Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new derivative of ellipticine, hydroxy-9-methyl-2-ellipticinium acetate, was found to be a useful anti-tumor drug in advanced cancers which could not be treated any longer successfully by any other procedure. In our series of 100 patients, the best results were obtained with bone metastases from breast carcinomas and with anaplastic thyroid carcinomas. Most patients usually received a weekly perfusion of 80 mg/m2. The main characteristic of this drug is its lack of hematologic, and hepatic toxicity. No renal trouble was observed during the first year, but 2 deaths from renal insufficiency occured during the 18th and 15th month of treatment. The most frequent side effect consists of digestive troubles (nausea, vomiting) which rarely compelled to stop the treatment (4 times in 100 patients).
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PMID:[Hydroxy 9-methyl 2-ellipticinium acetate (NSC 264-137). Toxicologic study and therapeutic effect in 100 cancers (author's transl)]. 47 24

Six breast cancer patients were treated recently for renal insufficiency secondary to neoplasic involvement of the ureters. This complication usually occurs in long standing hormonal-dependent breast cancer with bone metastases. Diagnosis was performed by abdominal echography. Ureteral catheterization or percutaneous nephrostomy with or without irradiation always resulted in rapid recovery of renal function. Systemic chemotherapy could then be given, sometimes with antitumoral responses, allowing the removal of the endoureteral catheters.
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PMID:Ureteral obstruction in patients with breast cancer. 335 80

A group of 135 patients with osseous metastases from breast cancer were treated with hydroxy-9-methyl-2-ellipticinium (100 mg/m2 weekly). Although it was impossible to grade the response precisely, because only indirect criteria are available for assessing the course of bone metastases (radiographs, quantified 99mTc pyrophosphate scintigrams, CEA), it was considered that an objective response was obtained in 44 cases. These responses lasted from 3 to 17 months. The main characteristic of the compound is its lack of marrow toxicity, a valuable property in osseous lesions, where frequent marrow involvement makes it difficult to use conventional drugs. The major and most unpleasant side effect was an inhibition of salivary secretion, which causes other complications such as tongue mycosis, anorexia, and asthenia. Immunologic disorders were less frequent, and four patients developed severe tubular renal insufficiency.
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PMID:Hydroxy-9-methyl-2-ellipticinium for osseous metastases from breast cancer: a 5-year experience. 713 36

Bone metastases are a common cause of morbidity in patients with breast cancer. In an open, phase II, non-comparative trial to investigate the effects of repeated infusions of pamidronate (Aredia) on pain, mobility, analgesic consumption, bone healing and bone metabolism, 69 patients with breast cancer and bone metastases received pamidronate 60 mg intravenously in 250 ml normal saline over 1 or 4 hours every 2 weeks for a total of 13 infusions, until either progressive disease or a serious adverse event. Improvement in pain score was seen in 33 of 54 evaluable patients (61%) as measured by a linear analogue pain scale, and in 28 of 56 evaluable patients (50%) as measured on a 6-point pain scale: 18 (30%) of 60 evaluable patients showed reduction in a 6-point analgesic score, while 28 patients (50%) showed some improvement in mobility, as assessed by a questionnaire. Sclerosis appeared in > 25% of bone lesions in 2 patients and in < 25% of bone lesions in 12 patients. Urinary calcium/creatinine ratios fell dramatically during therapy. One patient developed symptomatic hypocalcemia, 1 showed deterioration in pre-existing renal insufficiency. Fever occurred in 19% of patients, and less than 20% developed flu-like symptoms. We conclude that intravenous infusions of pamidronate at a dose of 60 mg every 2 weeks produces a marked reduction in pain in patients with extensive bone metastases from breast cancer.
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PMID:Role of pamidronate in the management of bone metastases from breast cancer: results of a non-comparative multicenter phase II trial. Aredia Multinational Cooperative Group. 753 92

Tumour-induced hypercalcaemia (TIH) is a frequent complication of advanced cancer but has been rarely reported in patients with malignant melanoma, and its pathogenesis remains unexplored. We studied eight patients with TIH and melanoma. We determined the incidence and pathogenesis of this complication and the effects of bisphosphonate therapy. The incidence of TIH in 751 patients with melanoma was 1.1%. All patients had liver and bone metastases at the time of hypercalcaemia. All patients had osteolytic lesions, most often multiple. The median survival was 30 days (range 4-136 days). After rehydration, the mean (+/- SEM) corrected calcium was 3.42 +/- 0.17 mmol/l. Parathyroid hormone levels were adequately suppressed and vitamin D concentrations were normal. Serum osteocalcin, a marker of bone formation, was low, except in the two patients with renal insufficiency, whereas fasting urinary calcium and hydroxyproline were increased, indicating inhibition of bone formation and stimulation of bone resorption. Increased parathyroid hormone-related protein secretion was noted in only one patient. Three of four patients became normocalcaemic after bisphosphonate therapy for a median duration of 2 weeks. In conclusion, hypercalcaemia is a rare complication of melanoma. It occurs in the context of far advanced disease and is essentially due to aggressive lytic bone metastases with an uncoupling in bone turnover. Bisphosphonates can offer short-term palliation.
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PMID:Hypercalcaemia of melanoma: incidence, pathogenesis and therapy with bisphosphonates. 1159 84

Beta-emitting, bone-seeking radiopharmaceuticals, administered systemically, represent a good alternative or adjuvant to external beam radiotherapy for palliation of painful osteoblastic bone metastases. The most frequently used radiopharmaceutical for this purpose is strontium 89, followed by samarium 153 ethylenediaminetetramethylene phosphonate, and infrequently phosphorus 32 orthophosphate. Prior to consideration for radionuclide therapy, recent bone scans should be evaluated in order to determine if the patient has painful osteoblastic lesions likely to respond to therapy. Approximately 70% of patients with prostate and breast cancer will have a reduction in pain in response to radionuclide therapy, beginning within 2 to 4 weeks and lasting between 2 and 6 months. Patients who are expected to live 3 or more months are more likely to benefit than patients with shorter duration life expectancy. Hematosuppression is the chief side effect of radionuclide therapy, with leukopenia and thrombocytopenia more likely to be clinically significant than anemia. Relative contraindications for treatment include osteolytic lesions, pending spinal cord compression or pathologic fracture, preexisting severe myelosuppression, urinary incontinence, inability to follow radiation safety precautions, and severe renal insufficiency.
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PMID:Radionuclide therapy for palliation of pain due to osteoblastic metastases. 1585 38

Incidence and mortality of prostate cancer increase with age. This epidemiologic trend and disease's natural history, extending on 10 to 15 years, explain that a majority of patients are old (more than 70 years) to very old (more than 80 years) at the metastatic stage. Moreover, when a geriatric screening is done, oncogeriatric parameters are often disturbed, justifying both an oncologic and a geriatric approaches. But the strength of co-morbidities does not justify a systematic under-treatment, because a patient older than 70 years and suffering from prostate cancer on two will die from his cancer, often with a painful symptomatology. As for a younger patient, the disease is hormono-sensitive during 18 to 24 months, before it becomes androgeno-resistant. The treatment, simple castration, complete hormonal blocking or anti-androgens alone, was not evaluated specifically in the elderly. Clinical and biological response to hormonal manipulation is often short and this procedure should not delay chemotherapy, when patient's clinical status allows it, in order mainly to reduce clinical symptoms. Docetaxel showed, in TAX427 study, a better control of clinical symptoms than mitoxantrone and also an increase in patients'survival. In the subgroup of patients older than 70, hematologic toxicities are more frequent and justify a G-CSF prophylaxy, according to international recommendations; on the opposite, non-hematologic toxicities are as frequent as in the younger subgroup. When bone metastases are symtomatic, some treatments can associate or follow a chemotherapy: bisphosphonates, radiotherapy and metabolic radiotherapy. These treatments have specific toxicities and must be specifically supervised in the elderly (bisphosphonates can worsen a renal insufficiency and metabolic radiotherapy induces frequently a limitant hematotoxicity). Lastly, new molecules are currently under evaluation. Current or future studies, according to international recommendations, must include elderly patients and avoid restrictive exclusion criteria.
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PMID:[Metastatic prostate cancer treatment in the elderly]. 1784 98

Patients with multiple myeloma (MM) experience pathologic fractures, bone pain, hypercalcemia, neurologic symptoms, and renal insufficiency with substantial morbidity and mortality. Bisphosphonates have been used successfully for the management of MM-related bone disease. Increased incidence of osteonecrosis of the jaw has been observed in patients with cancer receiving bisphosphonate therapy. Recent advances in the pathobiology of MM-related bone disease and other cancer-related bone metastases have led to the identification of novel therapeutic targets, such as receptor activator of nuclear factor-kappaB (RANK); its ligand (RANKL); and a decoy receptor, osteoprotegerin, for the development of potential targeted agents. Initials studies have demonstrated that targeting RANK/ RANKL signaling with the fully human monoclonal antibody denosumab prevented skeletal complications in patients with MM and other cancers with bone metastases. Ongoing studies evaluating the clinical utility of denosumab in cancer- related bone destruction have been discussed. In addition, several potential targets, such as macrophage inflammatory protein-1alpha, chemokine receptors 1 and 5, interleukin-3, and Wnt signaling, are b riefly described.
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PMID:Novel approaches in the management of myeloma-related skeletal complications. 1863 61

Bisphosphonates are valuable agents for the treatment of post-menopausal osteoporosis (PMO), hypercalcemia of malignancy, and osteolytic bone metastases. Oral bisphosphonates are used mainly to treat PMO and are not associated with significant nephrotoxicity. In contrast, nephrotoxicity is a significant potential limiting factor to the use of intravenous (IV) bisphosphonates, and the nephrotoxicity is both dose-dependent and infusion time-dependent. The two main IV bisphosphonates available to treat hypercalcemia of malignancy and osteolytic bone disease in the United States are zoledronate and pamidronate. Patterns of nephrotoxicity described with these agents include toxic acute tubular necrosis and collapsing focal segmental glomerulosclerosis, respectively. With both of these agents, severe nephrotoxicity can be largely avoided by stringent adherence to guidelines for monitoring serum creatinine prior to each treatment, temporarily withholding therapy in the setting of renal insufficiency, and adjusting doses in patients with pre-existing chronic kidney disease. In patients with PMO, zoledronate and pamidronate are associated with significantly less nephrotoxicity, which undoubtedly relates to the lower doses and longer dosing intervals employed for this indication. Ibandronate is approved in the US for treatment of PMO and in Europe for treatment of PMO and malignancy-associated bone disease. Available data suggest that ibandronate has a safe renal profile without evidence of nephrotoxicity, even in patients with abnormal baseline kidney function.
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PMID:Bisphosphonate nephrotoxicity. 1868 74

The Renal Insufficiency and Anticancer Medications (IRMA) study is a French national, observational study which demonstrated the high prevalence of abnormal renal function in a population of 4,684 solid tumour patients. Among them, 50-60% had decreased renal function defined as CrCl below 90 and 80% were treated with anticancer drugs that either necessitated dosage adjustment in case of RI or were potentially nephrotoxic drugs. Since patients and drugs used differ depending on the type of tumour, the IRMA Study Group started analyses in different subgroups of patients. In the 1898 IRMA patients with breast cancer, the prevalence of RI was still very high in spite of a normal serum creatinine in almost all cases. Some anticancer drugs, as in particular some bisphosphonates, capecitabine and platinum salts, may be nephrotoxic and/or need dosage adjustment. However other important drugs in breast cancer do not require dose reduction, and do not present with potential nephrotoxicity (anthracyclines, taxanes, trastuzumab). Both issues seem to be slightly but significantly more important in patients with bone metastases as compared to patients with a non-metastatic disease.
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PMID:Prevalence of renal insufficiency in breast cancer patients and related pharmacological issues. 1870 81


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