Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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).
 ...
PMID:Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer. 168 8

Sixty patients with metastatic breast cancer refractory to prior doxorubicin combinations were randomized by performance status, dominant disease site, and number of involved organ sites to receive vindesine either as a bolus injection of 3-4 mg/m2 iv every 10-14 days or as a continuous 5-day infusion of 1-1.2 mg/m2/day every 21 days. There were two patients with partial responses (7%) and six with stable disease among the 26 evaluable patients who received bolus injections. Of the 25 evaluable patients who received continuous infusions, seven achieved a partial response (28%) and 11 had stable disease (0.001 less than P less than 0.005). Thirteen patients, after failing to respond to bolus vindesine, were given continuous infusions. Of these, 11 were evaluable and four had partial response (36%). Responses were seen in all organ sites of involvement, with response duration ranging from 2 to 9+ months. Side effects included nausea, vomiting, stomatitis, constipation, neuropathy, fever, and myelosuppression. Except for myelosuppression, which was more evident with the continuous infusion schedule, no significant difference was seen in the frequency of side effects encountered with the two schedules. These results confirmed that there is an improved therapeutic index for vindesine when it is given as a continuous 5-day infusion.
 ...
PMID:Vindesine in the treatment of refractory breast cancer: improvement in therapeutic index with continuous 5-day infusion. 727 12

Taxol was evaluated in metastatic breast cancer in three trials. In the first, a phase II study, 25 patients who had received only one prior regimen of chemotherapy received Taxol (starting dose of 250 mg/m2). The response rates were 12% complete, 44% partial, and 32% minor. The median duration of response was 9 months (range, 3 to 19 months). The median survival was 20 months (range, 5 to 29+ months). Toxic effects were granulocytopenia less than 500/mm3 in 85% of all courses but serious infection in only 6% of courses, myalgias, and cumulative neuropathy. The second trial was a phase I study of Taxol by 24-hour infusion sequenced with doxorubicin by 48-hour infusion as initial chemotherapy for metastatic disease. In arm 1, Taxol preceded doxorubicin. The starting doses were 125 mg/m2 Taxol, 60 mg/m2 doxorubicin. Neupogen (5 micrograms/kg) was given subcutaneously on days 5 through 19. Ten patients received 96 courses. The maximum tolerated dose was defined by mucositis and infection at the starting dose. Cumulative thrombocytopenia occurred in subsequent courses. The unexpectedly severe toxic effects at doses that were low by comparison to other studies suggested schedule-related toxicity. Therefore, in arm 2 the sequence has been reversed: doxorubicin precedes Taxol. Doses have been escalated to 180 mg/m2 Taxol with 60 mg/m2 doxorubicin without dose-limiting toxic effects occurring. The third trial, a phase II study in patients who have received three or more prior chemotherapy regimens, is ongoing. Twenty-one of a planned 35 patients have been entered. Taxol has shown significant antitumor activity in minimally pretreated patients.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The M. D. Anderson Cancer Center experience with Taxol in metastatic breast cancer. 791 22

MMM (mitomycin 7-8 mg/m2 i.v.) every 6 weeks; mitoxantrone 7-8 mg/m2 i.v. every 3 weeks; methotrexate 35 mg/m2 i.v. every 3 weeks) is a new combination chemotherapy regimen for advanced breast cancer. It has been compared in two complementary randomized trials with CMF (cyclophosphamide 100 mg orally, days 1-14; methotrexate 35 mg/m2 i.v. days 1 and 8; 5-fluorouracil 1 g i.v. days 1 and 8; courses repeated at 28-day intervals) and VAC (vincristine 1.4 mg/m2 every 3 weeks, anthracycline 30 mg/m2 every 3 weeks, cyclophosphamide 400 mg/m2 every 3 weeks) in patients with advanced metastatic breast cancer. In the first trial, which involved 227 patients, 53% of patients receiving MMM and 49% receiving VAC responded to treatment. There was no significant difference between treatment groups in median response duration or survival. Incidence of neuropathy, alopecia, and nausea and vomiting was significantly higher in patients receiving VAC. Hematologic toxicity was greater in the MMM group. In the second trial, which involved 120 patients, 51% of patients receiving MMM and 60% receiving CMF responded to treatment. Again, there was no significant difference between treatment groups in median response duration or survival. Both regimens were well tolerated with a low incidence of alopecia and serious nausea and vomiting, and there were no significant differences in toxicity. Significant reductions in serial left ventricular ejection fractions occurred in 4 patients given CMF and in 2 given MMM. MMM is an effective, well-tolerated regimen for advanced breast cancer, with toxicity similar to that of CMF and less than that of an anthracycline-containing regimen.
 ...
PMID:MMM (mitomycin/mitoxantrone/methotrexate): an effective new regimen in the treatment of metastatic breast cancer. 848 62

The first phase II study of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in breast cancer was completed at M.D. Anderson Cancer Center, and included 25 patients with metastatic breast cancer who had been previously treated with one chemotherapy regimen. Fourteen of these patients achieved a major objective response; the median response duration was 9 months, and the median survival time, 20 months. Additional trials showed that paclitaxel maintained its antitumor efficacy in patients with two and three prior chemotherapy regimens, including patients with anthracycline-resistant breast cancer. Combination therapy with doxorubicin showed that this combination was effective, although with the long infusion duration used for both agents, sequence-dependent toxic interactions were encountered. In combination with vinorelbine, dose-limiting toxicity included neutropenic fever and neuropathy. High-dose single-agent paclitaxel is currently being explored in the management of inflammatory breast cancer and as part of neoadjuvant chemotherapy for stages II and III operable disease.
 ...
PMID:The University of Texas M.D. Anderson Cancer Center experience with paclitaxel in breast cancer. 907 38

Epirubicin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is an active combination for the treatment of metastatic breast cancer. A multicenter pilot phase II trial evaluated this combination in 35 patients treated with epirubicin 75 mg/m2 given as a 1-hour infusion, immediately followed by paclitaxel 200 mg/m2 given as a 3-hour infusion every 3 weeks. All patients had metastatic disease and had received a maximum of one chemotherapy regimen for advanced disease. A 43% response rate was observed in 30 evaluable patients, with two complete responses (7%) and 11 partial responses (37%). All patients were evaluable for toxicity. Hematologic toxicity was common and dose limiting. All patients underwent blood counts three times weekly. Grade 4 neutropenia was extremely common (91%), occurring at approximately days 10 to 12 and resolving rapidly in most cases. Thrombocytopenia was rare. Dose reductions were necessary in 10 patients, primarily for myelosuppression, but due to neuropathy in two patients. Alopecia was universal. Cardiac function was measured in all patients every two cycles. Among the first 24 evaluable patients, left ventricular ejection fraction decreased to below 40% in three patients, all of whom had received prior anthracyclines. Treatment was discontinued in one patient, who experienced no further deterioration. Under the auspices of the United Kingdom Coordinating Committee for Cancer Research, a randomized phase III study has been initiated in the United Kingdom to compare this combination of epirubicin/paclitaxel with combination epirubicin/cyclophosphamide. The primary end point of this study is progression-free survival, and the intention is to recruit 350 to 700 patients over the next 2 years.
 ...
PMID:A phase II trial of epirubicin plus paclitaxel in metastatic breast cancer. United Kingdom Coordinating Committee for Cancer Research Breast Cancer Sub-Committee. 937 92

In an ongoing effort to establish the most appropriate dose and administration schedule for paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), the feasibility and safety of weekly 1-hour infusions were evaluated in 16 women with metastatic breast cancer previously treated with at least one chemotherapy regimen. Paclitaxel was administered on an outpatient basis at a starting dose of 100 mg/m2/wk for 4 consecutive weeks, with 4-week cycles continued until disease progression or the onset of intolerable toxicity. With 215 weekly infusions administered so far (median, 13 per patient), no episodes of febrile neutropenia have occurred, and no hematopoietic growth factors have been used. Plans for dose escalation were abandoned after grade 3 sensorimotor neuropathy developed in five of nine patients treated at paclitaxel 110 to 120 mg/m2. With dose escalation eliminated, further severe neurotoxicities were rare, but some degree of cumulative peripheral neuropathy was noted in all but three patients. No acute hypersensitivity reactions were noted. To date, six of 15 evaluable patients have achieved a major response to therapy, with one complete response and five partial responses. Four other patients had a minor response to therapy, one patient had an early death due to autopsy-proven extensive pulmonary microvascular carcinomatosis, and five patients have stable disease. Although the potential neurotoxicity of this regimen merits attention, the overall profile of a high therapeutic index, manageable toxicity, and convenient administration schedule makes this an attractive treatment alternative for patients with metastatic breast cancer.
 ...
PMID:Dose-dense therapy with paclitaxel via weekly 1-hour infusion: preliminary experience in the treatment of metastatic breast cancer. 937 99

The optimal dose and schedule for paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients with advanced breast cancer are not known. Based on our phase I study in non-small cell lung cancer, in which the dose intensity of paclitaxel was successfully escalated by using a weekly schedule, we initiated a phase II study of weekly paclitaxel in previously untreated patients with metastatic breast cancer (MBC) and locally advanced breast cancer (LABC). Treatment consists of weekly paclitaxel 175 mg/m2 intravenously over 3 hours for 6 weeks, followed by a 2-week break. Doses are modified for neutropenia (absolute neutrophil count < 1,500/microL), bilirubin levels greater than 1.5 times normal, or greater than grade 1 neuropathy. Patients with MBC continue treatment until disease progression. Patients with LABC receive one to two cycles before proceeding to surgery if resectable. Thus far, 15 patients, eight with MBC and seven with LABC, are assessable for response and/or toxicity. Most patients have required dose modification, with median delivery of 75% (cycle 1) and 50% (cycle 2) of the planned dose of paclitaxel. Neutropenia has been the most common cause of dose reductions, although only one patient required treatment for neutropenic fever. Six patients have developed grade 2/3 peripheral sensory neuropathy, but with dose reductions many have continued treatment with stable or improving neurologic symptoms. Objective responses have been seen in 12 of 14 assessable patients, including six with MBC (one complete response, five partial responses) and six with LABC (two complete responses, four partial responses), for an overall response rate of 86% (95% confidence interval, 66% to 96%). All responding LABC patients have been rendered free from disease at surgery. These preliminary results are very encouraging. Accrual to the study continues.
 ...
PMID:Weekly high-dose paclitaxel in metastatic and locally advanced breast cancer: a preliminary report. 937 2

The pharmacology, pharmacokinetics, clinical trials, adverse effects, and dosage and administration of docetaxel are reviewed. Docetaxel, a taxoid for the treatment of metastatic breast cancer, blocks the ability of tumor cells to divide in the M phase of the cell cycle. The drug has demonstrated superior cytotoxic activity in the treatment of a variety of cancers and enhanced activity in combination with other drugs. The pharmacokinetics of docetaxel appear to be linear. There seems to be a large interpatient variation in docetaxel biotransformation rates. Docetaxel has FDA-approved labeling for use in the treatment of patients with locally advanced or metastatic breast cancer whose disease has progressed during anthracycline-based therapy or who have relapsed during anthracycline-based adjuvant therapy. Phase II trials established the drug's role in first-line and second-line treatment of advanced breast cancer and as therapy for anthracycline-resistant advanced breast cancer, and they suggested a role for the agent in combination chemotherapy. The dose-limiting toxicity in all studies has been neutropenia. Other commonly noted adverse effects include mucositis, hypersensitivity reactions, and neuropathy. The recommended dosage for patients with metastatic or locally advanced breast cancer and normal hepatic function is 60-100 mg/m2 i.v. infused over one hour every three weeks. Docetaxel is not recommended for patients with liver metastases or impaired liver function because clearance of the drug is impaired. Docetaxel is effective in the treatment of metastatic and anthracycline-resistant breast cancer and may have a role in combination with other agents and in neoadjuvant and adjuvant therapy.
 ...
PMID:Docetaxel: a taxoid for the treatment of metastatic breast cancer. 977 40

Doxorubicin and paclitaxel both display strong antitumor activity in the treatment of breast cancer. The optimal schedule of this combination, however, remains undefined. In this phase I and pharmacologic study, we administered weekly 12 mg/m2 doxorubicin as a bolus infusion immediately followed by a 1 h 80 mg/m2 paclitaxel infusion to patients with metastatic breast cancer. A total of 119 weekly courses were delivered to seven patients. Grade IV neutropenia was observed in two patients at the first dose level, thus already defining the maximum tolerated dose. Pronounced non-hematologic toxicities were mild neuropathy (grade I: 39%) and stomatitis (grade I: 19%, grade II: 8%). No signs of cardiac toxicity were observed with this dose schedule. Three partial responses were achieved in this group of heavily pretreated patients. The pharmacokinetics of paclitaxel, doxorubicin and Cremophor EL with this schedule were analyzed. Overall, the schedule was well tolerated and combined with its preliminary response rate justifies further evaluation in phase II studies.
 ...
PMID:Phase I and pharmacologic study of weekly doxorubicin and 1 h infusional paclitaxel in patients with advanced breast cancer. 982 24


1 2 3 4 5 6 Next >>