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)

This Phase II study was designed to determine the efficacy and tolerability of vorozole (R83842), a new nonsteroidal aromatase inhibitor, in postmenopausal women with advanced breast cancer in progression being treated with tamoxifen, and to correlate these effects with the hormonal profile and plasma drug levels. Twenty-nine eligible women with estrogen receptor-positive or unknown disease were treated with 2.5 mg vorozole once daily p.o. until disease progression. All 29 are evaluable for toxicity and 27 for response as assessed by International Union Against Cancer (UICC) criteria. After a median follow-up of 8 months, 3 patients (11%) had partial remission of their disease for 14, 15, and 16 months and 14 patients had disease stabilization for 7-24 months (median, 12). Patients with a normal carcinoembryonic antigen level (</=3 mm/liter), those without bone metastases, older women, and those with a long disease-free interval were most likely to benefit from treatment. Estradiol decreased from pretreatment levels of 9. 2-85 pm/liter (mean, 24) to below detection (9.2 pm/liter) and estrone from 64-311 pm/liter (mean, 144.3) to 19-116 pm/liter (mean, 57) after 1 month. Serum follicle-stimulating and luteinizing hormone levels rose from 9-74 IU/liter (mean, 35.3) and 3.3-38 IU/liter (mean, 17.8) to 10-102 IU/liter (mean, 44.6) and 1.6-70 IU/liter (mean, 24.2) and sex hormone-binding globulin fell from 27-138 nm/liter (mean, 65.4) to 15-109 nm/liter (mean, 53.8) after 1 month of treatment. Corresponding levels of androstenedione, dehydroepiandrosterone, free testosterone, and 17alpha-hydroxyprogesterone were unaffected. An adrenocorticotropic hormone stimulation test was normal in 18 patients 1 month after treatment commenced. Trough drug levels (measured by gas chromatography) ranged from 6.5-95 ng/ml (median, 24.5) at 1 month of treatment. Possible treatment-related side effects were mild and included malaise, anorexia and nausea, hot flashes, fluid retention, vaginal infection, alopecia, lightheadedness, and one allergic reaction which caused lip swelling. Vorozole, given orally, is a clinically active well-tolerated new treatment for breast cancer. Selective suppression of estrogen confirms its action as a specific aromatase inhibitor. Further trials to confirm its relative efficacy in postmenopausal disease and to explore its application in other settings are indicated.
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PMID:Phase II study of vorozole (R83842), a new aromatase inhibitor, in postmenopausal women with advanced breast cancer in progression on tamoxifen. 981 84

A 67-year-old man presented with malaise and marked anemia. A diagnostic workup revealed severe pancytopenia on a complete blood count and diffuse sclerotic change in the axial skeleton on a plain abdominal radiograph. Bone metastases being suspected from these findings, bone scintigraphy was performed. The bone scan demonstrated uniformly increased skeletal activity with faint soft-tissue activity. The findings of the bone scan, however, appeared atypical of the super scan caused by diffuse bone metastases, without any decrease in radioactivities of the appendicular skeleton and kidneys. Bone marrow scintigraphy with In-111 chloride demonstrated central marrow failure and peripheral expansion, which indicated the possibility of myelophthisis. The patient underwent bone marrow biopsy, which revealed replacement of the bone marrow by metastatic adenocarcinoma. Further examinations detected the primary lesion in the prostate. In this case, the findings of the bone scan were insufficient for the super scan, and might be categorized as a sub-super scan. It would be important to recognize this incomplete form of super scan as a rare scintigraphic pattern of diffuse bone marrow metastases.
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PMID:Sub-super bone scan caused by bone marrow involvement of prostate cancer. 1058 6

Hypercalcaemia is a well-recognised feature of hypoadrenalism. The adrenal glands are often involved with metastatic disease subclinically although full hypoadrenal crisis is not uncommon. Ill patients with known malignancy should generate a high degree of clinical suspicion for the possibility of adrenal involvement. This case highlights the need to look beyond confirmed bone metastases as the cause of hypercalcaemia in patients with widespread carcinomatosis.
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PMID:Hypercalcaemia of hypoadrenal crisis mistaken for hypercalcaemia of malignancy in a patient with known bone metastases: a case report. 1111 62

Denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor-kappa B ligand (RANKL), suppresses bone resorption. This open-label, multicenter, phase 1 study evaluated the safety, pharmacodynamics, and pharmacokinetics of denosumab in Japanese women with breast cancer-related bone metastases. Patients (n = 18; median age, 57 years) received a single subcutaneous injection of denosumab 60 mg or 180 mg or three doses of denosumab 180 mg on days 1, 29, and 57 (every 4 weeks) and were followed for > or = 141 days. No major safety concerns related to denosumab were noted in any cohort. All patients experienced at least 1 adverse event (AE); most were mild (grade < or = 2). One patient reported grade 4 myositis and grade 3 anemia, malaise, and dysphagia that the investigator deemed treatment-related; other treatment-related AE were grade < or = 2. No antidenosumab antibodies or clinically significant changes in laboratory findings, vital signs, or electrocardiograms were observed. Pharmacokinetics were approximately dose-linear. Denosumab caused rapid, substantial, and sustained suppression of urinary N-telopeptide corrected for creatinine (uNTx/Cr) across all doses; at day 85, the median change from baseline uNTx/Cr ranged from -61.9% to -90.8%. No dose-limiting toxicity was observed at any dosage. Coupled with pharmacokinetic and pharmacodynamic data, these results were consistent with those observed in non-Japanese populations.
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PMID:Phase 1 trial of denosumab safety, pharmacokinetics, and pharmacodynamics in Japanese women with breast cancer-related bone metastases. 1842 61

We herein report a 75-year-old patient with recurrent hormone-nonresponsive, HER2-positive breast cancer who presented with multiple lung metastases. She had undergone a mastectomy followed by adjuvant chemotherapy with FEC, CMF, and UFT. Forty-six months after the surgery, multiple lung, liver, and bone metastases were observed. Docetaxel and trastuzumab were administered as first-line chemotherapy for 13 months. A partial response and stable disease were observed, but progressive disease in the lung and brain was subsequently revealed. The patient then underwent g-knife treatment for brain metastasis. Lapatinib and capecitabine treatment was administered as second-line chemotherapy for 9 months. Stable disease was observed, but progressive disease in the lung metastases with clinical symptoms including cough, exertional dyspnea, and general malaise was revealed. As third-line chemotherapy, the patient was administered low-dose, bi-weekly nab-paclitaxel(150mg/m2)and trastuzumab therapy. Four weeks after beginning the nab-paclitaxel and trastuzumab treatment, the cough disappeared; 2 months after beginning the therapy, a partialresponse in the lung metastases was seen. The patient is well and the treatment has been continued for 50 weeks. No progression has been seen. Bi-weekly nab-paclitaxel treatment appears to have few side effects and might be an effective treatment option for patients with recurrent breast cancer.
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PMID:[Bi-weekly nab-paclitaxel and trastuzumab therapy effective against recurrent breast cancer with multiple lung metastases in elderly patient who had previously undergone two chemotherapeutic regimens for treatment of metastatic disease-a case Report]. 2315 23

A 42-year-old woman visited our hospital with high fever and general malaise. A CT examination revealed that she had carcinoma of the left breast with axillary lymph node metastases and multiple bone metastases. A blood test showed anemia, thrombopenia and the existence of blast-like cells. Adenocarcinoma cells were detected in a bone marrow aspiration specimen, and the patient was diagnosed with disseminated carcinomatosis of the bone marrow. Systemic chemotherapy with paclitaxel plus bevacizumab was initiated while a blood transfusion was performed. Her symptoms improved, and the blood test results normalized. Disseminated carcinomatosis of the bone marrow is reported to have a poor prognosis, but paclitaxel plus bevacizumab is a possible effective chemotherapy.
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PMID:[A Case of Disseminated Bone Marrow Carcinomatosis Arising from Breast Cancer for Which Paclitaxel and Bevacizumab Treatment Was Effective]. 2680 35

We report a case of a 42-year-old woman with bone marrow carcinomatosis in the course of metastatic breast cancer who responded well to paclitaxel plus bevacizumab(PTX plus Bev)combination therapy. Four years after initial breast conserving surgery, she was admitted to our hospital with back pain and general malaise and was diagnosed as multiple bone metastases with bone marrow carcinomatosis originating from previous breast cancer(ER+/HER2-). While administering denosumab, we initiated systemic chemotherapy with PTX plus Bev. There has been no sign of progression at 1 year after beginning the treatment. Therefore, we conclude that PTX plus Bev combination therapy could be effective and sustainable treatment for bone marrow carcinomatosis arising from metastatic breast cancer.
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PMID:[Clinical Efficacy of Paclitaxel plus Bevacizumab Combination Therapy for Bone Marrow Carcinomatosis Arising from Breast Cancer - A Case Report]. 2939 44