Management of pain in elderly patients receiving infusion of zoledronic acid for bone metastasis: a single-institution report (original) (raw)

Zoledronic acid significantly improves pain scores and quality of life in breast cancer patients with bone metastases: a randomised, crossover study of community vs hospital bisphosphonate administration

British journal of cancer, 2005

Patients with bone metastases from breast cancer often experience substantial skeletal complications -- including debilitating bone pain -- which negatively affect quality of life. Zoledronic acid (4 mg) has been demonstrated to reduce significantly the risk of skeletal complications in these patients and is administered via a short, 15-min infusion every 3 weeks, allowing the possibility for home administration. This study compared the efficacy and safety of zoledronic acid administered in the community setting vs the hospital setting in breast cancer patients with > or =1 bone metastasis receiving hormonal therapy. After a lead-in phase of three infusions of 4 mg zoledronic acid in the hospital setting, 101 patients were randomized to receive three open-label infusions in the community or hospital setting, followed by three infusions in the opposite venue (a total of nine infusions). The Brief Pain Inventory (BPI) and the European Organisation for Research and Treatment of Canc...

Combined therapy of Sr89 and zoledronic acid in patients with painful bone metastases

Bone, 2006

Purpose: We evaluated the pain response and daily discomfort in patients with painful bone metastases treated by merging 89 Sr-chloride and zoledronic acid. The results were compared with those of patients who received 89 Sr-chloride or zoledronic acid separately. Methods: 25 patients (12 women; mean age 65 ± 13 years) chronically treated with zoledronic acid underwent bone pain palliation with 150 MBq of 89 Sr-chloride at least 6 months later that bisphoshonate therapy started (group A). 13 patients (6 women; mean age 70 ± 12 years) received 89 Srchloride alone (group B) and 11 patients (5 women; mean age 69 ± 12 years) were chronically treated and continued to receive only zoledronic acid therapy (group C), both constituted the control groups. Patients kept a daily pain diary assessing both their discomfort and the pain of specific sites by using a visual analog scale (VAS), rating from 0 (no discomfort-no pain) to 10 (worst discomfort-pain). These diaries were reviewed weekly for 2 months and three different physicians rated the pain response on a scale of −2 (considerable deterioration) to +2 (considerable improvement). Results: Baseline characteristics were similar in the three groups. The reduction of total discomfort and of bone pain in the group A was significantly greater as compared to group B (P b 0.01) and group C (P b 0.01). During the monitored period, a significant improvement of clinical conditions was observed in the group A, varying the rate from −1 to 1 as compared to both groups B and C in which the rate changed from −1 to 0. Conclusion: Our findings indicate that combined therapy of 89 Sr-chloride and zoledronic acid in patients with painful bone metastases is more effective in treating pain and improving clinical conditions than 89 Sr-chloride or zoledronic acid used separately.

Management of Painful Bone Metastases: The Interaction between Radiation Therapy and Zoledronate

Journal of Cancer Therapy, 2011

Background: Advanced cancers frequently metastasize to bone, and the presence of bone metastases is the most common cause of cancer-related pain. Pain management requires a multidisciplinary approach that involves the use of analgesics, bisphosphonates, radiotherapy, chemotherapy, surgery. The aim of our study was to evaluate the enhancement of radiotherapy on painful bone metastases in patients treated also with bisphosphonates. Materials and Methods: We analyzed the differences in benefit on pain and on quality of life comparing two groups of treatment. The first group comprised 104 patients treated with Radiotherapy (RT), the second one included 50 patients treated with radiotherapy associated to zoledronic acid (RT + Z). All patients completed before, during and after treatment, a questionnaire that rated the grade of pain, the pharmacological type of analgesic therapy and patient's performance status. For each patient a total score was calculated, from a minimum value of 0% to a maximum of 20%, then expressed as a percentage. Patients were classified as responder if at the follow-up reported a reduction of over 20% of the initial score, no -change if there was a reduction of between 0% and 20%, progression if there was an increasing of the score. Results: In the group RT + Z we found fewer patients that started radiation therapy with severe pain (16% vs 32%), no patient had pain of grade 10, and a higher proportion of asymptomatic patients (12% vs 4%) was observed. In the RT alone group a higher percentage of patients started treatment assuming strong opioid more than once a day (26% vs 24%) and a reduction in number of these patients was about 14% compared with the reduction of 23.6% observed in the group RT + Z. Furthermore an increased total score was calculated only in the 6% of patient belonged to group RT alone. Finally, in the group RT + Z responder patients are 52%, compared to 36% of the RT group, non-responder were 36% versus 60% in the RT. The risk of adverse events (Pz) in the RT + Z was Pz = 0.36, with an odds (Oz) equal to 0.56, while the risk of adverse events (Pc) in the RT group was Pc = 0.60 with an odds (O C ) of 1.5. The odds ratio was OR = 0.37, showing a value in favor of treatment RT + Z. Conclusions In our retrospective observational study it is relevant a clear potentiation of benefit effects related to palliative radiation therapy in patients receiving also bisphosphonate therapy, so obtaining a better control over pain, a decreased need for pain relief and consequently an improved quality of life.

Effect of bisphosphonates on pain and quality of life in patients with bone metastases

Nature Reviews Clinical Oncology, 2009

Bone is the most common organ for tumor metastasis, especially in patients with cancers of the breast or prostate. Bone metastases disrupt skeletal metabolism and result in considerable skeletal morbidity, including intractable, chronic bone pain, hypercalcemia of malignancy, pathologic fracture and spinal-cord compression. In addition to the chronic pain caused by bone metastases, skeletal-related events (SREs) such as pathologic fractures and spinal-cord compression can result in acute increases in pain. These effects can severely impair mobility and contribute to a general decrease in quality of life. Palliative options to treat bone metastases include radiotherapy, analgesics, surgery and bisphosphonates. These drugs bind to the surface of the bone and impair osteoclast-mediated bone resorption, and reduce the tumor-associated osteolysis that is initiated by the development of skeletal metastases. In addition to preventing SREs, bisphosphonates can palliate bone pain caused by a variety of solid tumors. This Review summarizes the clinical trial data of bisphosphonates for the prevention of SREs and the palliation of bone pain. Among these agents, nitrogen-containing bisphosphonates are recognized as the most effective, and zoledronic acid has demonstrated the broadest clinical utility.

Zoledronic acid in the management of metastatic bone disease

Expert Opinion on Biological Therapy, 2006

Many patients with advanced cancer experience decreased bone strength due to metastatic foci, underlying osteoporosis and/or cancer treatment induced bone loss. The clinical consequences of metastatic disease involving the skeleton are widespread. This review focuses on the effi cacy, pharmacology, and safety when using intravenous biphosphonate such a zoledronic acid for cancer bone metastases. Zoledronic acid is the gold standard for the medical management of metastatic bone disease. The indications for treatment include prevention of skeletal relevant events (SRE), osteoporotic complications, and palliation of bone pain, among others. Zoledronic acid is the only bisphosphonate effective in decreasing SREs associated with bone metastases from advanced renal cell carcinoma and prostate cancer. Regarding prostate cancer, zoledronic acid effectively prevents both bone loss in patients with locally advanced disease receiving androgen deprivation therapy and SREs in men with hormone-refractory or hormonesensitive metastatic disease. Zoledronic acid has an acceptable safety profi le and tolerability, and has been effective at signifi cantly decreasing the incidence, delaying the onset, and reducing the overall risk of experiencing an SRE compared to placebo. It is the only bisphosphonate currently approved for the prevention and treatment of skeletal complications in patients with bone metastases due to all solid tumors.

Optimal Timing of Bisphosphonate Administration in Combination with Samarium-153 Oxabifore in the Treatment of Painful Metastatic Bone Disease

World Journal of Nuclear Medicine, 2013

While bisphosphonates are indicated for prevention of skeletal-related events, radionuclide therapy is widely used for treatment of painful bone metastases. Combined radionuclide therapy with bisphosphonates has demonstrated improved effectiveness in achieving bone pain palliation in comparison to mono therapy with radionuclides or bisphosphonates alone. However, there are conflicting reports as to whether bisphosphonates adversely influence skeletal uptake of the bone-seeking radiotracers used for therapy. Recent studies analyzing influence of Zoledronic acid on total bone uptake of Samarium-153 EDTMP (Sm-153 EDTMP) by measuring cumulative urinary activity of Sm-153 on baseline study, as well as in combination with bisphosphonates (administrated 48 hours prior to Sm-153) did not provide any statistically significant difference in urinary excretion of Sm-153 between the two groups. It may be noted that the exact temporal sequence of bisphosphonate administration vis a vis radionuclide therapy has not yet been studied. One of the side effects of bisphosphonates is transient flare effect on bone pain. Radionuclide therapy may also have similar side effect. Keeping in view the above the current study was designed with the main objective of determining the exact timing of bisphosphonate administration in patients receiving combined therapy so as to achieve optimal efficacy of bone pain palliation. Ninety-three patients suffering from metastatic bone pain who received combination therapy with Sm-153 oxabifore (an analog of Sm-153 EDTMP) and Zoledronic acid were divided into three groups according to the timing of Zoledronic acid administration: Group I: 39 patients who received Zoledronic acid 7 or more days prior to Sm-153 oxabifore treatment; Group II: 32 patients who received Zoledronic acid 48-72 hours prior to Sm-153 oxabifore treatment and Group III: 22 patients who received Zoledronic acid 7 days after Sm-153 oxabifore treatment. Sm-153 oxabifore was administered to all patients at the standard bone palliation dose of 37 MBq/kg body weight. All patients received Zoledronic acid before and after treatment in standard dosage of 4 mg every 28 days. WB bone scan, CT, and MRI were performed before treatment in all patients to exclude cord compression and vertebral fractures. Pain scores and quality of life (QOL) measurements were recorded meticulously in all patients. In groups I, II, and III, pain relief occurred in 10.4 ± 3.1 (Range = 5-15); 3.1 ± 1.1 (Range = 1-5) and 22 ± 5.1 (Range = 15-35) days, respectively, following radionuclide therapy. There was statistically significant difference between pain score in all groups before and after treatment as well as statistically significant difference in time to pain relief onset between Group II and other groups of patients (P < 0.0001). Based on our results we concluded that administration of Zoledronic acid 48-72 hours prior to Sm-153 oxabifore treatment helps in achieving better pain relief, as well as at the shortest time interval from the start of therapy.

Long-term safety of monthly zoledronic acid therapy beyond 1 year in patients with advanced cancer involving bone (LoTESS): A multicentre prospective phase 4 study

European Journal of Cancer Care, 2017

Malignant bone disease can cause significant morbidity. Monthly zoledronic acid (ZOL) reduces skeletal complications; however, limited data are available regarding longterm safety. We aimed to assess efficacy and safety of ZOL beyond 1 year of treatment. We prospectively evaluated 73 patients; breast cancer (n = 29), castrate-resistant prostate cancer (n = 13), multiple myeloma (n = 31) from 2006 to 2008 in 19 cancer centres. All patients were diagnosed with bone disease and had completed 1-2 years of monthly ZOL (4 mg) and received a further 1-2 years of therapy following contemporary guidelines for managing risks of osteonecrosis of the jaw (ONJ) and renal toxicity. Overall rates of skeletal-related events (SREs), renal impairment and ONJ were assessed. Over the additional 1 year of treatment, only 5.5% (n = 4) of patients developed a new SRE. The overall Kaplan-Meier estimate for SRE incidence after 48 weeks on study was 6.75% (95 CI: 2.5-17.3). Although 51% of patients reported serious adverse events, only two cases were suspected as ZOL related. No patients had confirmed ONJ. The observed incidence of new renal impairment was 11% (none due to ZOL). Our study confirms the benefit over risk of continuing monthly ZOL for at least 2 years in patients with advanced cancer involving bone. K E Y W O R D S bone metastasis, long-term safety, osteonecrosis of the jaw, renal impairment, zoledronic acid 1 | INTRODUCTION Bone disease associated with different types of cancer can cause a significant burden on patients, often resulting in disability that compromises cancer treatment (Berenson, 2005; Hillner et al., 2003; Morgan et al., 2012). It remains a major challenge for clinicians to control malignant disease, while at the same time offering an effective supportive treatment to reverse, prevent or at least slow the progression of the bone disease or skeletal events associated with different