fractionation matter?

Metastatic bone pain is acommonly encountered clinical condition seen in oncology clinical practice. About 50% of all cancer patients develop metastases in their lifetime and half of them develop skeletal metastases. Despite its importance, no specific therapeutic strategy, to prevent or treat this complication of cancer has been demonstrated. This study comparing two radiotherapy regimens was conducted at a cancer center in New Delhi, India. Patients with confirmed bone metastases were randomized into two treatment arms, Group A (single fraction) and Group B (multiple fractions). Patients were followed up for 12 weeks. Pain relief was the primary endpoint of the treatment. Other parameters were improvement in analgesic score, performance status, and acute side effects like nausea, vomiting, tiredness, and lassitude. Fifty patients were evaluated at the end of the study. Overall response rate was seen in 86% of cases, whereas complete response was seen in 36% of cases. The two treatment regimens were found to be comparable with respect to other endpoints. Hence, a single fraction treatment, which is more convenient and cost effective, is a more logical approach in the Indian scenario in selected cases.

Combined use of zoledronic acid and 153Sm-EDTMP in hormone-refractory prostate cancer patients with bone metastases

Purpose153Sm-ethylenediaminetetramethylenephosphonic acid (EDTMP; Quadramet®) is indicated for the treatment of painful bone metastases, whereas zoledronic acid (Zometa®) is indicated for the prevention of skeletal complications. Because of the different therapeutic effects, combining the treatments may be beneficial. Both, however, accumulate in areas with increased osteoblastic activity. Possible drug interactions were investigated.MethodsPatients with hormone-refractory prostate cancer were treated with 18.5 MBq/kg 153Sm-EDTMP in weeks 1 and 3 and with 37 MBq/kg in week 15. Treatment with 4 mg zoledronic acid began in week 3 and continued every 4 weeks through week 23. In weeks 3 and 15, zoledronic acid was administered 2 days before 153Sm-EDTMP treatment. Urine was collected 48 h after injection of 153Sm-EDTMP, and whole-body images were obtained 6, 24 and 48 h post-injection. The effect of zoledronic acid on total bone uptake of 153Sm-EDTMP was measured indirectly by the cumulative activity excreted in the urine in weeks 1, 3 and 15. Biodistribution, safety, tolerability and effect on prostate-specific antigen level were also studied.ResultsThe urinary excretion in week 3 divided by the urinary excretion in week 1 (baseline) times 100% was mean 98.4 ± 11.6% (median 96.2%). From week 1 to 15, after four zoledronic acid treatments, the mean ratio was 101.9 ± 10.7% (median 101.8%). Bioequivalence could be concluded by using a two-sample t test for both per-protocol (n = 13) and full-analysis sets (n = 18). Toxicity was comparable to of monotherapy with 153Sm-EDTMP.ConclusionZoledronic acid treatment does not influence 153Sm-EDTMP skeletal uptake. Combined treatment is feasible and safe.

Palliative Radiotherapy Trials for Bone Metastases: A Systematic Review

The objective is to update previous meta-analyses with a systematic review of randomized palliative radiotherapy (RT) trials comparing single fractions (SFs) versus multiple fractions (MFs). The analysis includes all published reports from randomized trials comparing SF or MF schedules for the treatment of painful bone metastases with localized RT. A systematic review was performed using the random-effects model with Review Manager version 4.1 (Cochrane Collaboration, Oxford, UK). The odds ratio and 95% CI were calculated for each trial and presented in a forest plot. A total of 16 randomized trials from 1986 onward were identified. For intention-to-treat patients, the overall response (OR) rates for pain were similar for SF at 1,468 (58%) of 2,513 patients and MF RT at 1,466 (59%) of 2,487 patients. The complete response (CR) rates for pain were 23% (545 of 2,375 patients) for SF and 24% (558 of 2,351 patients) for MF RT. No significant differences were found in response rates. Trends showing an increased risk for SF RT arm patients in terms of pathological fractures and spinal cord compressions were observed, but neither were statistically significant (P = .75 and P = .13, respectively). The likelihood of re-treatment was 2.5-fold higher (95% CI, 1.76 to 3.56) in SF RT arm patients (P < .00001). Repeated analysis of these end points, excluding dropout patients, did not alter the conclusions. Generally, no significant differences with respect to acute toxicities were observed between the arms. No significant differences in the arms were observed for overall and CR rates in both intention-to-treat and assessable patients. However, a significantly higher re-treatment rate with SFs was evident.

Palliative Radiation Therapy of Symptomatic Recurrent Bladder Cancer

Palliative radiation therapy (RT) is an established tool in the management of symptoms caused by malignancies. RT is effective at palliating both locally advanced and metastatic cancer, including related symptoms of pain, bleeding, or obstruction. Most data on palliative RT is in regard to its use in the treatment of painful bone metastases. There are also data that support RT palliation for locally advanced or recurrent rectal, prostate, and gynecological cancers. With regard to bladder cancer there is some evidence of the benefit of palliative RT for the control of urinary symptoms and hematuria; however, there is little evidence for the use of palliative RT for pain associated with locally recurrent bladder cancer. We report a case of locally advanced recurrent bladder cancer which was refractory to medical pain management, and was found to be highly responsive to palliative RT. An 80-year-old woman with recurrent bladder cancer and intractable pelvic pain refractory to oral and transdermal pain medications, received palliative pelvic RT to a dose of 50 Gy (5000 cGy) in 25 fractions with complete resolution of pain. The patient was originally found to have dysuria, frequency, and hematuria, secondary to an invasive high grade transitional cell carcinoma of the bladder with an adenocarcinoma component, AJCC pT2b N1 M0 Stage IV, for which she underwent a radical cystectomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, partial vaginectomy, and ileal conduit reconstruction. After undergoing 4 cycles of adjuvant chemotherapy, the patient did well for 5 months with no evidence of symptomatic, clinical, or radiographic recurrence of disease. Repeat staging CT of the abdomen and pelvis confirmed tumor recurrence in the left pelvis. The patient was treated with another course of chemotherapy and pain was managed with relatively low doses of opioid medication (25mcg transdermal fentanyl patch, and oxycodone 5mg bid). However at the fourth month, there was rapid escalation of severe pain with the patient becoming bed bound due to pain with an associated decrease in ambulation and anorexia. Ultimately a pain medication regimen of 200mcg transdermal fentanyl patch q2 days, oxycontin 20mg bid, oxycodone 5 - 10mg q 4 hours, ibuprofen 400mg q 8 hours, and gabapentin 600mg TID was not effective in controlling pain. The patient was then referred to Radiation Oncology 6 months after the pain initially began for evaluation. She received a total of 5000cGy over 25 fractions to a small pelvis field over 5 weeks and reported complete pain resolution. She was able to decrease pain medications, increase overall activity, and gain significant improvement in sleep quality and appetite even early on in the course of her radiation therapy. Palliative radiation therapy has been well studied in the setting of bone metastases and treatment of hematuria for locally advanced bladder cancer. There is little data that we are aware of on the use of RT for pain control with patients that have recurrent, locally advanced bladder cancer. We have presented a case in which an excellent outcome in pain control was seen for a patient with medically unmanageable pain. RT is an excellent option for pain management in recurrent bladder cancer and should be offered to patients whose pain is not otherwise optimally controlled. Palliative RT is an important component in the multimodality approach to cancer pain management and optimization of quality of life.

Prospective randomised multicenter trial on single fraction radiotherapy (8 Gy × 1) versus multiple fractions (3 Gy × 10) in the treatment of painful bone metastases

Prospective randomised multicenter trial on single fraction radiotherapy (8 Gy × 1) versus multiple fractions (3 Gy × 10) in the treatment of painful bone metastases

Safety and efficacy of repeat administration of samarium Sm‐153 lexidronam to patients with metastatic bone pain

Samarium Sm 153 lexidronam (Sm-153) is an effective and well-tolerated treatment for painful bone metastases. The purpose of the analysis was to assess the safety and efficacy of repeated doses of Sm-153 in patients with metastatic bone pain. Data were collected prospectively for 202 patients administered 1.0 mCi/kg of Sm-153. Particular emphasis was placed on analysis of data from 55 patients receiving > or = 2 doses. Pain scores, adverse events, and hematologic parameters were assessed after each dose. Mild, transient suppression of platelets and white blood cell counts was the most common adverse event after treatment. Nadirs were approximately half of baseline at 4 weeks after dosing with recovery by Week 8 in 90% of patients. Temporary grade 3 thrombocytopenia occurred in 11%, 12%, and 17% of patients after the first, second, and third drug administration, respectively. Grade 3 leukopenia occurred in less than 7% of patients independent of the number of administrations. Significant decreases in pain scores (P < .001) were observed at Week 4 after each of the first 3 doses and maintained at Week 8 after the first 2 doses (P < .003) but not the third. Decreases in pain scores were observed in 70%, 63%, and 80% of patients, respectively, at Week 4 after the first 3 administrations. Repeated dosing of 1.0 mCi/kg of Sm-153 was both safe and effective and is a reasonable treatment option in patients whose bone pain responds and then recurs after an initial dose provided that adequate hematologic function is present at the time of drug administration.

Clinical Role of Sm-153 EDTMP in the Treatment of Painful Bone Metastatic Disease

Sm-153 EDTMP is an effective treatment of painful bone metastases from different neoplasms. However, there are few studies describing clinical experience with this therapeutic modality. The aim of this clinical study was to evaluate the efficacy of Sm-153 EDTMP in a group of patients with skeletal metastases and poor pain control with conventional therapies. Sixty-four patients with painful bone metastases treated with Sm-153 EDTMP were retrospectively evaluated. Nine patients were treated twice. The most common primaries were breast in 28 cases (44%) and prostate in 27 (41%). Treatment efficacy was assessed by a visual analog scale, analgesic consumption, and performance status before and after treatment. Response was graded as complete, moderate, or minor. Toxicity evaluation included analytic parameters (blood counts, renal function) and clinical follow up. Efficacy and toxicity were evaluated separately for each dose (total doses: 73), and complete follow up was only possible in 62 of 73 administrations. The response rate was 85% (21% complete, 40% moderate, and 24% minor). Onset of improvement took place a median of 7 days after Sm-153 EDTMP administration, and pain relief persisted for a mean of 3 months. No relevant toxicity was found in the early phase. Myelotoxicity appeared in 29% of the administrations and was mild in most cases (there was one case of grade 4 leukopenia). Sm-153 EDTMP is a good therapeutic option for patients with painful bone metastases. It is an effective treatment of pain relief without major secondary effects.

Prospective randomised multicenter trial on single fraction radiotherapy (8 Gy×1) versus multiple fractions (3 Gy×10) in the treatment of painful bone metastases

Background and purpose To investigate whether single-fraction radiotherapy is equal to multiple fractions in the treatment of painful metastases. Patients and methods The study planned to recruit 1000 patients with painful bone metastases from four Norwegian and six Swedish hospitals. Patients were randomized to single-fraction (8 Gy×1) or multiple-fraction (3 Gy×10) radiotherapy. The primary endpoint of the study was pain relief, with fatigue and global quality of life as the secondary endpoints. Results The data monitoring committee recommended closure of the study after 376 patients had been recruited because interim analyses indicated that, as in two other recently published trials, the treatment groups had similar outcomes. Both groups experienced similar pain relief within the first 4 months, and this was maintained throughout the 28-week follow-up. No differences were found for fatigue and global quality of life. Survival was similar in both groups, with median survival of 8–9 months. Conclusions Single-fraction 8 Gy and multiple-fraction radiotherapy provide similar pain benefit. These results, confirming those of other studies, indicate that single-fraction 8 Gy should be standard management policy for these patients.

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.

Neurotoxicity from Chronic Opioid Therapy After Successful Palliative Treatment for Painful Bone Metastases

A 64-year-old man with severe bone pain secondary to pathological fracture of a vertebra required large doses of morphine to obtain pain relief. After receiving effective palliative anti-tumor treatment, he developed chronic opioid neurotoxicity. We postulate that the gradual reduction in pain over a period of time precipitated the development of toxicity that presented as cognitive failure. Delayed opioid toxicity is a potential consequence of effective disease-modifying therapies that needs to be recognized and treated appropriately when it occurs. The increasing use of community-based palliative care after hospitalization means that the community practitioner also needs to be aware of the development of chronic opioid toxicity at home. Optimal timing for going back down the ladder of opioid doses, after reduction of the noxious stimulus, requires clinicians to recognize different types of symptoms and signs and to consider the effect of other treatments and time on the noxious stimulus. A suggested protocol warrants consideration as a means of improving clinical practice; however, it requires prospective evaluation in the clinical setting.