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)

In the dose finding study we were able to demonstrate that an increase of the epirubicin dose to 120 mg/m2 in combination with cyclophosphamide (600 mg/m2) is possible. The phase II trial had to check the efficacy and the toxicity of this combination with a therapy interval of 21 days. 34 patients with metastatic breast cancer previously not treated with chemotherapy for metastatic disease entered this phase II trial, which tested the efficacy and toxicity of the chemotherapy combination epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 (HD-EC regimen) i.v. every three weeks. Excluded from the trial were patients at risk of anthracycline toxicity and those with bone or brain metastases. Results compare favourably with best data reported in the literature for chemotherapy of metastatic breast cancer: overall remission rates of 73% (35% CR, 38% PR), median TTP of 58 weeks for CR (range 32-168 weeks) and 52 weeks for the PR group (range 24-110 weeks); median survival time for CR 71+ weeks (range 52-196+), for PR 74+ weeks (range 40-134+ weeks). No therapy was given for remission maintenance after a stable remission was obtained. This results in a very favourable ratio of time with chemotherapy to maintenance time without chemotherapy, which is 10 weeks/62 weeks for CR and 12 weeks/49 weeks for PR. Evidence of tumor remission was found in 80% of the patients who already responded to chemotherapy after the first cycle. The early onset of tumor response as well as the short induction chemotherapy period necessary to obtain best response are considered major advantages of the HD-EC regimen.
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PMID:High-dose epirubicin in combination with cyclophosphamide (HD-EC) in advanced breast cancer: final results of a dose finding study and phase II trial. 223 80

The traditional hormonal cascade of the 1970s and 1980s used tamoxifen followed by megestrol acetate and subsequently by aminoglutethimide. In the 1990s, however, three trials of third-generation aromatase inhibitors (AIs) compared with megestrol acetate and two trials of third-generation AIs compared with aminoglutethimide showed improved efficacy and decreased toxicity for the newer AIs. Thus, the hormonal cascade changed in the late 1990s, to one in which tamoxifen, followed by a third-generation AI, followed by megestrol acetate, seemed more suitable. Now, however, several trials comparing anastrozole, letrozole, and exemestane to tamoxifen as first-line hormonal agents for metastatic breast cancer have shown that these drugs are at least equivalent and perhaps superior to tamoxifen in that setting in terms of response rate and time to progression. Results from 1021 patients randomized to receive anastrozole versus tamoxifen showed a slightly improved overall response rate (RR; 29% versus 26%), slightly improved clinical benefit (CB; 57% versus 52%), and a significantly improved time to progression (TTP; 8.5 months versus 7.0 months) in favor of anastrozole. In 907 women randomized to treatment with letrozole versus tamoxifen, significantly improved RR (30% versus 20%), CB (49% versus 38%), and TTP (9.4 months versus 6 months) have all been shown for those treated with letrozole. In addition, a randomized Phase II trial of 121 patients has shown nonsignificant benefits in favor of exemestane (RR 41% versus 14%; CB 56% versus 42%; TTP not available). To date, none of these trials has demonstrated any overall survival benefit. Additional follow-up in regard to survival in the trial of tamoxifen versus letrozole and an expanded Phase III trial of tamoxifen versus exemestane are ongoing.
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PMID:The role of tamoxifen and aromatase inhibitors/inactivators in postmenopausal patients. 1191 25

We performed combined therapy with trastuzumab-vinorelbine for 6 HER2 positive metastatic breast cancer patients from which informed consent was obtained. As the initial dosage, we administered 4 mg/kg of trastuzumab, followed by a dosage of 2 mg/kg every week thereafter. At the same time, 25 mg/m2 of vinorelbine was administered for 2 weeks, followed by a week of rest. Total administration frequency of trastuzumab was 13-34 times (median: 27 times) and vinorelbine was 8-22 times (median: 17 times). A partial response was seen in 4 patients and no change in 2, for a response rate of 66%. A fixed period effect was recognized in each case, and the TTP was 112-274 days (median: 205 days). The side effects recognized were leukopenia of grade 3 in 1 patient, but she recovered during a withdrawal period. After that, continuous administration was possible. Trastuzumab-vinorelbine combined therapy expanded treatment alternatives for HER2 positive metastatic breast cancer patients and might prolong life.
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PMID:[A pilot study of trastuzumab and vinorelbine-combined therapy for metastatic breast cancer]. 1517 Sep 84

Exemestane is a potent steroidal aromatase inhibitor (AI) with activity in post-menopausal women with metastatic breast cancer, with a reported clinical benefit (CB) rate of 24.3% after prior AI therapy. Data on 114 patients (112 female, 2 male) were obtained retrospectively at two cancer centres. Sixty-five percent of patients were confirmed as oestrogen receptor (ER) positive. All patients had received prior third-generation AI therapy. Responses were seen in 5% and the overall CB rate (CR+PR+SD24 weeks) was 46%. Median PFS and OS were 18 and 61 weeks, respectively. In patients with visceral disease, the CBR was 33%. Patients with known ER-positive disease had a CBR of 47%, and a median TTP of 19 weeks. No benefit was seen in patients with known ER-negative disease. Survival was better in those with CB (median survival not reached in those with CB, 28 weeks in those without CB P<0.0001). Efficacy persisted in those patients who had received 3 prior lines of hormonal therapy, including adjuvant treatment. These data confirm exemestane to be an effective therapy after third-generation non-steroidal AI in post-menopausal ER-positive metastatic breast cancer, including visceral disease.
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PMID:Exemestane in metastatic breast cancer: effective therapy after third-generation non-steroidal aromatase inhibitor failure. 1623 14

The endpoints of confirmed response and progression are widely used in oncology clinical trials. These endpoints originated at a time when agents used to treat cancer were primarily cytotoxic. Increasingly agents that are cytostatic are being investigated in combination with agents that are cytotoxic. Since tumor growth rates often depend on the volume of the tumor, combining cytotoxic agents that reduce tumor volume with cytostatic agents may mask the activity of the cytostatic agent. This paper explores the sensitivity of time to progression/progression free survival (TTP/PFS) as an endpoint for evaluating the efficacy of cytostatic drugs when combined with cytotoxic agents. Mathematical models of tumor growth are used to describe tumor growth over time. The models account for the impact of chemotherapy and an agent that slows tumor growth in the context of the Gompertzian growth kinetics. We use a clinical trial of an angiogenesis inhibitor in metastatic breast cancer as a motivating example. We demonstrate that the endpoint TTP/PFS may not be sensitive to the effects of active cytostatic agents when they are combined with chemotherapy, and measuring time to regrowth would be more sensitive to the activity of a cytostatic agent. We conclude that an active cytostatic agent may not appear effective when combined with chemotherapy and evaluated with TTP/PFS in a clinical trial.
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PMID:Endpoints for agents that slow tumor growth. 1744 34

A phase II trial was performed to investigate the efficacy and tolerance of combined gemcitabine and liposomal doxorubicin +/- recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with chemotherapeutically pretreated metastatic breast cancer. Thirty-four patients were entered in this trial. Chemotherapy consisted of gemcitabine and liposomal doxorubicin +/- G-CSF. Twenty seven patients received this regimen as 2nd line therapy, five patients as 3rd line and two patients as 4th line therapy after having failed taxane- and/or anthracycline-based chemotherapy or other drug combinations. After a median of six courses, an overall response rate of 26% (9 PR in 34 enrolled patients) was observed; 14 patients had disease stabilization (41%), and eight (24%) progressed. Three patients were not evaluable for response due to anaphylaxis after the first course and protracted thrombocytopenia. The median TTP was 7.5 months, and median overall survival was 15 months. Myelosuppression was the most frequently observed toxicity. Non-haematological side effects were generally mild to moderate. Our data suggest that gemcitabine and liposomal doxorubicin +/- G-CSF is an effective and fairly well tolerated regimen for chemotherapeutically pretreated patients with advanced breast cancer.
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PMID:Phase II trial of pegylated liposomal doxorubicin (Caelyx) plus Gemcitabine in chemotherapeutically pretreated patients with advanced breast cancer. 1745 71

The established clinical activity of docetaxel and ifosfamide as single agents in anthracycline pre-treated breast cancer, led us to conduct a phase I-II study to define the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and clinical activity of the docetaxel+ifosfamide combination in this setting. Patients with histologically confirmed metastatic breast cancer, after failure on prior anthracycline-based chemotherapy, were treated at successive dose levels (DLs) in cohorts of 3-6 with escalated doses of docetaxel 70-100 mg/m(2) over 1 h on day 1 followed by ifosfamide 5-6 g/m(2) divided over days 1+2 (2.5-3.0 g/m(2)/day over 1 h), every 21 days. G-CSF was added once dose-limiting neutropenia was encountered at a certain DL and planned to be incorporated prophylactically in subsequent higher DLs. Between March 1997 and December 2002, 65 patients with a median age of 57 years (range, 32-72) and performance status (WHO) of 1 (range, 0-2) were treated at 5 DLs as follows; 21 in phase I DLs (DL1: 3, DL2: 6, DL3: 3, DL4: 6, and DL5: 3) and the remaining 44 were treated at DL4 (total of 50 patients at DL4), which was defined as the level for phase II testing. All patients were assessable for toxicity and 62 for response. DLT (with the addition of G-CSF after DL2) was reached at DL5 with 2/3 initial patients developing febrile neutropenia. Clinical response rates (RRs), on an intention-to-treat basis, in phase II were: 56%; (95% CI, 42.2-69.7%); 4 CRs, 24 PRs, 10 SD and 12 PD. The median response duration was 7 mo (3-24 mo), median TTP 6.5 mo (0.1-26 mo), and median OS 13 mo (0.1-33 mo). Grade 3/4 toxicities included: neutropenia in 72% of patients, with 60% developing grade 4 neutropenia (<or=7 days) and in 10% of these febrile neutropenia, while no grade 3/4 thrombocytopenia was observed. Other toxicities included peripheral neuropathy grade 2 only in 10%, grade 1/2 reversible CNS toxicity in 16%, no renal toxicity, grade 2 myalgias in 8%, grade 3 diarrhea in 8%, skin/nail toxicity in 14%, and grade 2 fluid retention in 2% of patients. One patient in the study treated at phase II died as a result of acute liver failure after the first cycle. The present phase I-II study has determined the feasibility, defined the MTD and demonstrated the encouraging activity of the docetaxel-ifosfamide combination in the phase II part of the study. Therefore, future randomized phase III studies versus single-agent docetaxel or combinations of the latter with other active agents are warranted.
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PMID:Docetaxel-ifosfamide combination in patients with advanced breast cancer failing prior anthracycline-based regimens: results of a phase I-II study. 1759 29

Background Endoglin (CD105) is a co-receptor for TGF-beta, is expressed by human vascular endothelial cells, and plays a major role in angiogenesis. Materials and methods Pretreatment EDTA plasma from 224 metastatic breast cancer patients enrolled in a phase III 2nd-line hormone therapy trial and 50 control subjects were assayed for endoglin using an ELISA. Results The female control group (n = 50) plasma endoglin upper limit of normal was defined as the mean + 2 SD (8.7 ng/ml). The breast cancer patient plasma endoglin was 6.40 +/- 2.23 ng/ml (range 3.00-19.79 ng/ml). Elevated plasma endoglin levels were detected in 26 of 224 patients (11.6%). Patients with elevated plasma endoglin had a reduced clinical benefit rate (CR + PR + Stable) (15 vs. 42%) (P = 0.01) to hormone therapy. TTP was shorter for patients with elevated plasma endoglin, but did not reach statistical significance (P = 0.2). Patients with elevated plasma endoglin had decreased overall survival (median 645 vs. 947 days) (P = 0.005). Conclusion Elevated pretreatment plasma endoglin levels predicted for decreased clinical benefit and a shorter overall survival in metastatic breast cancer patients treated with 2nd-line hormone therapy.
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PMID:Elevated plasma endoglin (CD105) predicts decreased response and survival in a metastatic breast cancer trial of hormone therapy. 1911 6

The prognostic value associated with the detection of circulating tumor cells (CTCs) in metastatic breast cancer by the CellSearch technology raise additional issues regarding the biological value of this information. We postulated that a drug-resistance profile of CTCs may predict response to chemotherapy in cancer patients and therefore could be used for patient selection. One hundred 5 patients with diagnosis of carcinoma were enrolled in a prospective trial. CTCs were isolated from peripheral blood, and positive samples were evaluated for the expression of a panel of genes involved in anticancer drugs resistance. The drug-resistance profile was correlated with disease-free survival (DFS; patients in adjuvant setting) and time to progression (TTP; metastatic patients) in a 24-months follow-up. Objective response correlation was a secondary end point. Fifty-one percent of patients were found positive for CTCs while all blood samples from healthy donors were negative. The drug-resistance profile correlates with DFS and TTP (p < 0.001 in both). Sensitivity of the test: able to predict treatment response in 98% of patients. Specificity of the test: 100%; no sample from healthy subject was positive for the presence of CTCs. Positive and negative predictive values were found to be 96.5 and 100%, respectively. We identified a drug-resistance profile of CTCs, which is predictive of response to chemotherapy, independent of tumor type and stage of disease. This approach may represent a first step toward the individualization of chemotherapy in cancer patients.
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PMID:Chemosensitivity profile assay of circulating cancer cells: prognostic and predictive value in epithelial tumors. 1982 89

Vinorelbine (i.v.) plus capecitabine (oral) combination therapy is active in anthracycline/taxane pretreated patients with metastatic breast cancer. Availability of oral vinorelbine provides this combination in an all-oral formulation. Two consecutive phase II trials differing only in vinorelbine administration routes evaluated their respective activities and tolerabilities in this population. In the i.v. group (n = 38) disease control was 61% (37% PR, 24% SD), median TTP 6.8 months and median survival 11.3 months. In the oral group (n = 38) disease control was 77% (5.4% CR, 34% PR, 38% SD), median TTP 7 months and median survival 10 months. G3-G4 neutropenia was more common in the oral group (p < 0.05); G2-G3 anaemia [5] and G3 thrombocytopenia [1] were observed only in the oral group. Although the comparison between the two regimens was not randomized, the results observed in these two consecutive phase II studies may suggest that oral and iv vinorelbine, in combination with capecitabine, can achieve similar responses in patients with metastatic breast cancer refractory to anthra-taxane combinations.
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PMID:Intravenous versus oral vinorelbine plus capecitabine as second-line treatment in advanced breast cancer patients. A retrospective comparison of two consecutive phase II studies. 2016 91


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