Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum beta-2 microglobulin levels were measured in normal individuals and in breast cancer patients. It was observed that there was a significant rise in levels especially in advanced stages of the disease. It was concluded that patients with a beta-2 microglobulin/creatinine ratio of greater than 3.8 were likely to have metastatic breast cancer.
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PMID:Study of serum beta-2 microglobulin levels in breast cancer patients. 9 58

In an effort to explore the use of polypeptide growth factors as potential markers for cancer detection, we have identified the presence of transforming growth factor-alpha (TGF-alpha) in pooled urine of patients with metastatic breast cancer by a commercial radioimmunoassay (RIA) based on a rabbit antiserum raised to the C-terminal 17aa synthetic fragment of rat TGF-alpha. This TGF-alpha RIA detected both high molecular weight (HMW) and low molecular weight (LMW) forms of TGF-alpha in the conditioned media of a breast cancer cell line (MDA-MB-231) and in the urine of healthy women and those with breast cancer. The ratio of HMW to LMW species of TGF-alpha by RIA after Bio-Gel P-100 chromatography was approximately equal in pooled urine samples from both healthy women and those with breast cancer, and in the conditioned media from the cell line MDA-MB-231. Using established procedures for concentrating urinary proteins from 24-h urine samples by adsorption onto methyl-bonded microparticulate silica and selective elution by acetonitrile, TGF-alpha RIA results from women with disseminated breast carcinoma were compared with those of healthy pre- and post-menopausal control women. Analysis indicated a median TGF-alpha value of 981 ng/g urinary creatinine for urine samples from cancer patients (range 608 to 1737) and 642 ng/g creatinine (range 417 to 941) for control urine samples. Although the difference was statistically significant (p less than 0.05), urinary TGF-alpha detection with this assay method appears to have limited usefulness as a diagnostic marker for metastatic human adenocarcinoma of the breast.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of urinary transforming growth factor-alpha in women with disseminated breast cancer and healthy control women. 179 34

Pharmacokinetic analysis of epirubicin and its metabolites epirubicinol and 7-deoxy-13-dihydro-epirubicinol aglycone during the first and the fourth courses of treatment was performed in 78 patients with metastatic breast cancer. The patients were treated every 3 weeks with epirubicin given as 10-min i.v. infusions at four different dose levels: 40, 60, 90 and 135 mg/m2. In most cases (76 of 78 cases), plasma concentration-time curves fitted to a three-compartmental pharmacokinetic model. The terminal half-life of epirubicin was independent of dose and duration of treatment. Large interindividual differences were demonstrated (mean t1/2 gamma, 21.6 +/- 7.9 h; range, 10.6-69 h; n = 110). In two subjects, extremely long half-lives and high serum bilirubin concentrations indicated impaired liver function. No correlation was found between the half-life and levels of liver alanine aminotransferase (ALAT) or serum creatinine. The metabolite epirubicinol appeared quickly after epirubicin administration and its half-lives were shorter than that of the parent compound (mean t1/2 gamma, 18.1 +/- 4.8 h; range, 8.2-38.4 h; n = 105). Formation of the aglycone metabolite was delayed and the half-life of this metabolite was shorter than that of epirubicin (mean t1/2 gamma, 13 +/- 4.6 h; range, 2.7-29 h; n = 104). The AUC of epirubicin and the total AUC (drug and metabolites) were linearly proportional to the dose, with the former value constituting two-thirds of the latter. A correlation was found between AUC and the plasma concentration of epirubicin at two time points (2 and 24 h after administration). The proposed model was AUC = 9.44 x c2 + 62.5 x c24 + 157.7 (r = 0.953).
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PMID:Multiple-dose pharmacokinetics of epirubicin at four different dose levels: studies in patients with metastatic breast cancer. 204 35

The antitumor, endocrine, hematological, biochemical, and side effects of chronic second-line treatment with the antiprogestin mifepristone (RU) 486) were investigated in 11 postmenopausal patients with metastatic breast cancer. We observed one objective response, 6 instances of short-term stable disease, and 4 instances of progressive disease. Mean plasma concentrations of adrenocorticotropic hormone (P less than 0.05), cortisol (P less than 0.001), androstenedione (P less than 0.01), and estradiol (P less than 0.002) increased significantly during treatment accompanied by a slight decrease of sex hormone binding globulin levels, while basal and stimulated gonadotropin levels did not change significantly. The increased basal cortisol levels could not be further stimulated by synacthen, nor suppressed by 1 mg of dexamethasone. Plasma estradiol concentrations were significantly correlated with both androstenedione (P less than 0.05) and cortisol levels (P less than 0.01). The percentage of eosinophilic white blood cells (P less than 0.02) and mean plasma creatinine concentration (P less than 0.05) increased significantly. Side effects frequently occurred during long-term treatment and appeared to be caused mainly by the antiglucocorticoid properties of the drug. It is concluded that antiprogestins form a new treatment modality in the endocrine treatment of human breast cancer. New antiprogestins with less antiglucocorticoid side effects might be especially of value as an adjunct to antiestrogenic treatment in view of our finding that combined antiestrogenic and antiprogestational treatment caused additive growth-inhibitory effects in rat mammary tumors.
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PMID:Antiprogestins, a new form of endocrine therapy for human breast cancer. 272 Jun 45

In 1976 we isolated a novel glycoprotein labeled EDC1, Mr 27,500, which is immunologically related to the normal plasma protein inter-alpha trypsin inhibitor (IATI, Mr 160,000) and which is the major component of cancer-associated proteinuria. Urinary excretion of EDC1 (mg/g creatinine) may be classified in four ranges: i) low (less than 15); ii) light (15-30); iii) intermediate (31-45); and iv) heavy (greater than 45). Normal healthy women excrete 8.0 +/- 2.2 mg/g creatinine (average +/- SEM), whereas patients with metastatic breast cancer excrete 98.2 +/- 11.6 mg/g creatinine. Patients with a variety of non-malignant disorders excreted 14.6 +/- 4 mg EDC1/g creatinine, but patients with renal failure, rheumatoid arthritis, and infectious diseases averaged 130.3 +/- 60. Sixty-five to 95 percent of urinary immunoreactive EDC1 in the latter group was of higher molecular weight, perhaps reflecting increased renal clearance of plasma IATI. In patients undergoing excisional biopsy of breast lesions, preoperative EDC1 excretion was 21.5 +/- 3.4 in those whose lesions were benign and 43.1 +/- 7.6 in those whose lesions were malignant. Eight of these latter patients were heavy excretors; EDC1 excretion fell postoperatively in these patients. In normal serum the immunoreactive IATI (IR-IATI) exists in three molecular weight forms 160,000, 120,000 and 58,000. In patients who were heavy excretors of EDC1, the IR-IATI corresponding to Mr 58,000 was absent and total serum IR-IATI was about two-thirds of normal. There was also a negative correlation between serum levels of IATI and urinary EDC1 in these patients. These data suggest that urinary EDC1 may arise as a result of interaction between IATI and tumor-associated proteases.
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PMID:Urinary cancer-related protein EDC1 and serum inter-alpha trypsin inhibitor in breast cancer. 608

Carboplatin (CBDCA; NSC 241240) is a second-generation platinum coordination compound which in preclinical testing was found to be less nephrotoxic and emetogenic than cis-diamminedichloroplatinum (CDDP), while retaining a broad spectrum of antitumor activity. We have conducted a Phase I trial of CBDCA in 38 patients with advanced carcinoma. The drug was given without hydration as a 24-hr constant i.v. infusion on Day 1 of a 28-day cycle. Seventy-five cycles of CBDCA were administered in eight dose levels ranging from 20 to 320 mg/sq m. Dose-limiting toxicity was myelosuppression, primarily thrombocytopenia, occurring between Days 14 and 28 of the cycle. Myelosuppression was first observed at a dose of 240 mg/sq m and became dose-limiting at 320 mg/sq m, which is the recommended dose for Phase II trial. Other toxicities included nausea and vomiting and reversible renal failure seen in two patients with low normal pretreatment creatinine clearances. No consistent changes were seen on serial audiograms. Plasma concentrations of total and ultrafilterable platinum were measured by flameless atomic absorption spectrophotometry. Following cessation of the infusion, a half-life of 170 +/- 34 min (S.D.) was found for CBDCA-derived ultrafilterable platinum. In vitro clonogenic assay of a CDDP-sensitive human ovarian cancer cell line using clinically achievable drug concentrations suggests that prolonged infusions of CBDCA may be more cytotoxic than bolus administration. In this study, minimal responses were seen in two patients with ovarian carcinoma who had failed previous combination chemotherapy including CDDP. In addition, three patients with refractory metastatic breast cancer responded to CBDCA (two minimal responses and one partial response) with remission durations averaging 3 months. CBDCA behaves as predicted by preclinical studies with different toxicities from CDDP and apparent activity in breast cancer.
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PMID:A phase I and pharmacokinetic study of diamminecyclobutane-dicarboxylatoplatinum (NSC 241240). 634 73

A phase II clinical trial was set up in metastatic breast cancer patients who had not received previous cytotoxic drug therapy, involving the administration of cis-dichlorodiammine platinum (cis-DDP). Patients aged up to 75 years and with pathohistologically confirmed disease were entered on the trial. All patients had measurable disease, a performance status (Karnofsky) of greater than 40, and an expected survival of greater than 6 weeks. In all 38 patients entered the trial, and 35 have been evaluated. The predominating metastatic sites included soft tissues (19), visceral organs (12), and bones (7 patients). cis-DDP was administered in a daily dose of 30 mg/m2 IV by a 4-h drip for 4 days, with customary hyperhydration. The results indicate a pronounced antitumorigenic effect of cis-DDP and a response rate of 54% (19/35), with 13 complete remissions (37%) and six partial remissions (17%). In terms of site the best response was obtained in soft-tissue processes (13/19; 68%), followed by visceral organs (4/10; 40%); the response rate was lowest in bones (2/6; 33%). The menopausal status and prior hormone therapy did not essentially influence the results of treatment, unlike previous irradiation. Patients with a lower performance status (40-70) had a significantly lower response rate (36% vs 63%; P less than 0.05). Toxic side-effects were moderate and did not substantially affect the general condition of the patients. A transient increase of serum creatinine was observed in 4 patients, and neurotoxicity in 2 patients. The results of the trial warrant the conclusion that cis-DDP has a pronounced antitumorigenic effect in untreated metastatic breast cancer, particularly in soft-tissue metastases. These results call for additional clinical study of the cytotoxic effect of cis-DDP in untreated metastatic breast cancer.
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PMID:Phase II clinical trial of cis-dichlorodiammine platinum (cis-DDP) for antitumorigenic activity in previously untreated patients with metastatic breast cancer. 668 1

Because of their high affinity for bone, bisphosphonates are used both in the treatment of benign and malignant bone disease and in radiopharmaceutical bone imaging. A prospective study was undertaken to evaluate whether intravenous clodronate (dichloromethylene bisphosphonate) therapy might affect the results of bone scintigraphy with 99mTc-labeled methylene diphosphonate (MDP). In 11 female patients with breast cancer and metastatic bone disease, quantitative bone scans were obtained using a region of interest (ROI) method on Days 0 and 22. After intravenous clodronate therapy from Day 1 to Day 21, all metastatic bone lesions were still detectable, and median ROI ratios did not differ to a statistically significant extent from baseline values. Serum calcium levels decreased (p = 0.0449), whereas parathyroid hormone concentrations showed an increase (p = 0.0053). Mean serum levels of creatinine, inorganic phosphorus, osteocalcin, gamma glutaminyl-transpeptidase and alkaline phosphatase remained unchanged. However, a more than twofold rise in the serum activity of alkaline phosphatase was measured in three patients. We conclude that 3 wk of intravenous clodronate treatment did not impair the sensitivity of 99mTc-MDP bone scintigraphy in detecting bone lesions in patients with metastatic breast cancer.
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PMID:Effect of clodronate treatment on bone scintigraphy in metastatic breast cancer. 866 85

The experience with single-agent gemcitabine in advanced or metastatic breast cancer is reviewed. In all studies, gemcitabine was administered as a 30 min intravenous infusion in cycles once a week for 3 weeks followed by 1 week of rest. In the first European study (gemcitabine 800 mg/m2/week), of 40 evaluable patients, 14 were chemo-naive, 7 had received adjuvant chemotherapy, and 19 had received chemotherapy for metastatic disease. There were 3 complete responders and 7 partial responders (all independently validated by an external Oncology Review Board) for an overall response rate of 25.0% (95% CI: 12.7%-41.2%). The median time to declaration of response was 1.9 months and the median duration of survival for all 40 efficacy-evaluable patients was 11.5 months. Haematological and non-haematological toxicities were particularly mild. WHO grade 3 and 4 toxicities included leukopenia (6.8% and 2.3% of patients), neutropenia (23.3% and 7.0%), AST (6.8% and 2.3%), ALT (18.2% and 0%), infection (0% and 2.3%), nausea and vomiting (25.0% and 2.3%), alopecia (2.3% and 0%). There was no grade 3 or 4 creatinine, proteinuria or haematuria. In the smaller US study (18 evaluable patients, all but one having received prior chemotherapy for stage IV disease) there were no responders. However, the mean dose delivered was very low (577 mg/m2/injection). In an ongoing European trial, with a starting dose of 1000 mg/m2, a number of partial responders have been seen in soft tissue, lung and liver. Gemcitabine's modest toxicity profile and single-agent activity make it an attractive candidate for trial in combination therapy in advanced breast cancer where treatment is currently given to palliate symptoms and improve quality of life.
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PMID:Gemcitabine in advanced breast cancer. 871 26

An obese 53-year-old woman (height 167 cm, weight 130 kg) with metastatic breast cancer received high-dose chemotherapy comprising cyclophosphamide, thiotepa and carboplatin (CTC). The cyclophosphamide (1 g/m(2) per day) and thiotepa (80 mg/m(2) per day) doses were based on body surface area (BSA) calculated using total body weight (TBW). The daily carboplatin dose was calculated based on the Calvert formula, using a target area under the plasma concentration-time curve (AUC) value of 3.25 mg.min/ml and applying the Cockcroft-Gault equation to estimate the glomerular filtration rate. The patient received the three agents as short infusions over four consecutive days. For therapeutic drug monitoring (TDM), blood samples were collected on day 1. Thiotepa and its main metabolite tepa, ultrafilterable platinum, cyclophosphamide and its activated metabolite 4-hydroxycyclophosphamide were determined. Individual pharmacokinetics were assessed using Bayesian analysis. Exposure to the individual compounds was determined by calculating the AUC. Exposures to 4-hydroxycyclophosphamide, the combination of thiotepa/tepa and carboplatin were 94%, 117% and 71% higher than the median respective exposures in a non-obese population of patients ( n=24) receiving similar doses. Because high AUCs of 4-hydroxycyclophosphamide, thiotepa/tepa and carboplatin correlate with increased toxicity, the treatment risk in this obese patient was significantly increased. Therefore doses were adapted on the 3rd day of the course. It is concluded that cyclophosphamide and thiotepa in obese patients should not be dosed on the basis of BSA incorporating TBW since the patient will be overexposed. Moreover, applying the Cockcroft-Gault equation to obese patients leads to an overprediction of creatinine clearance and, when used in the Calvert equation, consequently to a carboplatin dose that is too high. Obese patients represent a unique group of patients in which TDM is extremely valuable in optimizing dosing, particularly in high-dose chemotherapy.
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PMID:Extremely high exposures in an obese patient receiving high-dose cyclophosphamide, thiotepa and carboplatin. 1220 8


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