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)

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

Capecitabine (Xeloda, Roche, Monza), a fluoropyrimidine carbamate, is an orally administered drug that delivers fluorouracil (5-FU) selectively to the tumor. The drug has demonstrated activity in metastatic breast cancer, pancreatic cancer and colorectal cancer. In this case report the authors describe an unusually and reversible cardiac side effect which occurs to 39-year-old patient treated with capecitabine 2000 mg/m2/day for advanced gastric cancer. It is important to note that the safety data from clinical trials indicate that capecitabine has a toxicity profile typical of infused fluoropyrimidines. However, none of the studies described cardiac side effects.
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PMID:Acute cardiotoxicity during capecitabine treatment: a case report. 1150 78

The efficacy of gemcitabine containing regimens has been explored in a large number of studies presented at ASCO 2002. The activity of gemcitabine-platinum based combinations was confirmed in lung cancer and bladder cancer. In pancreatic cancer, single agent gemcitabine remains the reference treatment, but newer combinations with oxaliplatin or docetaxel show promising activity in phase II trials and are currently being evaluated in phase III. Gemcitabine has demonstrated promising activity in phase II studies in metastatic breast cancer and gynaecologic tumors; phase III trials are ongoing. Concomitant chemo-radiation using gemcitabine as a radiosensitizer have been shown to be highly effective in pancreatic and in bladder cancer and deserve further investigation. The growing interest in gemcitabine-based combinations in various tumor types together with the results presented at ASCO 2002 confirm the broad range of activity of this drug. This is a review of papers presented at ASCO 2002.
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PMID:[Updates on gemcitabine at the American Society of Clinical Oncology congress (ASCO, 2002) ]. 1244 45

Bevacizumab (Avastin) has unprecedented survival benefit in patients with metastatic colorectal cancer. Trials are already in progress to investigate the potential of bevacizumab in indications including metastatic renal cell cancer (RCC), non-small cell lung cancer (NSCLC), pancreatic cancer, breast and ovarian cancer. Bevacizumab offers the potential to increase survival without substantially altering the toxicity profile in these tumor types. Bevacizumab has shown activity in patients with refractory metastatic RCC, where progression-free survival (PFS) was significantly longer in patients treated with bevacizumab (10 mg/kg every 2 weeks) than those treated with placebo (hazard ratio=2.55, p<0.001). In addition, combining bevacizumab with erlotinib (Tarceva) has shown a median time to progression of more than 11 months. In NSCLC, a phase II trial revealed that adding bevacizumab to chemotherapy increased therapeutic benefit compared with chemotherapy alone. Adverse events were mild and easily managed, but six patients receiving bevacizumab developed severe hemoptysis. Entry criteria for NSCLC trials have been adjusted to exclude patients with squamous cell histology to try to avoid this issue. Adding bevacizumab (10 mg/kg) to the current standard of care, gemcitabine, in stage IV pancreatic cancer has also shown promising efficacy. Partial responses were seen in 19% of patients, with a further 48% having stable disease. Several ongoing clinical trials are also studying bevacizumab with various chemotherapy and radiotherapy regimens. Bevacizumab combined with carboplatin (Paraplatin)/paclitaxel (Taxol) was further examined in a phase III randomized trial that accrued 878 patients with advanced non-squamous cell NSCLC. Patients given chemotherapy (paclitaxel and carboplatin) plus bevacizumab had a higher response rate, longer PFS and an increase in survival compared with patients on chemotherapy alone. Both regimens were generally well tolerated. Bevacizumab has also shown activity in patients with metastatic breast cancer. In 715 patients, a significant, 2-fold increase in response rate was observed in patients receiving bevacizumab plus paclitaxel compared with paclitaxel alone. Median PFS was also significantly increased (p<0.001). Bevacizumab has the potential to provide significant efficacy benefits for patients with metastatic RCC, NSCLC, pancreatic cancer, and other tumor types when used first line in combination with standard therapy.
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PMID:Investigating the potential of bevacizumab in other indications: metastatic renal cell, non-small cell lung, pancreatic and breast cancer. 1630 35

We reviewed our clinical trial using mutant herpes simplex virus "HF10". We have evaluated the safety and effect of HF10 against recurrent breast cancer since 2003 and also applied HF10 to non-resectable pancreatic cancer since 2005. An oncolytic herpes simplex virus type 1, mutant HF10, has been isolated and evaluated for anti-tumor efficacy in syngeneic immunocompetent mouse models. From long time before clinical trial, we have found that the mutant virus can have remarkable potential to effectively treat cancer in experimental studies using animals, and that all of the surviving mice acquire resistance to rechallenge of the tumor cells. A number of studies have shown that HF10 is effective and safe for use in localized or peritoneally disseminated malignant tumors of non-neuronal origin in animals. Pilot studies using HF10 have been initiated in patients with metastatic breast cancer. For each patient, 0.5 ml HF10 diluents at various doses were injected into test nodule, and 0.5 ml sterile saline was injected into a second nodule. All patients were monitored for local and systemic adverse effects, and the nodules were excised 14 days after viral injection for histopathological studies. All patients tolerated the clinical trial well. While no adverse effects occurred, there was cancer cell death and 30-100% regression histopathologically in recurrent breast cancer. As mentioned above, intratumoral injection of mutant herpes simplex virus HF10 for recurrent metastatic breast cancer was safe and effective. Also a trial for non-resectable pancreatic cancer being carried out on the basis of the above result has proved to be innocuous and has been in progress to assess the clinical benefit and enhance the potentiality of HF10 against cancer.
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PMID:Clinical experiment of mutant herpes simplex virus HF10 therapy for cancer. 1734 8

Primary drug resistance, defined as disease progression as best response to treatment, presents an important problem in everyday clinical practice. Primary taxane resistance, reported in up to 55% of patients with breast cancer, plays a critical role in minimizing the efficacy of taxane-based chemotherapy for metastatic breast cancer (MBC). The epothilones are a novel class of antineoplastic agents, developed to overcome tumor-resistance mechanisms. Ixabepilone, the first drug in this class, stabilizes microtubule polymerization, and induces cell-cycle arrest and apoptosis. Ixabepilone demonstrates low susceptibility to different and multiple mechanisms of drug resistance that play a crucial role in primary taxane resistance, such as tumor overexpression of neuronal-specific beta-tubulin isotype III and drug-efflux transporters. In phase II trials, ixabepilone demonstrated proven activity in patients with MBC whose tumors had primary or secondary resistance to taxanes and other agents. Ixabepilone also demonstrated activity in patients with tumor types such as renal-cell cancer and pancreatic cancer that are usually intrinsically insensitive to chemotherapy, including taxanes. To determine the activity of ixabepilone in patients with primary taxane resistance, a retrospective analysis of patient subsets from 2 clinical trials was conducted. Ixabepilone demonstrated clinical activity as monotherapy, and in combination with capecitabine, in patients with MBC who had disease progression as best response to previous taxane therapy. Response rates in patients with primary taxane resistance were comparable to responses observed in total patient populations. The clinical results support the hypothesis that ixabepilone can overcome or circumvent primary mechanisms of resistance to taxanes and other chemotherapeutic agents.
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PMID:Activity of ixabepilone in patients with metastatic breast cancer with primary resistance to taxanes. 1907 2

The American Society for Clinical Oncology (ASCO) determined that there were twelve major advances in medical oncology last year. Endocrine-responsive breast cancer benefits from tamoxifen or an aromatase inhibitor taken for more than five years. Zoledronic acid, a bisphosphonate, reduces the risk of breast cancer recurrence in premenopausal women undergoing hormonal-suppression therapy. Bevacizumab was for use in combination with paclitaxel in patients with metastatic breast cancer Cetuximab added to chemotherapy of non-small cell lung cancer patients increased survival by up to 21%. Adjuvant gemcitabine doubled disease-free survival in pancreas cancer. Adjuvant pegylated interferon cuts the risk of recurrent melanoma by 18%. Bendamustine abolishes signs of activity of chronic lymphocytic leukemia in 30% of patients. The HPV vaccine--now approved for prevention of cervical cancer--might have a role in preventing oral cancers and a review of 45 studies showed that oral contraceptives reduce the risk of ovarian cancer.
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PMID:[Oncology]. 1927 50

Ribonucleotide reductase 1 (RRM1) is a determinant of gemcitabine efficacy in non-small-cell lung cancer and pancreatic cancer. We investigated the protein levels of RRM1 and two other DNA repair enzymes, ERCC1 and BRCA1, in 55 metastatic breast cancer (MBC) patients undergoing gemcitabine-based chemotherapy. With automated in situ protein quantification (AQUA v1.6), the average scores for RRM1, ERCC1, and BRCA1 ranged from 245.6-2774.1, 74.0-410.3, and 54.4-1833.1, respectively. They were significantly associated with each other (Spearman's rho > or = .36; p < or = .007). Given their pattern of distribution, RRM1 and BRCA1 are potentially suitable markers for clinical decision making in MBC.
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PMID:In situ protein expression of RRM1, ERCC1, and BRCA1 in metastatic breast cancer patients treated with gemcitabine-based chemotherapy. 1996 94

Capecitabine is an orally available fluoropyrimidine carbamate that selectively delivers fluorouracil (5-FU) to tissues expressing high levels of thymidine phosphorylase (TP) such as tumors. The drug has demonstrated efficacy in metastatic breast cancer, colorectal, and pancreatic cancer. Although these are considered safe drugs, a growing body of literature reports adverse cardiac effects. Clinical trials indicate that capecitabine has a cardiac toxicity similar to that of infused fluoropyrimidines such as 5-FU. Here, we review cardiotoxicity in the use of fluoropyrimidines, with particular attention toward capecitabine. We also describe a severe, reversible cardiac event that occurred in a 39-year-old woman, with no cardiac risk factors, treated with capecitabine for advanced breast cancer. This review and our experience confirm that fluoropyrimidine cardiotoxicity is an infrequent but documented side effect. Oncology patients under treatment should be closely observed and monitored for cardiac symptoms with particular attention in case of signs or symptoms of cardiovascular complications. The implementation of cardio-oncology interdisciplinary teams should, in the future, reduce the impact of cancer treatment-associated cardiotoxicity syndromes.
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PMID:Capecitabine in breast cancer: the issue of cardiotoxicity during fluoropyrimidine treatment. 2172 48

Paclitaxel and docetaxel are established as the standards of care, either as monotherapy or in combination with other cytotoxic agents in metastasic breast cancer. In order to improve the efficiency of solvent-based paclitaxel and to overcome its drawbacks in terms of safety, a solvent-free formulation has been developed. This work is a review of the albumin-bound paclitaxel data relative to its pharmacodynamic and pharmacokinetic profiles, its therapeutic efficiency and its safety of use. The activity of albumin-bound paclitaxel in phase II and III trials indicates its significant clinical efficiency in the treatment of metastatic breast cancer. In lung and pancreatic cancer and in melanoma, the use of albumin-bound paclitaxel leads to interesting results which require further investigations. Preclinical and clinical studies have shown that albumin-bound paclitaxel is associated with a better tolerance compared to standard paclitaxel.
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PMID:Albumin-bound paclitaxel: the benefit of this new formulation in the treatment of various cancers. 2157 19


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