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)

This prospective study was performed to document the distribution of sites of disease in breast cancer patients with newly diagnosed metastatic disease, and to identify those with assessable or measurable disease by International Union Against Cancer (UICC) criteria. Data were collected on a consecutive series of 100 patients presenting with metastatic breast cancer. Imaging findings recorded included whether patients had assessable or measurable disease and which potentially assessable sites were rendered unassessable by radiotherapy. Radiologically diagnosable complications were recorded. Skeletal metastases comprised the majority, with 67 patients having skeletal involvement, although of these only 33 (49%) had assessable disease and 24 (36%) measurable disease. Sixteen (24%) patients had radiographically occult metastases. Liver ultrasound examination showed metastatic disease in 32 patients, of whom 28 (88%) had measurable lesions and 12% diffuse disease. Chest radiographs demonstrated metastatic disease in 42 patients, with assessable disease in 39 (93%) and measurable disease in 18 (43%). In total, 80 patients had radiologically assessable disease, with five rendered unassessable by the administration of radiotherapy to the only assessable site. Therefore, of the 100 patients, 75% (95% confidence interval (CI) 65-83) had radiologically assessable disease, with 55% (95% 45-65 CI) having measurable lesions by UICC criteria.
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PMID:Imaging of metastatic breast cancer: distribution and radiological assessment at presentation. 1152 92

The efficacy of vinorelbine given as a continuous infusion was evaluated in 47 patients with breast cancer who had received previous treatment with first-line, second-line, and third-line chemotherapy including taxanes and/or anthracyclines. For inclusion into the study, patients were required to have histology-proven bi-dimensionally measurable disease. The treatment schedule was a bolus injection of vinorelbine 8 mg/m(2) administered over 5-10 minutes on day 1 followed by vinorelbine 8 mg/m(2) continuous infusion on days 1-4, every 21 days for 6 cycles. On an intent-to-treat basis, a 2% complete response rate and a 17% partial response rate were observed. The median time to progression was 2.4 months (95% CI, 1.83-2.97). Median survival was 7.73 months (95% CI, 4.48-10.98; range, 0.33-55.0 months). Major toxicities included febrile neutropenia in 40 cycles (24%) affecting 24 patients (51%) and 1 toxic death. Other nonhematologic toxicities included stomatitis (13%) and asthenia (13%). We conclude that this treatment shows considerable therapeutic activity, albeit at considerable toxicity costs, even in patients who have had multiple lines of prior chemotherapy. However, the results do not indicate clear advantages compared to the conventional weekly scheme of administration.
Clin Breast Cancer 2003 Feb
PMID:Vinorelbine as a 96-hour continuous infusion in heavily pretreated patients with metastatic breast cancer: a cooperative study by the GEICAM group. 1263 84

This study was conducted to evaluate the efficacy of high-dose thiotepa, melphalan and carboplatin (TMCb) regimen in 27 patients undergoing autologous stem cell transplantation (ASCT) for metastatic breast cancer. A total of 27 patients with stage IV breast cancer underwent ASCT following thiotepa (500 mg/m(2)), melphalan (100 mg/m(2)) and carboplatin (1200-1350 mg/m(2)). Of 27 patients, 17 had refractory relapse, eight had responding relapse, and two had no evidence of disease (NED) at the time of transplant. In all, 11 patients had only bone disease, nine had bone plus visceral disease, three had only visceral disease, and two had locoregional recurrent disease. The median time from diagnosis to transplant was 1081 days (range 180-2341). Staging for evaluation of response was performed 4-6 months after transplantation. Five patients were not evaluable (NE) for response because of NED at transplant (n=2) or early death due to transplant-related complications (n=3) (two of viral pneumonia and one of regimen-related toxicity) occurring at a median of 4 days (range 11-46) post-transplant. One of the two patients who was NED at the time of transplant is still NED on day 760 post-transplant. Seven of 15 refractory (47%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft-tissue disease with at least improvement in bone lesions. Of 27 patients (37%),(10) are alive and progression-free, a median of 582 days (range 410-1380) after treatment, 6/17 (35%) with refractory disease and 4/10 (40%) with responsive disease. The probability of progression-free survival (PFS) for all patients was 0.50. The probabilities of PFS at 2 years for patients with refractory (n=17) and responsive (n=10) disease were 0.42 and 0.60, respectively. PFS at 2 years for the 14 patients who were NED or achieved CR/PR(*) following-HDC was 0.67. PFS at 2 years for patients who did not achieve CR/PR(*) following-DHC was 0.33. These preliminary data suggest that high-dose TMCb followed by autologous stem cell transplantation is an effective regimen for patients with advanced breast cancer and may be comparable to some previously used regimens.
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PMID:High-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous stem cell transplantation in patients with advanced breast cancer: a retrospective evaluation. 1273 81

Adjuvant chemotherapy in early breast cancer significantly improves disease-free and overall survival. However, a recent update of the world-wide overview indicated that improvements, though statistically significant, are of modest magnitude. Considering the results of individual clinical trials, further improvements in disease-free survival through introduction of new drugs as part of adjuvant treatment for breast cancer are expected to be small. Phase III studies in advanced, measurable disease, each involving several hundreds of patients, have been conducted with both paclitaxel and docetaxel and these results are now available. The high level of efficacy observed, especially with docetaxel, has led to their prompt introduction into adjuvant trials, and the results of one trial with paclitaxel are already available. In this trial, which included 3170 patients, paclitaxel was given every three weeks for four courses following an adjuvant treatment with four courses of doxorubicin and cyclophosphamide (AC) combination. The sequential use of the AC following by the taxane showed an early significant improvement of disease-free survival as compared to AC alone, but the difference observed was exclusively in the 40% of patients who had oestrogen receptor (OR)-negative disease. These patients, and a few of those with OR-positive primaries, did not receive tamoxifen following chemotherapy. Differences in duration of the entire adjuvant treatment programme might have influenced results leading to potentially the wrong conclusion being drawn that the taxane made the difference and other treatment variables had a negligible influence on outcome. Taxanes deserve a 'fair trial' in the adjuvant setting. Moreover, potential cardiotoxicity and long-term impact of high-dose steroids suggest that caution and longer follow-up are required before the definitive introduction of taxanes into the routine care of patients with early breast cancer.
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PMID:Introducing taxanes in the adjuvant treatment of breast cancer: expectations and reality. 1473 36

This study was designed to evaluate the antitumor activity and tolerance of biweekly docetaxel plus vinorelbine as first-line chemotherapy in patients with metastatic breast cancer (MBC). Forty-one patients with measurable disease and no prior chemotherapy for MBC were treated with docetaxel 60 mg/m(2) plus vinorelbine 30 mg/m(2) on day 1, every 2 weeks for a maximum of 12 courses. Median age was 58 years (range, 23-75). Fourteen patients (34.1%) were premenopausal and 27 (65.9%) were postmenopausal. Most patients had received prior neoadjuvant/adjuvant chemotherapy (n = 27, 65.9%), radiation therapy (n = 22, 53.6%), and hormone therapy (n = 21, 51.2%). The most frequent sites of metastasis were bone (n = 18, 43.9%), pleuropulmonary (n = 16, 39%), and liver (n = 14, 34.1%). Twenty-seven patients (65.9%) had more than one site of metastasis. Three hundred and thirty-nine courses were given (median, 8 courses per patient; range, 1-12). Median relative dose intensity was 85% for both docetaxel and vinorelbine. Grade 3/4 toxicities included neutropenia (14 patients, 34.1%), febrile neutropenia (n = 14, 34.1%), and stomatitis (n = 4, 9.8%). No treatment-related deaths were reported. All patients were assessed for response in an intent-to-treat analysis. Four patients (9.8%) had a complete response and 19 (46.3%) had a partial response (overall response rate, 56.1%; 95% CI, 42%-70%). Six patients (14.6%) had stable disease and 12 patients (29.3%) had progressive disease. With a median follow-up of 15.1 months or until death, median duration of response is 12.6 months. Median time to progression is 12.4 months. Median survival time is 19.6 months. This biweekly combination of docetaxel plus vinorelbine is feasible and active as first-line chemotherapy in patients with MBC. This regimen is safe and well tolerated.
Clin Breast Cancer 2004 Jun
PMID:Biweekly docetaxel and vinorelbine as first-line chemotherapy in metastatic breast cancer. 1524 17

Thirty-five patients with metastatic breast cancer (MBC) entered a phase II study of pegylated liposomal doxorubicin 35 mg/m2 intravenously (i.v.) on day 1 plus vinorelbine 30 mg/m2 i.v. on day 1 every 4 weeks. Patients were required to have measurable disease, previous chemotherapy with an anthracycline-containing regimen, and a normal left ventricular ejection fraction (LVEF). Thirty-four patients were assessable for response and toxicity. The overall response rate (on an intent-to-treat basis) was 35% (12 of 34; 95% CI, 20%-54%). One complete response and 11 partial responses were noted. In addition, 14 patients (41%) had stable disease of > 4 months duration, and 7 patients (20.5%) had disease progression. The response rates to the combination when it was used as first- and second-line chemotherapy were 31% (4 of 13) and 38% (8 of 21), respectively. Median time to disease progression was 7 months (range, 1-35 months) and median overall survival was 13 months (range, 2 to > 62 months). Neutropenia was the most frequent toxicity (grade 4 in 44% of patients and 19% of cycles), but neutropenic fever was seen in only 3 cases. No septic deaths occurred. Nonhematologic grade 3 side effects included skin toxicity (palmar-plantar erythrodysesthesia syndrome, 6%) and mucositis (15%). Late alopecia was seen in 53% of patients (grade 1 in 41%, and grade 2 in 12%). The median LVEFs were 64% (range, 50%-81%) at baseline and 62% (range, 37%-70%) after treatment. Three patients presented an LVEF decrease to < 50%; however, no clinical heart failure was noted, and 2 of these patients recovered normal values after cessation of therapy. The combination of pegylated liposomal doxorubicin and vinorelbine can be safely administered to patients with anthracycline-pretreated MBC and is active in this population.
Clin Breast Cancer 2004 Dec
PMID:Phase II study of pegylated liposomal doxorubicin plus vinorelbine in breast cancer with previous anthracycline exposure. 1558 72

The purpose of this study was to define the maximal tolerated dose (MTD), extramedullary toxicities, and pharmacokinetics of docetaxel combined with high-dose melphalan and carboplatin with autologous hematopoietic progenitor cell support. Fifty-nine patients with advanced refractory malignancy (32 breast cancer, 10 non-Hodgkin lymphoma, 6 germ cell tumors, 4 Hodgkin disease, 4 ovarian cancer, 2 sarcoma, and 1 unknown primary adenocarcinoma) with a median of 3 prior chemotherapy regimens and a median of 3 organs involved were enrolled. Treatment included docetaxel (150-550 mg/m2 infused over 2 hours on day -6), melphalan (150-165 mg/m2 infused over 15 minutes from day -5 to -3), and carboplatin (1000-1300 mg/m2 as a 72-hour continuous infusion from day -5). Five patients died from direct regimen-related organ toxicity (2 capillary leak syndrome, 2 enterocolitis, and 1 hepatic toxicity), and 1 additional patient died from pulmonary aspergillosis. The docetaxel MTD was defined as 400 mg/m 2 , combined with melphalan (150 mg/m2 ) and carboplatin (1000 mg/m2 ). The MTD cohort was expanded to enroll a total of 26 patients, 1 of whom died from toxic enterocolitis. The remaining 25 patients presented the following extramedullary toxicity profile, which was manageable and largely reversible: stomatitis, myoarthralgias, peripheral neuropathy, gastrointestinal and cutaneous toxicities, and syndrome of inappropriate antidiuretic hormone secretion. Docetaxel exhibited linear pharmacokinetics in the dose range tested (150-550 mg/m2 ). Pharmacodynamic correlations were noted between the docetaxel area under the curve and peripheral neuropathy or stomatitis. The response rate among 38 patients with measurable disease was 95%, with 47% complete responses. At a median follow-up of 26 months (range, 7-72 months), the 3-year event-free survival and overall survival were 26% and 36%, respectively. In conclusion, a 4-fold dose escalation of docetaxel, combined with melphalan and carboplatin, is feasible with autologous hematopoietic progenitor cell support. The notable activity of this regimen in treatment-refractory patients warrants its further evaluation.
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PMID:Phase I and pharmacokinetic study of docetaxel combined with melphalan and carboplatin, with autologous hematopoietic progenitor cell support, in patients with advanced refractory malignancies. 1581 95

Yondelis (trabectedin, ET-743) is a novel marine-derived anticancer compound found in the ascidian Ecteinascidia turbinata. It is currently under phase II/III development in breast cancer, hormone refractory prostate cancer, sarcomas and ovarian cancer. Activity in breast cancer experimental models has been reported, and preliminary evidence of activity in this setting during the phase I programme has also been observed. The present study assessed the activity and feasibility of trabectedin in women with advanced breast cancer previously treated with conventional therapies. Patients with advanced disease previously treated with at least one but not more than two regimens that included taxanes or anthracyclines as palliative therapy were eligible. Trabectedin 1.5 mg m(-2) was administered as a 24-h continuous infusion every 3 weeks. Patients were kept on therapy until disease progression, unacceptable toxicity or patient refusal. Twenty-seven patients were included between April 1999 and September 2000. Their median age was 54 years (range: 36-67) and 63% of them had two metastatic sites. Twenty-two patients were performance status 1. All patients had previously received anthracyclines, and 23 out of 27 patients had received taxanes. Of 21 patients with measurable disease, three confirmed partial responses, one unconfirmed partial response and two minor responses (49 and 32% tumour shrinkage) were observed; six patients had stable disease. Median survival was 10 months (95% confidence interval: 4.88-15.18). Transient and noncumulative transaminitis was observed in most of the patients. The pharmacokinetic profile of trabectedin in this patient's population is in line with the overall data available with this schedule. The policy of dose adjustments based on the intercycle peaks of bilirubin and alkaline phosphatase appears to have a positive impact in the therapeutic index of trabectedin. Trabectedin can induce response and tumour control in previously treated advanced breast cancer, with manageable toxicity, thus warranting further development as a single agent or in combination regimens.
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PMID:A phase II study of Yondelis (trabectedin, ET-743) as a 24-h continuous intravenous infusion in pretreated advanced breast cancer. 1673 24

Rebeccamycin analog (NSC 655649) is a synthetic antibiotic cytotoxic agent thought to inhibit topoisomerase function. We sought to determine the response rate to rebeccamycin analog among patients with refractory advanced breast cancer using two different treatment schedules. Eligible patients had measurable disease, central venous access, and one or two prior chemotherapy regimens for advanced cancer, or recurrence within 12 months of adjuvant chemotherapy. Patients were randomized to rebeccamycin analog on one of two treatment schedules: arm 1, 500 mg/m2 IV bolus every 21 days; arm 2, 140 mg/m2 IV bolus daily x 5 days, every 21 days. The primary study endpoint was response rate; a two stage accrual design evaluated each schedule separately. Forty-two women entered the trial, 21 on each arm. Prior chemotherapy regimens for metastatic breast cancer were: 0, n=4; 1, n=21; 2, n=17. Prior treatments (including adjuvant therapy) anthracyclines: 88%, taxanes 67%, 5FU-based therapy, 50%. There were 5 partial responses (overall response rate 12%), two in arm 1 and 3 in arm 2, all in patients with prior anthracycline-based adjuvant chemotherapy. Median time to progression was 2.1 months (range 1-14+ months). An additional 9 patients had stable disease as best response. Grade 3 or 4 toxicity rates were: anemia 5%, neutropenia 33%, thrombocytopenia 12%, RBC transfusion 14%, nausea/vomiting 10%. Toxicity profiles were similar between the treatment arms. Rebeccamycin analog is reasonably well tolerated on two different treatment schedules for advanced breast cancer, with modest clinical activity in this heavily pretreated population.
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PMID:Rebeccamycin analog for refractory breast cancer: a randomized phase II trial of dosing schedules. 1696 7

On March 13, 2007, the U.S. Food and Drug Administration approved lapatinib (Tykerb tablets; GlaxoSmithKline, Philadelphia), an oral, small molecule, dual tyrosine kinase inhibitor of ErbB-2 and ErbB-1, for use in combination with capecitabine for the treatment of patients with human epidermal growth factor receptor (HER)-2-overexpressing metastatic breast cancer who had received prior therapy including an anthracycline, a taxane, and trastuzumab. One multicenter, open-label, randomized trial was submitted. Eligible patients had stage IIIb or IV breast cancer, ErbB-2 overexpression (immunohistochemistry 3+ or 2+ with fluorescence in situ hybridization confirmation), measurable disease, a 0 or 1 Eastern Cooperative Oncology Group performance status score, a cardiac ejection fraction within the institutional normal range, and adequate laboratory function. Patients received either lapatinib (1,250 mg once daily on days 1-21) plus capecitabine (1,000 mg/m(2) every 12 hours on days 1-14) every 21 days or capecitabine alone (1,250 mg/m(2) every 12 hours on days 1-14) every 21 days. The primary endpoint was time to progression (TTP) determined by a blinded independent review panel. After TTP results of a prespecified interim analysis were made available, study enrollment was discontinued (399 patients enrolled). The median TTP was 27.1 versus 18.6 weeks (hazard ratio, 0.57; p = .00013) favoring the lapatinib plus capecitabine arm. Response rates were 23.7% (lapatinib plus capecitabine) versus 13.9% (capecitabine alone). Survival data were not mature. Although the toxicities observed in the lapatinib and capecitabine combination arm were generally similar to those in the capecitabine alone arm, a higher incidence of diarrhea and rash was noted with the combination. Grade 3 or 4 adverse reactions that occurred with a frequency of >5% in patients on the combination arm were diarrhea (13%) and palmar-plantar erythrodysesthesia (12%). There was a 2% incidence of reversible decreased left ventricular function in the combination arm.
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PMID:FDA drug approval summary: lapatinib in combination with capecitabine for previously treated metastatic breast cancer that overexpresses HER-2. 1884 20


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