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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

5-Fluorouracil plus folinic acid and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) are effective salvage therapies for metastatic breast cancer patients. Paclitaxel and 5-fluorouracil have additive cytotoxicity in MCF-7 cell lines. We performed a phase II trial of paclitaxel 175 mg/m2 over 3 hours on day I followed by folinic acid 300 mg over 1 hour before 5-fluorouracil 350 mg/m2 on days 1 to 3 every 28 days (TFL) in women with metastatic breast cancer. Analysis is reported on 37 patients with a minimum of 6 months follow-up who received a total of 192 cycles of TFL: nine cycles (5%) were associated with grade 3/4 neutropenia requiring hospitalization; seven (4%) cycles in two patients required granulocyte colony-stimulating factor due to neutropenia; no patient required platelet transfusions. Grade 3/4 nonhematologic toxicities were uncommon. Among the 34 patients evaluable for response, there were three complete responses (9%) and 18 partial responses (53%) for an overall response rate of 62%. Of the 19 evaluable patients with prior doxorubicin exposure, 11 (58%) responded compared with nine of 15 (60%) without prior doxorubicin. Plasma paclitaxel concentrations were measured at the completion of paclitaxel infusion and at 24 hours in 19 patients. TFL is an active, well-tolerated regimen in metastatic breast cancer.
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PMID:Paclitaxel, 5-fluorouracil, and folinic acid in metastatic breast cancer: BRE-26, a phase II trial. 907 36

Previous phase II studies of continuous infusion Fluorouracil (5-FU) (CI 5-FU) in refractory metastatic breast cancer have shown modest activity with low toxicity. Its activity in a first-line setting has not been formally tested. Patients were eligible if they fulfilled the following criteria: metastatic breast cancer; measurable or evaluable disease, no prior chemotherapy in the metastatic setting; ECOG performance status of 0, 1, or 2: adequate bone marrow and liver function. Patients were treated with 5-FU 250 mg/m2 per day by continuous intravenous infusion for 5 weeks in a 6-week cycle. Treatment was continued until disease progression or unacceptable toxicity. In addition to the traditional endpoints of response, survival, and toxicity, quality of life was assessed with the Functional Living Index-Cancer (FLIC) and the Symptom Distress Scale (SDS). Twenty-one patients were enrolled. Among the 16 patients with measurable disease, the objective response rate was 44% (95% CI 20%, 68%) with CR rate 13% and PR rate 31%. The median duration of response was 37 weeks. Responses were not observed in patients with visceral (lung or liver) disease. Among all 21 patients in the study, the median time to disease progression was 12 weeks, and median overall survival was 64 weeks. Grade 1 or 2 mucosal and cutaneous toxicity were common. Only 4 patients (19%) had toxicity greater than grade 2; three patients had grade 3 mucositis, and 1 patient developed an indwelling catheter infection requiring its removal. Among responding patients, mean FLIC scores improved from 114.3 at baseline to 128.7 at week 8 (p = 0.11). Symptoms reported on the SDS generally improved in responding patients. Continuous infusion 5-FU as a first-line therapy for metastatic breast cancer has moderate activity and low toxicity. Its use should be considered in the first-line setting when toxicity needs to be minimized.
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PMID:Continuous infusion 5-fluorouracil as first-line therapy for metastatic breast cancer. 922 18

The efficacy of intra-arterial infusion chemotherapy (IACT) as the first step in a combined modality therapy in the treatment of locally advanced breast cancer was evaluated in a prospective clinical study consisting of 18 patients, 15 with stage IIIB, and three with stage IV breast cancer. A combined chemotherapy using adriamycin, mitomycin C and 5-Fluorouracil were administered at 3-week intervals until sufficient regression was achieved. Objective response rate was 66.6%. Among the 14 patients who received IACT for induction, plus surgery, simultaneous adjuvant chemotherapy and radiotherapy, 7 were disease-free at a mean of 19.5 (range 4-42) months. Six patients developed various relapses at a mean of 20.6 (range 12-28) months. IACT was found to be quite effective in local control. The early systemic relapse continues to be a serious problem that needs further intervention.
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PMID:Intra-arterial infusion chemotherapy in the treatment of locally advanced breast cancer. 929 45

During the 1990s, one in nine women in the western world will be diagnosed with breast cancer, and more than 58,000 will die of the disease each year in Europe alone. Recent changes in the primary therapy of operable breast cancer have not altered patient prognosis. Adjuvant therapy delays systemic recurrence and improves survival for only a fairly selected fraction of these patients. Therapy for metastatic breast cancer has not improved significantly in recent years. While combination chemotherapy may prolong survival in selected patients, few if any achieve cure. Standard chemotherapy regimens used to treat metastatic breast cancer, such as CMF (cyclophosphamide/methotrexate/fluorouracil), FAC (5-FU/Adriamycin/cyclophosphamide), and FEC (5-FU/epirubicin/cyclophosphamide), were developed over a decade ago. Current efforts to improve therapeutic efficacy have concentrated on decreasing drug toxicity and increasing drug doses (e.g., high-dose chemotherapy with peripheral stem cell support). An important alternative to increasing therapeutic efficacy by such approaches is altering the administration schedules of well-known chemotherapeutic agents and introducing active new cytotoxic agents. One of the most frequently used cytotoxic drugs, 5-FU has documented activity in a variety of malignancies, most notably in breast cancer and gastrointestinal tract cancers. However, despite broad clinical experience, our knowledge of mechanisms of resistance in relation to various 5-FU schedules is limited. In vitro data and clinical experience show that resistance to one schedule of 5-FU can be overcome by using an alternative schedule, most often a protracted infusion.
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PMID:Metastatic breast cancer: treatment with fluorouracil-based combinations. 934 73

The results from preclinical studies using murine tumor models show that the combination of docetaxel (Taxotere) and fluorouracil (5-FU) is highly synergistic. Phase I studies in patients with advanced solid tumors indicate that 60 mg/m2 of docetaxel administered as a 1-hour intravenous infusion followed by a daily intravenous bolus of 300 mg/m2 of 5-FU on days 1 through 5 is the recommended dose for phase II studies. Preliminary results from another phase I study using a continuous infusion regimen for 5-FU suggest that 85 mg/m2 of docetaxel administered as a 1-hour intravenous infusion followed by continuous infusion of 750 mg/m2 per day of 5-FU on days 1 through 5 may be the recommended dose for phase II studies. As expected, dose-limiting toxicities included neutropenia and mucositis. Ongoing phase I/II and II studies are investigating the combination of docetaxel with continuous infusion of 5-FU in patients with metastatic breast cancer and with cisplatin (Platinol) and continuous infusion of 5-FU, with and without leucovorin, in patients with head and neck cancer. Preliminary results are encouraging and warrant further study.
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PMID:Docetaxel in combination with fluorouracil for advanced solid tumors. 936 44

Although combination chemotherapy regimens may prolong survival for selected patients with metastatic breast cancer, few, if any, are cured. The standard regimens used in treatment, e.g., CMF (cyclophosphamide, methotrexate, and fluorouracil [5-FU]), FAC (5-FU, Adriamycin, and cyclophosphamide), and FEC (5-FU, epirubicin, and cyclophosphamide), were developed over a decade ago. Current efforts to improve therapeutic efficacy have concentrated on decreasing drug toxicity and increasing drug doses (e.g., high-dose chemotherapy with peripheral stem-cell support). An important alternative approach to increasing therapeutic efficacy focuses on altering the administration schedules of well-known chemotherapeutic agents and introducing active new agents. One of the most frequently used cytotoxic drugs, fluorouracil (5-FU), has documented activity in a variety of malignancies, most notably, breast cancer and gastrointestinal tract cancers. However, despite broad clinical experience with 5-FU, our knowledge about the mechanisms of resistance to the various administration schedules used is limited. In vitro data and clinical experience show that resistance to one schedule of 5-FU can be overcome by using alternative schedules, in particular, a protracted infusion. This article discusses our clinical experience with weekly high-dose 24-hour infusions of 5-FU in combination with folinic acid (leucovorin) alone and together with paclitaxel (Taxol) for the treatment of advanced breast cancer.
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PMID:Fluorouracil-based combinations in the treatment of metastatic breast cancer. 951 1

Treatment of anthracycline-resistant metastatic breast cancer with new antineoplastic agents remains a challenge for the next future. The 5-year survival for this disease is only 15%, and hormonal and chemotherapeutic options remain essentially palliative. New treatment drugs or drug combinations are urgently needed to improve the prospects for patients with metastatic breast cancer, particularly for those with disease characteristics indicating a particularly poor prognosis. Taxanes are promising new drugs and have shown encouraging activity in patients with disease resistant to anthracyclines and in patients with visceral metastases, both with a poor prognosis. Paclitaxel (taxol) is applied with a dose of 175 mg/m2 in a 3 hour infusion and docetaxel (taxotere) with a dose of 100 mg/m2 q 3 weeks. Remission rates are expected between 6-30% for taxol and between 29-48% for docetaxel. Highly active in patients with anthracycline-resistant disease appears to be the vinca-alkaloid vinorelbine too. In patients treated with adriamycin objective remissions between 15-33% can be obtained. The long time known 5-fluorouracil comes to the third place of the effective drugs. Continuous infusion or addition of folic acid increases the intracellular efficacy and results in 5-53% objective remissions. In second-line chemotherapy platin-analogues together with etoposide, vincristine and 5-FU achieve partial or complete remissions between 19-37% for cisplatin containing and 5-12 for carboplatin containing combinations. This may eventually play a role especially if three drug combinations containing paclitaxel, epirubicin and vinorelbine will be used, which are reported to result in 20-33% complete response rates and 66% objective response. The indication for other new drugs like tomudex, topoisomerase-I-inhibitor and gemcitabine for anthracycline-resistant breast cancer remains to be established in multicenter studies.
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PMID:[Therapy of anthracycline-resistant metastatic breast carcinoma]. 962 23

The authors report a phase II pilot investigation in the Southwest Oncology Group examining a combination of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) incorporating modulated 5-FU in patients with poor-prognosis stage IV breast cancer. Patients with poor-prognosis stage IV breast cancer were treated with this "neo-FAC" as front-line therapy. The regimen consisted of 5-fluorouracil by continuous ambulatory infusion pump at 200 mg/m2/day for 42 days, repeated at 56-day intervals; doxorubicin at 20 mg/m2/week intravenously to a maximum cumulative total dose (including adjuvant therapy, if any) of 500 mg/m2; cyclophosphamide 60 mg/m2/day taken orally; methotrexate 15 mg/m2/week intravenously beginning 1 week after termination of doxorubicin; and oral prednisone decreasing from 60 mg/day on a tapering schedule for a total of 7 weeks of treatment. Treatment was continued until progression, unacceptable toxicity, or patient refusal. Twenty-four patients were accrued to this study. Of these, two were ineligible, and the remaining 22 were evaluable for response. Ten patients experienced grade 3 toxicity, and six had grade 4. There were no treatment-associated deaths. Best responses were a complete response in one patient (5%) and partial responses in 6, for an overall response rate of 32% (7/22 evaluable patients). Overall survival in five pilot studies in the Southwest Oncology Group in this poor-prognosis population are relatively superimposable. The present regimen, with its relatively poor outcome and the expense and inconvenience of administering chemotherapy by ambulatory infusion pump, will not be pursued further.
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PMID:'Neo-FAC' (5-fluorouracil, doxorubicin, and cyclophosphamide) for poor-prognosis stage IV breast cancer: a Southwest Oncology Group Phase II Study. 1052 Oct 55

From April 1996 through 1998, we treated twelve metastatic breast cancer patients with CPT-11 100 mg/m2 given on day 1, 8, and 15. All patients had received prior chemotherapy including anthracycline, and also another schedule such as MMC-VDS or HDMTX-5-FU. CPT-11 was well tolerated. One CR, two PR, and two long NC were achieved. Grade 3 leukocytopenia occurred in 2 patients. Grade 1 diarrhea occurred in 3 patients. According to the Kaplan-Meier method, the 50% survival was 354 days. In spite of intense prior chemotherapy, the treatment results with CPT-11 were satisfactory for anthracycline resistant metastatic breast cancer.
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PMID:[A pilot study of irinotecan hydrochloride for metastatic breast cancer--efficacy as a salvage therapy]. 1083 41

Capecitabine (Xeloda) is a new, orally administered, enzyme-activated fluoropyrimidine carbamate designed to generate high levels of fluorouracil (5-FU) in tumor cells. Selective tumor activation of 5'-deoxy-5-fluorouridine, the last enzymatic step of a three-enzyme process, is catalyzed by thymidine phosphorylase, a tumor-associated angiogenic growth factor. Since levels of thymidine phosphorylase are often higher in tumors than in surrounding normal tissues, this stepwise process provides tumor selectivity and potentially decreases toxicity to normal tissues. Preclinical studies show that capecitabine has significant activity against a variety of tumor types when used as monotherapy and in combination with other chemotherapeutic agents. Capecitabine is currently approved for the treatment of patients with metastatic breast cancer resistant to paclitaxel (Taxol) and in whom further anthracycline therapy is contraindicated. It has demonstrated efficacy in patients with advanced colorectal carcinoma, and studies are ongoing in other tumor types.
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PMID:Pharmacology and clinical status of capecitabine. 1103 28


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