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

Oxaliplatin (Eloxatin) has demonstrated significant activity in a variety of tumor types in addition to colorectal cancer. Several studies have reported on the effectiveness of oxaliplatin as single-agent treatment or in combination with cisplatin (Platinol) or paclitaxel (Taxol) in pretreated advanced ovarian cancer patients, with promising data reported for the combination of oxaliplatin and cisplatin as first-line therapy. Other small studies have shown the activity of single-agent oxaliplatin in anthracycline-resistant metastatic breast cancer and refractory non-Hodgkin's lymphoma. Data have also demonstrated the activity of oxaliplatin in combination with gemcitabine (Gemzar) in advanced pancreatic cancer. In recurrent germ-cell cancer, a "biplatin" regimen of oxaliplatin plus cisplatin was found to be effective salvage therapy. Data from these studies indicate that oxaliplatin is active in both platinum-resistant disease and in tumor types that have previously been unresponsive to platinum treatment. Moreover, it enhances the effect of cisplatin or carboplatin, which is a striking demonstration of differing mechanisms of action. Ongoing and planned trials will evaluate the efficacy of oxaliplatin in other disease settings and combinations.
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PMID:Oxaliplatin in tumors other than colorectal cancer. 1120 61

Many active cytotoxic agents exist for breast cancer therapy, and numerous combination chemotherapy regimens are derived from them. Creating these combinations is sometimes empirically motivated by non-overlapping toxicities or the expectation of non-cross resistance. Yet, there is usually no absolute division of these aspects among cytotoxic agents, and the median survival for patients with metastatic breast cancer has not been dramatically prolonged by this approach. When the outcome of treatment is palliation rather than cure, it becomes paramount to optimize the dynamic equilibrium between chemotherapy-induced side effects and the benefits attributable to relief of cancer-related symptoms. To this end, several recent clinical trials have evaluated the novel nucleoside analog gemcitabine (Gemzar) as single-agent therapy for advanced breast cancer. This article reviews these trials.
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PMID:Gemcitabine as single-agent therapy in the management of advanced breast cancer. 1125 82

In a phase II trial, 29 patients with anthracycline-pretreated or anthracycline-resistant metastatic breast cancer in whom anthracycline-containing first- or second-line chemotherapy failed received combination paclitaxel (Taxol)/gemcitabine (Gemzar). The initial regimen of paclitaxel at 175 mg/m2 on day 1 and gemcitabine at 1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle was given to five patients for a total of 27 cycles. The regimen resulted in excessive thrombocytopenia and was subsequently changed to gemcitabine at the same dose on days 1 and 8 of a 21-day cycle, with study treatment being given for a maximum of eight cycles. This regimen was well tolerated. Further evaluation of this regimen in minimally and heavily pretreated patients with advanced breast cancer is warranted.
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PMID:Gemcitabine and paclitaxel as salvage therapy in metastatic breast cancer. 1125 85

Pemetrexed disodium (Alimta, LY231514) is a novel, multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyl transferase. This agent is broadly active in a wide variety of solid tumors, including breast cancer. Pemetrexed disodium has also shown clinically relevant activity in combination with gemcitabine (Gemzar). This combination is being evaluated for the treatment of metastatic breast cancer.
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PMID:Gemcitabine and Pemetrexed disodium in treating breast cancer. 1125 87

A phase II trial evaluated the effectiveness and toxicity of combination paclitaxel (Taxol), gemcitabine (Gemzar), and trastuzumab (Herceptin) as first-line therapy for patients with newly diagnosed HER2-overexpressing metastatic breast cancer. To date, 27 patients have received paclitaxel at 175 mg/m2 over 3 hours on day 1, plus gemcitabine at 1,200 mg/m2 on days 1 and 8, plus trastuzumab at a 4-mg/kg loading dose on day 1, followed by 2 mg/kg weekly. Treatment cycles were repeated every 21 days. Responding or stable patients who had received six cycles of combination therapy continued single-agent trastuzumab weekly until disease progression. Treatment was generally well tolerated with grade 4 toxicity limited to myelosuppression. In all, 12 patients have achieved a partial remission and 1 patient had progressive disease; 14 patients continue treatment and have not yet been evaluated for response. Combination treatment with paclitaxel, gemcitabine, and trastuzumab is well tolerated and appears to be highly active. Accrual will continue to a total enrollment of 46 patients.
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PMID:Gemcitabine, paclitaxel, and trastuzumab in metastatic breast cancer. 1125 88

In a single-center, open, phase II trial, we assessed the toxicity and activity of a triple combination therapy--doxorubicin at 30 mg/m2 (day 1), paclitaxel (Taxol) at 135 mg/m2 (day 2), and gemcitabine (Gemzar) at 2,500 mg/m2 (day 2 after paclitaxel)--administered biweekly in a 28-day cycle for six cycles. This was given as first-line treatment in 41 patients with metastatic breast cancer. Granulocyte colony-stimulating factor was used in 27 patients to permit maintenance of dose density. Hematologic toxicity was moderate. Nonhematologic adverse events were generally mild. The objective response rate was 82.9% (34/41) with 18 patients (43.9%) achieving complete response and 16 (38%) achieving partial response; progressive disease was observed in 4 patients (9.8%). Responses were observed at all metastatic sites, including complete responses in lung, liver, bone, and soft tissue. Median duration of response was 14.1 months and median time to progression was 13.9 months. Median survival was 26.2 months. The biweekly combination of gemcitabine, doxorubicin, and paclitaxel is safe and highly active as first-line treatment in metastatic breast cancer.
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PMID:Biweekly gemcitabine, doxorubicin, and paclitaxel as first-line treatment in metastatic breast cancer. Final results from a phase II trial. 1125 90

Strategies to improve outcome in metastatic breast cancer include the first-line use of combinations of optimal doses of active agents, with the goal being to improve complete response rates and thus long-term survival. Although prior studies of anthracycline/taxane combinations generally have shown improved response rates and progression-free survival in comparison with single-agent regimens or anthracycline/cyclophosphamide-containing combinations, the data have not consistently demonstrated improved overall survival; indeed, they have yielded generally disappointing complete response rates. We evaluated the combination of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), epirubicin, and paclitaxel (GET) based on the hypothesis that epirubicin/paclitaxel is best suited for achieving delivery of optimal doses, and the addition of gemcitabine (which exhibits good single-agent activity with a favorable toxicity profile) will increase activity. In a phase II trial of 36 patients, the GET regimen produced reasonable toxicity and was associated with a 92% response rate, including complete responses in 31% of patients. The overall response rate increased to 97%, including complete responses in 41% of patients, with high-dose consolidation chemotherapy in 25 patients. A trial comparing GET with epirubicin/paclitaxel as first-line treatment in more than 600 patients with metastatic breast cancer has been initiated, with survival as the primary end point. Another large-scale trial is being planned to compare the GET regimen with an anthracycline/cyclophosphamide/paclitaxel combination in patients with early stage high-risk breast cancer. Semin Oncol 28 (suppl 7):15-17.
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PMID:Gemcitabine, epirubicin, and paclitaxel combinations in advanced breast cancer. 1137 47

Several trials have shown that anthracyclines and taxanes can be combined to achieve response rates ranging from 70% to 90%, with complete responses ranging from 19% to 41%. In an attempt to increase the activity while maintaining tolerability, gemcitabine (Gemzar) was added to the epirubicin (Ellence)/paclitaxel (Taxol) regimen. Among 36 metastatic breast cancer patients treated with this new combination, the overall response rate was 92%, including 31% with a complete response. Another attempt to improve the outcome of metastatic breast cancer patients involves a phase III multicentric randomized trial (MANTA-1) to evaluate if paclitaxel maintenance therapy after anthracycline/taxane combination therapy can improve time to progression and overall survival. Although anthracyclines are more frequently used in the adjuvant setting, it is important for the clinicians to know whether this class of drugs can be used again for those patients who develop metastatic disease. An analysis of 312 patients treated with epirubicin containing regimens as first-line treatment for metastatic disease shows that epirubicin-based regimens are active in patients already exposed to anthracyclines in the adjuvant setting, and that the risk of cardiac toxicity is low up to a cumulative epirubicin dose of 990 mg/m2.
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PMID:New combinations with epirubicin in advanced breast cancer. 1139 61

We sought to define the recommended dose of cyclophosphamide (CTX) for subsequent phase II assessment when combined with fixed doses of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and 5-fluorouracil/folinic acid in metastatic breast cancer patients previously treated with anthracyclines and taxanes. Patients age 70 or less, with an Eastern Cooperative Oncology Group performance status 0 to 2, were enrolled. Patients received gemcitabine 1,000 mg/m(2), 5-fluorouracil 425 mg/m(2), folinic acid 100 mg/m(2), and escalating doses of CTX (in 100-mg/m(2) increments), starting at 500 mg/m(2), on days 1 and 8 every 3 weeks. Since March 1999, 46 patients, with a median age of 51 years (range, 38 to 74 years), entered the trial in seven cohorts. Cyclophosphamide dose escalation was stopped at 600 mg/m(2) when three of six patients experienced dose-limiting toxicity (one each with grade 3 thrombocytopenia, grade 3 neutropenia, and persistent grade 2 neutropenia), and then continued with granulocyte colony-stimulating factor support. The CTX dose of 800 mg/m(2) was proven safe and was chosen for phase II study. Two complete and 15 partial responses provided an overall response rate of 37% (95% confidence interval, 23% to 51%). Gemcitabine/CTX/5-fluorouracil/folinic acid is well tolerated by metastatic breast cancer patients pretreated with anthracyclines/taxanes, up to a CTX dose of 800 mg/m(2). The phase II study is ongoing. Semin Oncol 28 (suppl 10):50-56.
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PMID:Gemcitabine/cyclophosphamide/5-fluorouracil/folinic acid triplet combination in anthracycline- and taxane-refractory breast cancer patients: a Southern Italy Cooperative Oncology Group phase I/II study. 1151 34

Docetaxel (Taxotere) has been intensively investigated for the treatment of metastatic breast cancer, where it has proved to be one of the most active agents. Initial phase II studies in anthracycline-resistant metastatic breast cancer demonstrated impressive response rates that have been confirmed in phase III randomized trials. Docetaxel remains the only single agent to demonstrate a survival benefit in anthracycline-resistant patients. More recently, the combination of docetaxel with capecitabine (Xeloda) has demonstrated additional improvement in survival over docetaxel alone in a randomized phase III trial. In patients previously treated with an alkylating agent, docetaxel is the only single drug to demonstrate improved efficacy over doxorubicin in a randomized trial. Docetaxel has been investigated in combination with the anthracyclines doxorubicin and epirubicin in randomized trials. The docetaxel-containing regimens have consistently demonstrated improvement over the non-docetaxel-containing regimens. The efficacy and safety of weekly docetaxel has extended the line of investigation for combinations with agents normally administered on a weekly basis, such as vinorelbine [Navelbine], gemcitabine [Gemzar], and trastuzumab [Herceptin], with promising findings. In addition, the results of the triple-drug combination of docetaxel, a platinum salt (cisplatin or carboplatin), and trastuzumab have resulted in impressive response rates and time to progression in a population of metastatic breast cancer patients with HER2/neu-positive tumors. The consistent demonstration of a high level of efficacy with manageable toxicity ensures the continued widespread investigation of docetaxel in metastatic breast cancer.
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PMID:The current status of docetaxel for metastatic breast cancer. 1210 94


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