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

The pharmacokinetics of doxorubicin given according to three different schedules with a similar dose-time intensity have been studied and compared in 16 women with metastatic breast cancer. Six patients were treated with doxorubicin 75 mg/m2 by i.v. bolus repeated every 3 weeks; 5 patients received doxorubicin by 4-day continuous infusion every 3 weeks (4 at 75 mg/m2 and 1 at 60 mg/m2); 5 patients received 25 mg/m2 by i.v. bolus given weekly. Timed blood samples were collected and plasma levels of doxorubicin and its metabolite doxorubicinol were measured by high-performance liquid chromatography with fluorescence detection. Peak plasma concentrations were measured, and areas under the concentration-time curves calculated. Peak plasma levels of doxorubicin were significantly lower with the 4-day infusion than with either of the bolus injections. The 4-day infusion, however, gave significantly greater total exposure to doxorubicin and doxorubicinol, as indicated by area under the concentration-time curve, than weekly or 3-weekly bolus treatment. A single bolus injection of doxorubicin 25 mg/m2 yielded a total exposure to doxorubicin approximately half that achieved with a 75 mg/m2 bolus injection. Over a 3-week period, therefore, total exposure to doxorubicin would be greater with the weekly low-dose schedule than with the 3-weekly administration. We conclude that drug scheduling has significant effects on doxorubicin pharmacokinetics.
Cancer Chemother Pharmacol 1991
PMID:Comparative pharmacokinetics of doxorubicin given by three different schedules with equal dose intensity in patients with breast cancer. 187 47

The aim of the current pilot study was to determine whether placental isoferritin (PLF) can be detected in the serum of patients with metastatic breast cancer. Sera were obtained from breast cancer patients with metastatic disease (n = 100), from breast cancer with no evidence of disease (n = 70) and from healthy female controls (n = 34). PLF and total serum ferritin levels were independently measured using specific monoclonal antibody ELISAs in a double-blind study. It was found that the mean serum PLF levels were significantly elevated only in patients with visceral metastases (lung, liver, brain) compared with the levels of patients with non-visceral metastases (bone, skin) or with healthy controls. Contrary to this, analysis of total serum ferritin levels did not reveal significant differences between these groups. Considering 0-10 units/ml as a PLF negative result, it was found that PLF was negative in 87.5% of healthy controls and in 96% of breast cancer patients with no evidence of disease. In contrast, PLF was positive in 73% of the patients with visceral metastases and in 29.7% of those with non-visceral metastases. The striking difference between visceral and non-visceral metastases is not yet understood. It could result from a difference in the degree of vascularisation or, alternatively, a difference in the cell types and genes expressed by cells metastasizing to visceral or non-visceral organs.
Cancer Lett 1991 Aug
PMID:Monoclonal antibody CM-H-9 detects circulating placental isoferritin in the serum of patients with visceral metastases of breast cancer. 188 72

We assessed the toxicity and efficacy of high-dose chemotherapy consolidation with reinfusion of purged autologous bone marrow in women with metastatic breast cancer responding to a dose-intense outpatient regimen. Thirty women with hormone-unresponsive metastatic breast cancer, previously untreated with adjuvant doxorubicin or with any chemotherapy for metastatic disease, were treated with cyclophosphamide, methotrexate, doxorubicin, fluorouracil, vincristine, and leucovorin for 16 weeks. Twenty-four patients responded to therapy; 8 showed a complete response, and 16 showed a partial response. These patients proceeded to the next phase of the protocol, ie, marrow harvest and treatment with 6000 mg/m2 cyclophosphamide and 800 mg/m2 thiotepa given over 4 days. Harvested marrow was purged with 100 micrograms/mL 4-hydroperoxycyclophosphamide, and all patients engrafted satisfactorily. The predominant side effects were myelosuppressive and gastrointestinal, and there were no deaths from toxic effects. Three of the 16 patients who showed a partial response after the outpatient phase of treatment achieved a complete response after high-dose therapy. The partial response seen in two more patients converted to a complete response at all sites except bone. The median time to disease progression for all patients in this study was 13 months, and the median survival was 22 months. Four of the original 30 patients remained without disease progression a median of 27 months from entry into the study. This study indicates that this dose-intense regimen can be safely administered, even with the use of purged marrow, with an acceptable toxicity profile. This approach results in a high response rate in women with metastatic breast cancer and could form the basis for a regimen to be tested in the high-risk adjuvant setting.
J Natl Cancer Inst 1991 Jul 03
PMID:High-dose chemotherapy with reinfusion of purged autologous bone marrow following dose-intense induction as initial therapy for metastatic breast cancer. 173 80

Twenty-seven women with metastatic breast cancer were treated with doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH) every other week, alternating with 5-fluorouracil (5FU) and high-dose calcium leucovorin, for a 12-week induction regimen, followed by weekly doxorubicin and oral daily cyclophosphamide. Twenty-five women were eligible and evaluable. Of these, complete response occurred in two patients (8%) and partial response in six patients (24%), for a total response rate of 32%. Toxicity was similar to that seen in previous Southwest Oncology Group (SWOG) trials in this patient population. Response rates in this study were inferior, with comparable median survivals to those of previous SWOG studies that are reviewed. Additional, more dose-intensive approaches incorporating newer approaches to the administration of cancer chemotherapeutic agents are planned.
Cancer 1991 Sep 01
PMID:Alternating weekly doxorubicin and 5-fluorouracil/leucovorin followed by weekly doxorubicin and daily cyclophosphamide in stage IV breast cancer. A Southwest Oncology Group study. 191 89

New approaches are needed in the treatment of advanced breast cancer. In vitro studies have shown that recombinant tumor necrosis factor (TNF) is a growth inhibitor for the MCF-7, ZR-75-1, and BT-20 human breast cancer cell lines. Based on these considerations, the Southwest Oncology Group performed a Phase II trial of recombinant TNF (Genentech) (150 micrograms/m2) given by 30-minute intravenous infusion on days 1 to 5 of every other week for 8 weeks. Patients with metastatic breast cancer who had received one prior chemotherapy regimen for advanced disease were eligible. Of the 22 patients who were entered, 3 were ineligible. Nineteen patients who had a performance status of 2 or less could be examined (median age, 53 years). One possible fatal toxic reaction has been seen in a patient who had intracranial bleeding caused by a previously undiagnosed brain metastasis; no other treatment-related deaths have occurred. Toxicity has included nausea, vomiting, fever, chills, myalgia, and fatigue. No Grade 4 toxicity has been observed. Grade 3 toxic reactions have included hypotension (two patients), diarrhea (one patient), transient leukopenia (two patients), and reversible elevations of liver function test values (two patients). No objective responses have been observed. Twelve of 19 patients have died (median survival time, 8.5 months). Recombinant TNF is inactive as a single agent in patients with previously treated metastatic breast cancer.
Cancer 1991 Oct 15
PMID:A Southwest Oncology Group phase II Trial of recombinant tumor necrosis factor in metastatic breast cancer. 191 10

Fasting blood samples were collected from 83 patients with histologically proven breast cancer and analysed for plasma glucagon, serum immunoreactive tumour necrosis factor (TNF alpha), insulin, glucose, growth hormone, cortisol and TSH. Samples from patients with known diabetes mellitus or thyroid disease, and those on parenteral nutrition or with evidence of infection were excluded as were patients who had a history of weight loss through dieting or who were anorexic. Fasting plasma glucagon, serum cortisol and immunoreactive TNF alpha concentrations in patients with stage IV breast cancer who had developed weight loss were significantly higher than those in patients with stage IV disease who had not developed weight loss. There were no significant differences in the fasting serum concentrations of insulin, glucose, growth hormone and TSH between the two patient groups. The association between weight loss in stage IV breast cancer and increased concentrations of plasma glucagon, serum cortisol and TNF alpha suggests a possible role for these hormonal factors in the development of cancer cachexia.
 ...
PMID:Hormonal factors associated with weight loss in patients with advanced breast cancer. 195 51

Etoposide, despite extensive use in other malignancies, has played a minor role in the treatment of patients with breast cancer. Single-agent trials in which etoposide is administered to heavily pretreated patients with metastatic breast cancer have demonstrated a low overall response rate (6.6% of 383 patients), with no convincing evidence for either schedule dependence or a relationship between dose intensity and response. The sole single-agent trial in previously untreated patients suggested that the drug has an approximately 15% response rate in untreated patients. Combination therapy trials in which etoposide has been combined with either cyclophosphamide, doxorubicin, or cisplatin have not yet convincingly demonstrated superiority over any of these drugs as single agents, although cisplatin plus etoposide appears to be superior to either agent alone. In vitro studies suggest that pretreating hormone-sensitive breast cancer cells with estradiol may increase their sensitivity to etoposide-induced DNA cleavage. This may represent a future direction in the use of etoposide in breast cancer. Currently, however, the use of etoposide in breast cancer should be considered investigational.
Cancer 1991 Jan 01
PMID:Etoposide in the management of metastatic breast cancer. 198 26

A randomized trial was performed to determine if therapy with tamoxifen (TAM) plus fluoxymesterone (FLU) was more efficacious than TAM alone for postmenopausal women with metastatic breast cancer. Patients failing TAM could subsequently receive FLU. The dose of both drugs was 10 mg orally twice daily. Objective responses were seen in 50 of 119 (42%) TAM patients and 64 of 119 (54%) TAM plus FLU patients (two-sided P = 0.07). Time to disease progression was better for TAM plus FLU (medians: 11.6 versus 6.5 months; Cox model, P = 0.03). Duration of response and survival were similar in the two treatment arms. Among 97 patients with estrogen receptor (ER) of 10 or greater and 65 years of age or older, there were highly significant advantages for treatment with TAM plus FLU in both response rate and time to progression. Of particular note is that in this patient group TAM plus FLU showed a survival advantage (Cox model, P = 0.05). Although these data require confirmation in a prospective randomized trial, they suggest that there is a substantive therapeutic advantage for TAM plus FLU over TAM alone in elderly women with ER of 10 fmol or greater.
Cancer 1991 Feb 15
PMID:Combination hormonal therapy with tamoxifen plus fluoxymesterone versus tamoxifen alone in postmenopausal women with metastatic breast cancer. An updated analysis. 199 Dec 61

A group of 40 women with objectively measurable metastatic breast cancer was treated with idarubicin, 35 mg/m2 on day 1, and cyclophosphamide, 200 mg/m2 on days 2-5, both drugs being administered orally every 3 weeks. Of 37 evaluable patients, 4 (10.8%) achieved a complete response and 14 (37.8%) a partial response, for an overall response rate of 48.6% (95% confidence interval, 37.45%-59.75%). In previously untreated patients the response rate was 58.3%, whereas it was 44% in patients previously exposed to cytotoxic drugs. The median duration of response was 6.5 months, and the median survival of all patients was 10.5 months. Moderate nausea and vomiting were common. Diarrhoea, which occurred in 37% of the patients, was usually short-lived. Alopecia was generally mild, myelosuppression was the dose-limiting toxicity. Grade 3-4 leukopenia occurred only in pretreated patients. In previously untreated patients it was generally of grade 1-2. Laboratory evidence of cardiotoxicity (greater than or equal to 20% decrease in the left-ventricular ejection fraction from the baseline value) was observed in 3 out of 26 patients, who had at least two determinations of the left-ventricular ejection fraction, and was transient in nature. No cases of congestive heart failure were observed. These results indicate that the combination of idarubicin + cyclophosphamide represents a practical and effective regimen to be used in selected patients with advanced breast cancer.
J Cancer Res Clin Oncol 1991
PMID:Combination chemotherapy with oral idarubicin and cyclophosphamide for metastatic breast cancer. 199 73

A total of 40 patients with metastatic breast cancer were treated with 120 mg/m2 i.v. epirubicin every 3 weeks for a maximum of 10 cycles. Nine achieved a complete response and 17 showed a partial response, for an objective response rate of 65% (95% confidence interval, 47%-83%); the median duration of response was 7 months (range, 1-15 months) and median survival amounted to 13 months (range, 2-20 months). Leucopenia (grade 2 or 3) was seen in 14 patients on day 21 of the cycle. A subset of nine patients underwent blood counts on day 10, when all had marked neutropenia (less than 1 x 10(9)/l). Other toxicity was frequent and included nausea/vomiting (80%), alopecia (95%) and stomatitis (35%). Five patients showed a significant fall in cardiac output, but this reverted to normal after treatment. Epirubicin should have a role in the development of high-dose regimens for the treatment of advanced breast cancer.
Cancer Chemother Pharmacol 1991
PMID:High-dose epirubicin as primary chemotherapy in advanced breast carcinoma: a phase II study. 199


<< Previous 1 2 3 4 5 6 7 8 9 10