Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phase II evaluation of anguidine was carried out in 30 patients with advanced refractory breast cancer. A dose of 5.0 mg/m2 daily for 5 days was explored. The main toxic effects were nausea and vomiting, fever and chills, hypotension, skin erythema, somnolence, confusion, and lethargy. Myelosuppression was minimal. Among these extensively pretreated patients, there was one partial responder and one additional patient who showed improvement (less than a partial response); both responses occurred in soft tissue sites.
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PMID:Phase II study of anguidine in advanced breast cancer. 45 16

Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of antineoplastic activity. It is a prodrug metabolised in the liver by cytochrome P450 mixed-function oxidase enzymes to isofosforamide mustard, the active alkylating compound. Mesna, a uroprotective thiol agent, is routinely administered concomitantly with ifosfamide, and has almost eliminated ifosfamide-induced haemorrhagic cystitis and has reduced nephron toxicity. Therapeutic studies, mostly noncomparative in nature, have demonstrated the efficacy of ifosfamide/mesna alone, or more commonly as a component of combination regimens, in a variety of cancers. In patients with relapsed or refractory disseminated nonseminomatous testicular cancer, a salvage regimen of ifosfamide/mesna, cisplatin and either etoposide or vinblastine produced complete response in approximately one-quarter of patients. As a component of both induction and salvage chemotherapeutic regimens, ifosfamide/mesna has produced favourable response rates in small cell lung cancer, paediatric solid tumours, non-Hodgkin's and Hodgkin's lymphoma, and ovarian cancer. Induction therapy with ifosfamide/mesna-containing chemotherapeutic regimens has been encouraging in non-small cell lung cancer, adult soft-tissue sarcomas, and as neoadjuvant therapy in advanced cervical cancer. As salvage therapy, ifosfamide/mesna-containing combinations have a palliative role in advanced breast cancer and advanced cervical cancer. Ifosfamide/mesna can elicit responses in patients refractory to numerous other antineoplastic drugs, including cyclophosphamide. With administration of concomitant mesna to protect against ifosfamide-induced urotoxicity, the principal dose-limiting toxicity of ifosfamide is myelosuppression; leucopenia is generally more severe than thrombocytopenia. Reversible CNS adverse effects ranging from mild somnolence and confusion to severe encephalopathy and coma can occur in approximately 10 to 20% of patients after intravenous infusion, and the incidence of neurotoxicity may be increased to 50% after oral administration because of differences in the preferential route of metabolism between the 2 routes of administration. Other adverse effects of ifosfamide include nephrotoxicity, alopecia, and nausea/vomiting. In general, intravenously administered mesna is associated with a low incidence of adverse effects; however, gastrointestinal disturbances are common following oral administration. Thus, ifosfamide/mesna is an important and worthwhile addition to the currently available range of chemotherapeutic agents. It has a broad spectrum of antineoplastic activity and causes less marked myelosuppression than many other cytotoxic agents. At present, the role of ifosfamide/mesna in refractory germ cell testicular cancer is clearly defined; however, its overall place in the treatment of other forms of cancer awaits delineation in future well-controlled comparative studies.
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PMID:Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. 172 Mar 82

In an ongoing phase II trial conducted in advanced breast cancer, we tested a therapy schedule consisting of continuous, 24-h infusion of 5 g/m2 ifosfamide (IFO) in 3 1 dextrose saline with mesna (MSN), repeated every 3 weeks until disease progression. Since September 1988, 16 heavily pretreated patients with advanced disease (11 with visceral lesions) considered refractory to standard chemotherapy (regimens always including cyclophosphamide) have been included. Objective partial remissions were observed in two cases (one in liver and one in soft-tissue and pleural lesions), and disease stabilization for at least 3 months occurred in four cases. No treatment-related death was recorded and tolerance was judged to be excellent (six cases) or acceptable in all instances. The haematological toxicity consisted mainly of transient leucopenia (nadirs evaluated by WHO scale as grade 3 in 43% and grade 4 in 29%), sometimes associated with thrombocytopenia (grade 3 in 7% and grade 4 in 7%). Other side effects included nausea and/or vomiting (grade 3-4 in 33%); worsening of preexisting alopecia (five cases); haemorrhagic cystitis (one case); mild, transient somnolence (two cases); and moderate fluid retention (two cases). We concluded that infusion of 5 g/m2 IFO over 24 h with MSN rescue might represent an acceptable second- or third-line salvage regimen. Close monitoring of haematological and renal function parameters is recommended. A larger number of patients will be treated in a continuation of this study to evaluate the true response rate within narrower confidence limits.
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PMID:Experience of the Belgian Society of Medical Oncology with single-administration 5 g/m2 ifosfamide with mesna as second- or third-line therapy in advanced breast cancer. 211 55

Nineteen women receiving their first cycle of adjuvant chemotherapy for early breast cancer were randomized between two antiemetic drugs: methylprednisolone (MPN) 125mg and metoclopramide (MCP) 20mg, both given by intravenous push as a single dose. The chemotherapy included: cyclophosphamide, methotrexate and 5-fluorouracil (CMF). The total response rates for MPN and MCP were: complete protection 11% versus 0% and partial protection 63% versus 11% of the patients, respectively (P = 0.007). Eighteen patients (95%) preferred MPN over MCP. Common side effects with both drugs were: drowsiness, headache and diarrhea. MPN is recommended as an antiemetic in patients receiving CMF adjuvant chemotherapy.
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PMID:Methylprednisolone versus metoclopramide as antiemetic treatment in patients receiving adjuvant cyclophosphamide, methotrexate, 5-fluorouracil (CMF) chemotherapy: a randomized crossover blind study. 269 21

One hundred and one postmenopausal patients with advanced breast cancer were enrolled in a randomized phase II clinical trial to investigate the clinical and hormonal response to aminoglutethimide administered at daily doses of 2 x 125 mg, 3 x 125 mg or 2 x 250 mg, with no addition of hydrocortisone. Among 71 evaluable patients 25% showed objective tumor response (three complete, 15 partial), at all three dose levels and irrespective of the major tumor site. Previous treatment with Tamoxifen had been successful in 75%. Out of the 18 responding patients 10 had estrogen receptor positive, four had estrogen receptor negative tumors; the receptor status was unknown in four other patients. Progression-free interval was more than 700 days in 50% of the responders. Drowsiness caused early drug withdrawal in one patient. Side-effects were very mild, comparing favorably with standard therapy of 250 mg aminoglutethimide q.i.d. plus hydrocortisone. Plasma estrogen levels were reduced by all doses to the same 50% or less as in patients on standard treatment. In nine out of 27 patients a further decrease of estrone levels could be monitored with clinically improved results in five. Plasma cortisol and mineralocorticoids remained normal throughout more than 6 months. The original role of hydrocortisone administration to suppress a reflex rise of ATH in 'medical adrenalectomy' with standard dose aminoglutethimide is no longer tenable. Further phase III comparative clinical results pending, low dose aminoglutethimide as an aromatase inhibitor may at present be considered as an appropriate second-line endocrine treatment with low toxicity and expense.
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PMID:Low dose aminoglutethimide without hydrocortisone for the treatment of advanced postmenopausal breast cancer. 270 89

Low dose aminoglutethimide 125 mg twice daily plus hydrocortisone 20 mg twice daily was shown to produce oestrogen and androgen suppression in postmenopausal women. A phase II study was carried out in 101 patients with advanced postmenopausal breast cancer. Objective response rates were 4% CR and 21% PR. Fourteen per cent had disease stabilization for more than 6 months (SD). Soft tissue sites showed the best response. Responses occurred in previous tamoxifen failures (28%) including SD. Toxicity was less than reported for higher dose regimens or low dose aminoglutethimide without hydrocortisone, particularly nausea and drowsiness. Survival from first relapse and start of therapy was not significantly different between PR and SD. This dosage regimen appears of comparable efficacy to previously reported higher dosage regimens with reduced toxicity compared to low dose regimens without hydrocortisone.
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PMID:Phase II study of low dose aminoglutethimide 250 mg/day plus hydrocortisone in advanced postmenopausal breast cancer. 275 65

In an attempt to define the activity and toxicity of low-dose aminoglutethimide plus steroid replacement in advanced breast cancer, we treated 40 patients with aminoglutethimide 500 mg/day + hydrocortisone 50 mg/day. Previous treatment consisted of additive hormones in 29 patients, oophorectomy in 8, and chemotherapy in 32. Among the 37 patients evaluable for response and toxicity, 5 objective responses (16.2%) and 20 stable diseases (54%) were noted. Toxicity, absent in 23 patients (62.1%) and mild in 14, consisted mainly of Grade I (WHO) nausea, drowsiness, cutaneous rash, and dizziness. Responders and patients with stable disease experienced a similar survival (median not reached at 22 months). Aminoglutethimide at low doses appears to be beneficial in patients refractory to conventional therapies even if the objective response rate is low.
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PMID:Low-dose aminoglutethimide plus steroid replacement in advanced breast cancer patients resistant to conventional therapies. 279 May 34

From July 1980 to June 1983, 61 postmenopausal women with progressive metastatic breast cancer were treated with aminoglutethimide, 250 mg 4 times daily, plus cortisone acetate, 25 mg twice daily. Of 51 evaluable patients, an objective remission was observed in 22 (43%) (partial remission in 19, complete in 3), stable disease in 14 (27%), and progressive disease in 15 (30%). The median duration of response was 60 weeks (range 12+; 94+). The response rate was higher when the dominant disease site was soft tissue (50%) or bone (56%) rather than viscera (29%). Side effects were common but usually slight and transient. Somnolence (69%), dizziness (41%), nausea (35%) and skin rash (27%) were the most frequent. Serum levels of gamma-GT, alkaline phosphatase and total cholesterol rose during aminoglutethimide treatment, whereas levels of uric acid and indirect bilirubin decreased. Aminoglutethimide plus cortisone acetate appears to be an active and relatively safe treatment in advanced breast cancer and may be recommended as second-line endocrine treatment.
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PMID:Aminoglutethimide in advanced breast cancer. 286 33

A phase I-II study of human recombinant interferon gamma (rIFN-gamma) was conducted in patients with various advanced cancer refractory to standard chemotherapies. In the phase I study, seven patients received 14 courses of escalating doses ranging from 2 X 10(6)U/m2 to 64 X 10(6)U/m2 by 1-hour intravenous infusion for 5 consecutive days. The toxicities were high fever with chills, anorexia, occasional nausea and vomiting, elevation of serum GOT, and dose-related leukopenia and neurotoxic symptoms such as heavy fatigue with somnolence or lethargy, both of which were reversible. The pharmacokinetics showed that the peak levels of serum rIFN-gamma activity were dose-related but decreased rapidly to below measurable levels within 6 hours after infusion in patients receiving less than 12 X 10(6)U/m2. Considering these data, the dosage of rIFN-gamma 6 X 10(6) U/m2 by daily intramuscular injection for more than 4 weeks was selected for the early phase II study. There was no partial response out of 11 evaluable patients but a stable condition was observed in 2 cases of renal cell carcinoma and one case each of breast cancer and ovarian cancer. All toxicities seen were similar to those observed in the phase I study, but no tachyphylaxis developed with continued dosage. The antitumor effect of rIFN-gamma remains to be evaluated in a further study employing higher doses.
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PMID:[Phase I-II study of recombinant interferon gamma]. 298 59

Administration of orimeten (aminoglutethimide), for disseminated breast cancer in 38 postmenopausal females, in whom other treatment modalities had failed, proved effective in 39%. Patients who had failed on tamoxifen responded to orimeten. Such side-effects as skin rash, drowsiness and cardiovascular disturbances were not pronounced. Limiting toxicity was 6%.
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PMID:[The use of aminoglutethimide (orimeten) in disseminated breast cancer]. 359 Jun 72


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