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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Progress in the treatment of breast cancer developed along multiple directions of research during the last decade. The concept of dose-intensity was addressed through retrospective analyses and prospective randomized trials. It was confirmed that dose-intensity correlates with higher response rates, but the effect of dose-intensive treatments on survival still needs to be established. Several new cytotoxic drugs have appeared during the last several years. Taxol, navelbine, and anthrapyrazole CI-941 have been found to have major efficacy against breast cancer, with response rates exceeding 50%. Amonafide, lonidamine, and elliptinium analogs were also shown to be effective, although to a lesser degree. Antiestrogen analogs, new aromatase inhibitors, and LHRH analogs are recent developments that are changing the face of hormonal therapy. Monoclonal antibodies are being developed and evaluated for tumor imaging applications and as vehicles for specific antitumor agents (cytotoxics, radioisotopes, and toxins). Expanding knowledge about the basic biology of breast cancer has led to the identification of growth factors and their receptors, which may be exploited for therapeutic purposes in the not too distant future.
Breast Cancer Res Treat 1992
PMID:Overview of new treatments for breast cancer. 135 16

Taxol, an agent with a unique mechanism of action, has been shown to be highly active in patients with refractory ovarian cancer and may well have significant activity in other malignancies such as breast and lung cancer. The camptothecin analogs, another unique class of agents, have demonstrated antitumor activity in phase I and II trials. Finally, the anthrapyrazoles are intercalating agents with clinical activity in breast cancer and a toxicity profile that may permit increased dose intensity using colony-stimulating factor support. While this review focuses on these three drug classes, a number of other agents with apparently unique mechanisms of antitumor activity and unusual dose-limiting toxicities are in earlier development. These include antimetabolites; inhibitors of DNA, RNA, or protein synthesis; differentiating agents; agents that inhibit tumor growth by binding to growth factors; and agents whose mechanism of action is best classified as unknown.
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PMID:New anticancer agents: taxol, camptothecin analogs, and anthrapyrazoles. 136 58

Tamoxifen is now established for use in premenopausal as well as postmenopausal patients. Recent reports have not shown its activity to be enhanced by the addition of either prednisolone, progestogens, or interferon. Reversible ocular toxicity from tamoxifen appears to be more common than had been previously realized. Different schedules giving the same dose intensity of doxorubicin give markedly different pharmacokinetic profiles. Although this does not lead to differences in responses or physical toxicity, it seems to have important implications for quality of life. Taxol is showing impressive activity in advanced breast cancer, and significant response rates have also been reported for carboplatin and podophyllotoxin derivatives. To achieve maximum effectiveness from the cyclophosphamide, methotrexate, and fluorouracil combination, attention to schedule and dose intensity has been shown to be important. No new effective cytotoxic combinations have been described. High-dose chemotherapy requiring bone marrow support remains experimental. Further progress has been made in monitoring the response of metastatic bone disease to treatment. The precise significance for patients of the results in many of the papers reviewed is often uncertain because they lack quality-of-life measures; the importance of this approach is emphasized.
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PMID:Metastatic breast cancer and its complications. 145 19

The frontline chemotherapy for advanced breast cancer has been either CMF or CAF and the combinations can obtain an overall response rate exceeding 50%, including complete responses of 10-15% and median survival times of 12-18 months. Complete responders have survived longer than patients with partial responses or stable diseases. Consequently, high dose chemotherapy with autologous bone marrow transplantation has been investigated in order to obtain more complete responses and ultimately to obtain a cure in patients responding to induction chemotherapy. Seventeen to 30% of patients who became complete responses have maintained continuously complete responders. Taxol and CI941 are promising agents under investigation.
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PMID:[Chemotherapy of advanced breast cancer]. 160 52

Taxol, an antimicrotubule agent, has shown promise for efficacy in treatment of breast cancer, but severe hypersensitivity reactions led to cessation of many phase I clinical trials. Consequently, investigators and the National Cancer Institute recommended that phase I and II studies of this agent use 24-hour infusions and antiallergic medications. Using a premedication regimen effective in preventing hypersensitivity reactions, we have performed a phase II trial of taxol in patients with metastatic breast cancer. Taxol was administered to 25 patients at a dose of 250 mg/m2 by 24-hour infusion every 21 days. These patients had received only one prior chemotherapy regimen, either adjuvant to surgery or for metastatic disease; all but two had received doxorubicin. In 60% of the patients, the dominant site of disease was the viscera. All patients were assessable. In April 1991, at a median time on study of 9 months (range, 5-13+ months), the objective response rate was 56% (12% complete and 44% partial; 95% confidence interval, 35%-76%). Disease progressed in only 8% of the patients. The median number of courses of therapy was 11. Granulocytopenia was the dose-limiting toxic effect, but neutropenia with fever occurred in only 5% of 232 courses. A chronic glove-and-stocking neuropathy developed in most patients, but no allergic reactions occurred. We conclude that taxol is an active agent in the treatment of metastatic breast cancer and that it warrants continued study. Currently, we are conducting a phase I trial of taxol plus doxorubicin. Future trials should address the optimal effective dose, the optimal sequencing of combinations, mechanisms of drug resistance in tumors, and dose-limiting toxic effects (particularly cardiac toxic effects of taxol given as a single agent or in drug combinations).
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PMID:Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer. 168 8

Taxol is a new anti-cancer drug that is a natural product derived from the bark of the Pacific Yew tree. The drug promotes polymerization and stabilization of tubulin to microtubules and interferes with the mitotic spindle. Clinical trials indicate that taxol is effective in the treatment of patients with refractory ovarian cancer, breast cancer, malignant melanoma and probably other solid tumors. Toxicities include anaphylactoid reactions, leukopenia, peripheral neuropathy and oropharyngeal mucositis. Increased supplies of the drug are required to support further phase II and III testing.
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PMID:Taxol: a new and effective anti-cancer drug. 168 6

Metastatic breast cancer continues to be a challenge for the clinician. Heterogeneity of natural history and drug resistance have interfered with progress in treatment. Hormonal therapy is effective in 30% of patients, some of whom derive long-term benefit from sequential hormonal manipulations. Most patients have hormone-refractory tumors, and eventually all breast cancers become hormone resistant. Cytotoxic chemotherapy is the treatment of choice for these patients. Promising leads in recent clinical investigation include the development of dose-intensive therapies for induction or remission consolidation, biochemical modulation, development of new hormonal and cytotoxic agents, targeted therapy using immunologic or ligand-driven vehicles, and growth factor modulation. Among the encouraging clinical developments, the discovery of the taxanes represents an important step in improving the efficacy of cytotoxic therapy. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) produces objective regressions in 40% to 60% of patients with untreated or minimally treated metastatic breast cancer. The efficacy of this agent persists in patients with chemotherapy-refractory tumors, including those with anthracycline resistance. New paclitaxel-based combinations, especially those with doxorubicin, cisplatin, or vinorelbine, appear promising. This agent, alone or in combination, is also under evaluation in combined-modality strategies for early and advanced primary breast cancer.
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PMID:Management of breast cancer: status and future trends. 748 51

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is the most important new cytotoxic agent to be introduced for the management of breast cancer in many years. During this decade, investigators at Memorial Sloan-Kettering Cancer Center have conducted multiple clinical and laboratory investigations aimed at optimally integrating this agent into therapeutic strategies for breast cancer. These studies address both single-agent and combination regimens in the metastatic and adjuvant settings. This report will review previous results, but focus on active studies and future avenues of research.
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PMID:Memorial Sloan-Kettering Cancer Center experience with paclitaxel in the treatment of breast cancer. 748 52

The addition of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to the therapeutic armamentarium for breast cancer has resulted in novel opportunities and challenges for the clinician. In a series of trials that began in 1992, the Eastern Cooperative Oncology Group (ECOG) investigated the role of paclitaxel in combination with doxorubicin for the treatment of patients with advanced breast cancer. The design of the first trial, a limited-institution pilot study, involved alternating doxorubicin and paclitaxel as single agents. The alternating schedule was well tolerated and associated with objective responses in seven of 12 patients entered into the trial. In the second trial, a limited-institution phase I trial, bolus doxorubicin was combined with paclitaxel administered over a 24-hour infusion, with administration of the two drugs separated by 4 hours. While no dose-limiting toxicity was seen at doses of 50 and 150 mg/m2 of doxorubicin and paclitaxel, respectively, dose-limiting mucositis occurred at respective doses of 60 and 175 mg/m2. Mucositis was more common when administration of paclitaxel preceded that of doxorubicin than when doxorubicin preceded paclitaxel. Based on these results, the ECOG initiated a phase III trial comparing single-agent paclitaxel, single-agent doxorubicin, and the combination of paclitaxel and doxorubicin. This study, now an Intergroup trial of ECOG, the Southwest Oncology Group, and the North Central Cancer Treatment Group, is designed to accrue 730 patients. This trial will close to accrual in September 1995, and analysis of the trial should provide useful information regarding the potential synergy of doxorubicin and paclitaxel, the degree of cross-resistance between the two compounds, and the relationship between steady-state paclitaxel levels and response to therapy. In addition, ECOG is currently conducting a trial designed to confirm the striking activity of cisplatin and paclitaxel seen in the British Columbia trials. Future trials by the group will examine means of combining paclitaxel with other active agents.
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PMID:Doxorubicin/paclitaxel combination chemotherapy for metastatic breast cancer: the Eastern Cooperative Oncology Group experience. 748 54

Twenty-eight patients received Taxol as their first chemotherapy for stage IV breast cancer. An additional 51 patients with extensive prior exposure to other chemotherapeutic agents received Taxol as salvage therapy. We found significant activity for the drug in both situations, as well as a strong clinical suggestion of non-cross-resistance with doxorubicin. An excellent response in previously irradiated skin was noted in one case. The routine use of recombinant human granulocyte-colony stimulating factor seemed to ameliorate some of the dose-limiting toxicity of neutropenia. Other toxicity was mild to moderate in most cases. With further development, Taxol should play a significant role in the systemic management of breast cancer.
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PMID:Taxol plus recombinant human granulocyte-colony stimulating factor as initial and as salvage chemotherapy for metastatic breast cancer: a preliminary report. 751 53


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