Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bisphosphonates (BPs) are potent inhibitors of osteoclast-mediated bone resorption, and it is well accepted that tumor cells in bone, especially breast cancer and myeloma cells, can stimulate osteoclast formation and activity leading to the release of growth factors or cytokines, which will further stimulate cancer cells' growth and their secretion of osteolytic factors. BPs are now the standard treatment for cancer hypercalcemia, for which a dose of 90 mg of pamidronate or 1500 mg of clodronate is recommended; the former compound is more potent and has a longer lasting effect. Repeated pamidronate infusions exert clinically relevant analgesic effects in more than half of patients with metastatic bone pain. Recent data suggest that non-responding patients should perhaps be treated with higher doses. The optimal dose actually remains to be defined, especially as it is thought that it is probably a function of the disease stage. Regular pamidronate infusions can also achieve a partial objective response according to conventional UICC criteria and they can almost double the objective response rate to chemotherapy. Lifelong administration of oral clodronate to patients with breast cancer metastatic to bone reduces the frequency of morbid skeletal events by more than one-fourth. Two double-blind randomized placebo-controlled trials comparing monthly 90 mg pamidronate infusions to placebo infusions for 1-2 years in addition to hormone or chemotherapy in patients with at least one lytic bone metastasis have shown that the mean skeletal morbidity rate could be reduced by 30-40%. The results obtained with intravenous BPs are generally viewed as better than those obtained with oral clodronate. However, preference can be given to the oral route when BPs are started early in the process of metastatic bone disease in a patient receiving hormone therapy. According to the recently published ASCO guidelines, pamidronate 90 mg i.v. delivered over 2 h every 3-4 weeks can be recommended in patients with metastatic breast cancer who have imaging evidence of lytic destruction of bone and who are concurrently receiving systemic therapy with hormonal therapy or chemotherapy. Furthermore, the ASCO Panel considered it "reasonable" to start i.v. BPs in women with localized pain whose bone scans were abnormal and plain radiographs normal, but not when an abnormal bone scan is asymptomatic. The pertinence of these criteria is discussed below. Because BPs are providing supportive care, reducing the rate of skeletal morbidity but evidently not abolishing it, the criteria for stopping their administration have to be different from those used for classic antineoplastic drugs, and they should not be stopped when metastatic bone disease is progressing. However, criteria to determine whether and for how long an individual patient benefits from their administration are lacking. New biochemical markers of bone resorption might help identify those patients continuing to benefit from therapy. Even better results have been achieved in patients with multiple myeloma, and the general consensus is that BPs should be started as soon as the diagnosis of lytic disease is made in myeloma patients. On the other hand, data are scanty in prostate cancer, but large-scale trials with potent BPs are ongoing or planned in such patients. Similar results to those achieved with pamidronate have been obtained with monthly 6-mg infusions of the newer BP ibandronate in patients with breast cancer metastatic to bone. The tolerance of ibandronate could be better, and the drug has the potential to be administered as a 15- to 30-min infusion. Zoledronate can also be administered safely as a 15-min 4-mg infusion, and large scale phase III trials have just been completed. These newer BPs will simplify the current therapeutic schemes and improve the cost-effectiveness ratio; they also have the potential to improve the therapeutic efficacy, at least in patients with an aggressive osteolytic disease or when given as adjuvant therapy. For that matter, initial data with clodronate indicate that they have the potential to prevent the development of bone metastases, but the use of BPs in the adjuvant setting must still be viewed as experimental.
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PMID:Bisphosphonates for cancer patients: why, how, and when? 1213 23

Percutaneous vertebroplasty is a minimally invasive procedure that is effective in the treatment of pain resulting from pathologic compression fractures, osteolytic bone metastases from solid tumors, myeloma, vertebral hemangioma, and osteoporotic compression fractures. A discussion of a patient with severe, aggressive metastatic breast cancer to the spine with compression and osteolysis of multiple lumbar vertebral bodies is presented. Despite treatment with opiates, chemotherapy, radiation therapy, and the implantation of a morphine pump, her pain was not adequately treated until she underwent multilevel vertebroplasty. The clinical and technical application of vertebroplasty in the context of the management of vertebral pain of malignant origin is presented as an integral part of multidisciplinary pain management.
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PMID:Percutaneous vertebroplasty in the management of a patient with malignant pain and associated osteolytic compression fractures. 1241 2

The two main therapeutic applications of bisphosphonates are tumour bone disease and osteoporosis. They constitute the standard treatment for cancer hypercalcaemia, and placebo-controlled trials have shown that the prolonged administration of bisphosphonates, such as pamidronate or clodronate, can reduce the frequency of complications from tumour bone disease due to metastatic breast cancer or myeloma by a quarter to one-half. The results obtained with the intravenous route appear to be more impressive and more rapidly obtained than with oral compounds. Both agents can reduce the risk of vertebral, wrist and hip fractures by 30 - 50%, whereas other antiresorptive agents, such as raloxifene (Eli Lilly & Co.) or calcitonin (Unigene Laboratories Inc.), have only been demonstrated to reduce the incidence of vertebral fractures. The short infusion time (4 mg over 15 min) offers a convenient therapy and constitutes the most evident advantage of zoledronic acid, which will improve patients' quality of life. Zoledronic acid has the potential to change the treatment of osteoporosis dramatically.
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PMID:Zoledronic acid: an advance in tumour bone disease therapy and a new hope for osteoporosis. 1266 19

The objective of this article is to report upon a simple technique of bone marrow specimen collection of intramedullary bone tumors using a pediatric chest tube. This technique is described along with two case reports which include a 60-year-old female with metastatic breast cancer to the proximal femur, and a 63-year-old male with multiple myeloma of the proximal humerus. Utilizing this technique, in our experience, over 50 mL of aspirate can be obtained and definitive histologic material for cytogenetic diagnosis and immunohistochemistry. This technique is not indicated for biopsy of suspected primary lesions of bone due to the possibility of medullary or hematologic seeding and inappropriate invasion of soft tissue compartments.
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PMID:Bone marrow sampling in pathologic fractures: intramedullary pediatric chest tube technique. 1510 53

Ibandronate is a third-generation aminobisphosphonate that has an excellent safety record in hypercalcaemia of malignancy, and has recently been approved for the prevention of skeletal events from metastatic breast cancer. This paper reviews the safety data from clinical studies of intravenous ibandronate by infusion or injection, focusing on renal adverse events (AEs). In clinical trials of patients with hypercalcaemia of malignancy, 2-h infusions of ibandronate at doses of up to 6 mg had a low potential for renal events. In a phase III trial of patients with metastatic bone disease from breast cancer, 6 mg ibandronate infused over 1-2 h had a renal safety profile comparable to that of placebo. In pilot studies, repeated daily infusions of ibandronate (4 mg infused over 2 h for four consecutive days, or 6 mg infused over 1 h for three consecutive days) for severe metastatic bone pain were not associated with any renal AEs. The safety of single 15-min infusions of 6 mg ibandronate has been demonstrated in healthy volunteers and patients with metastatic bone disease from breast cancer or multiple myeloma. Furthermore, single and rapid bolus injections of 2 or 3 mg ibandronate did not increase the risk of renal dysfunction in patients with skeletal metastases. Implications for the renal safety of ibandronate in the management of patients with metastatic bone disease are discussed.
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PMID:Rapid administration of ibandronate does not affect renal functioning: evidence from clinical studies in metastatic bone disease and hypercalcaemia of malignancy. 1537 22

Experimental studies have demonstrated that thalidomide has anti-tumor activity mediated by blockage of angiogenesis, with clinical efficacy in multiple myeloma, glioblastoma multiforme, and renal cell cancer. We investigated the therapeutic activity and toxicity of thalidomide in patients with progressive metastatic breast cancer pretreated with chemotherapy. Inclusion criteria were metastatic breast cancer in progression of disease after at least two lines of chemotherapy, age > or = 18 years, performance status < or = 2, and adequate hematologic, renal, and hepatic functions. Twelve patients entered the study, eight of whom were pretreated with three or more lines of chemotherapy (66.7%). Thalidomide was well tolerated: the most common side effects were constipation and somnolence (58.3% of patients). No objective response or durable stable disease was observed. Median time to progression and median overall survival were 8 weeks (range, 4-10 weeks) and 16 weeks (range, 8-54 weeks), respectively. In conclusion, thalidomide is an ineffective treatment in patients with progressive metastatic breast cancer heavily pretreated with chemotherapy.
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PMID:Thalidomide is inactive in heavily pretreated patients with metastatic breast cancer. 1605 69

A case is presented of symptomatic hypocalcemia following treatment with bisphosphonates. This patient also had deficiency of 25 hydroxyvitamin D that was unrecognized. The use of bisphosphonates in cancer is increasing, not only in the treatment of hypercalcemia, but also for bone pain and to decrease the risk of skeletal morbidity in metastatic breast cancer, multiple myeloma, and Paget's disease in normocalcemic patients. The patient was probably vitamin D deficient because of a combination of poor oral intake, inadequate sunlight exposure, and the development of renal failure. However despite receiving both parenteral and oral calcium therapy, the serum calcium remained low until the replacement of vitamin D. With increasing use of bisphosphonate therapy in malignant disease, we believe that an assessment of vitamin D status, calcium intake, renal function, phosphate, magnesium, and albumin should be undertaken prior to initiating therapy in most palliative care patients.
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PMID:Bisphosphonate-induced hypocalcemia associated with vitamin D deficiency in a patient with advanced cancer. 1622 61

Osteochemonecrosis of the jaws is a well described side effect of bisphosphonate therapy. Bisphosphonates are non metabolised analogues of pyrophosphate that are capable of localizing to bone, slowing both rate of growth and rate of dissolution therefore reducing the rate of bone turnover. Although the exact mechanism is not clear but it has been established that bisphosphonates target osteoclast, inhibiting their function in several ways: There are two types of bisphosphonates. The first are oral preparations of bisphosphonates, which include Alendronate and Risedronate. They are indicated for the treatment of osteoporosis. They are considered as lower risk of osteochemonecrosis. The second are administered intravenously. Pamindronate is a first generation bisphosphonate; 90 mg administered intravenouly over 2-24 hours every 3-4 weeks. The next generation of intravenous bisphosphonate is Zoldronic acid, which is more effective than Pamidronate in controlling hypercalcaemia of bone and reducing the skeletal related events in patients with metastatic breast cancer, multiple myeloma, hypercalcaemia of malignancy, paget's disease and bone metastasis from prostate and lung cancer.
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PMID:Osteochemonecrosis of jaws and bisphosphonates. 1749 45

PS-341, now known as bortezomib (Velcade[Millenium Pharmaceuticals, Inc., Cambridge, MA; and Johnson & Johnson Pharmaceutical Research & Development, LLC, Spring house, PA]), is a proteasome inhibitor approved for the treatment of refractory multiple myeloma. Preclinical and early clinical studies showed PS-341 to be effective in solid tumors, one of which was breast cancer. We conducted a single institution, phase II study using PS-341 in the treatment of patients with metastatic breast cancer. The primary objective of this study was to determine the objective tumor response in patients with metastatic breast cancer (MBC) receiving PS-341. The secondary objectives were to estimate progression-free survival of patients receiving single-agent PS-341 and to evaluate toxicity related to PS-341. In all 12 patients who met criteria for enrollment, there were no observed objective responses. Further, all 12 patients progressed while receiving therapy with PS-341. This study was terminated after the first stage due to the lack of any objective response.
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PMID:A phase II study of single agent bortezomib in patients with metastatic breast cancer: a single institution experience. 1795 40

Receptor activator of nuclear factor-kB (RANK), its ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) together play a key role in osteoclastogenesis. Alterations in the RANKL/ OPG ratio are central in the pathogenesis of bone loss, from osteoporosis in all its forms to malignancy-induced bone loss. This fact has led to the search for drugs capable of targeted RANKL inhibition in the management of skeletal disorders associated with bone loss. Promising preclinical data using OPG have paved the way for the development of the new agent denosumab, a high-affinity, high-specificity, fully human monoclonal antibody to RANKL, shown to be able to induce a dose-dependent, rapid, profound and sustained inhibition of bone resorption lasting for months after a single subcutaneous injection in healthy postmenopausal women, men and patients with multiple myeloma or metastatic breast cancer. Data from a phase II study in postmenopausal women with low bone mineral density (BMD) demonstrate that the sustained inhibition of bone resorption induced by three or six monthly subcutaneously administered denosumab was associated with significant increases in BMD for up to two years of treatment. Antifracture efficacy and long-term skeletal and extraskeletal safety of denosumab are being addressed in ongoing phase III trials. The potential of denosumab to prevent bone loss has also been demonstrated in malignancy-induced bone loss. Ongoing studies in rheumatoid arthritis are also promising.
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PMID:Denosumab: RANKL inhibition in the management of bone loss. 1830


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