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)

Ftorafur is a 5-fluorouracil analogue which is slowly metabolized to 5-FU, resulting in prolonged therapeutic levels of this latter drug. Ninety-one evaluable patients with metastatic breast cancer were treated with Ftorafur, Adriamycin, cyclophosphamide, and BCG (ACFTOR-BCG), in an attempt to increase the effectiveness of the program or decrease its myelosuppressive toxicity. The results of this trial were compared to those previously reported with the combination of 5-FU, Adriamycin, cyclophosphamide, and BCG (FAC-BCG). Overall objective response rates were 65% and 76% for ACFTOR-BCG and FAC-BCG, respectively. Durations of response were 12 months and 14 months for ACFTOR-BCG and FAC-BCG (p = 0.53). The median survival of responders was 22 and 23.9 months, respectively. Substantial toxicity was observed with Ftorafur: nausea and vomiting severe enough to cause weight loss was observed in a substantially higher fraction of the patients treated with this drug than with 5-FU. Other side-effects, which were not observed with the 5-FU combination, were somnolence, dizziness, personality changes, tremor, ataxia, and confusion. No differences in myelosuppressive toxicity were observed between the two combinations, and the incidence of infectious complications was identical. The combination of Ftorafur, Adriamycin, cyclophosphamide and BCG did not offer any advantages with respect to increased effectiveness or reduced toxicity over the FAC-BCG regimen in breast carcinoma.
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PMID:Ftorafur, adriamycin, cyclophosphamide and BCG in the treatment of metastatic breast cancer. 38 55

One hundred and fourteen evaluable patients with metastatic breast cancer were treated with a program consisting of 5-FU, Adriamycin, cyclophosphamide (FAC) and nonspecific immunotherapy with Levamisole. The results of this treatment program were compared to those observed with FAC and Bacillus Calmette Guerin (BCG) and FAC chemotherapy alone, both groups treated prior to the study reported in this paper. The overall response rates and complete response rates for all three treatment regimens were identical. The duration of remission, survival of all patients and survival of responders was similar for both chemoimmunotherapy regimens, being superior to the FAC chemotherapy alone group. Immunotherapy with Levamisole was well tolerated and side-effects were experienced by less than one-fourth of the patients. Overall, Levamisole was better tolerated than BCG and was easier to administer than the latter drug. These results suggest than nonspecific immunotherapy with Levamisole might prolong remission and survival of patients with metastatic breast cancer. Since the results achieved with BCG and Levamisole appear similar, the therapeutic ratio favors the use of Levamisole.
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PMID:Combined chemoimmunotherapy for advanced breast cancer: a comparison of BCG and levamisole. 42 16

Seventy-two women with metastatic breast cancer were treated with multiple-agent chemotherapy. Fifty women were treated with 5 drugs in combination: 5-FU, methotrexate, vincristine, cytoxan, and prednisone; 22 were treated with the combination of 3 drugs: 5-fu, cytoxan, and prednisone. In 14 patients receiving 5 drugs and in 22 receiving 3 drugs, the multiple chemotherapy was the primary palliative treatment of extensive visceral metastases unsuitable for adrenalectomy. Results were similar with 6 responders in 14 (0.43) receiving 5 drugs, and 10 responders in 22 (0.45) receiving 3 drugs. The remaining 36 patients who were given 5-drug therapy all had previous adrenalectomy, and there were 16 responders (0.44). Toxicities from 3-drug treatment were substantially less severe than those from the 5-drug combination therapy. Whereas treatment-related death occurred in 6 of 50 patients receiving the 5-drug combination, no such incidence occurred in those receiving 3-drug combination therapy.
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PMID:Combination chemotherapy in the treatment of advanced breast cancer. 99 8

In this study, 30 patients with metastatic breast cancer were treated with 5-Fluorouracil (5-FU) and high-dose Folinic acid, using a new sequential dosing schedule. Our treatment consisted of one day i.v. infusion of 500 mg/m2 of Folinic acid over two hours. One hour after the beginning of Folinic acid infusion, 5-FU (500 mg/m2) was given by i.v. bolus injection. The complete and partial response rates achieved (CR+PR) were 21% in a population of patients pretreated with chemotherapy including 5-FU. Cutaneous and bone metastasis responded best to our treatment. There were no treatment related deaths or withdrawals from the study. The drug related toxicities observed in this study were usually mild to moderate and easily controllable. Thus preliminary results of our study suggest that response rate, quality of life and time to disease progression for the responders improved by this sequential treatment.
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PMID:Phase II trial with 5-fluorouracil and high-dose folinic acid, using new sequential dosing schedule, in pretreated advanced breast cancer patients. 147 34

Between September 1988 and August 1990, we treated 35 women with metastatic breast cancer with a novel regimen containing mitoxantrone, fluorouracil (5-FU), and high-dose leucovorin. This regimen was designed to take full advantage of the favorable toxicity profiles of these agents while maintaining a high level of activity. All patients had received previous chemotherapy (adjuvant only, 15 patients; at least one metastatic regimen, 20 patients). Seven patients had received previous doxorubicin, but none within 6 months of study entry. Of 31 assessable patients, 20 (65%) had objective responses (two complete, 18 partial), with a median response duration of 6 months (range, 3 to 16+ months). Four patients with bone metastases (abnormal bone scan only) and pain were not considered assessable by strict response criteria; two of these patients had sustained symptomatic relief for 6 and 8 months, respectively. Myelosuppression was the most frequent toxicity but was mild in most patients; only four hospitalizations for fever and neutropenia were required (2% of courses). No severe thrombocytopenia occurred and no RBC transfusions were required. Alopecia, mucositis, and nausea/vomiting were uncommon and were not severe in any patient. The combination of mitoxantrone, 5-FU, and high-dose leucovorin is well tolerated and active as a first- or second-line treatment for metastatic breast cancer. Comparison with other standard regimens for breast cancer is indicated.
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PMID:Mitoxantrone, fluorouracil, and high-dose leucovorin: an effective, well-tolerated regimen for metastatic breast cancer. 191 22

A new combination of mitoxantrone, folinic acid (leucovorin), and infusional fluorouracil (5-FU) was administered to 57 previously treated patients with metastatic breast cancer to evaluate the response rate, response duration, and toxicity of this regimen. Fifty-three patients who received 313 courses of therapy were assessable for response and toxicity. Median age was 48 years (range, 33 to 80 years), and the patients had received an average of 1.5 chemotherapy regimens before this study. Of 53 assessable patients, 24 (45%, or 42% of all entered patients) experienced partial responses (PRs) with a median duration of 6 months (range, 2 to 13 months). Nine (69%) of 13 assessable patients without prior doxorubicin treatment responded, compared with 15 (38%) of 40 with prior doxorubicin (P less than .05). Toxicity was generally mild with dose reductions necessitated more often by mucositis and/or diarrhea than by myelosuppression. One patient with prior high-dose doxorubicin treatment developed congestive heart failure. The combination of mitoxantrone, leucovorin, and infusional 5-FU is an active and well-tolerated regimen for metastatic breast cancer and deserves further evaluation in patients without prior doxorubicin therapy.
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PMID:Phase II study of mitoxantrone, leucovorin, and infusional fluorouracil for treatment of metastatic breast cancer. 191 22

Leucovorin enhances the cytotoxicity of fluorouracil (5-FU) in patients with colorectal cancer and may increase the efficacy of combination chemotherapy regimens containing 5-FU. To determine the maximum tolerated dose of 5-FU with leucovorin for use in combination with cyclophosphamide and doxorubicin, we conducted a phase I/II trial in 20 patients. The doses of leucovorin (200 mg/m2 on days 1-5), cyclophosphamide (500 mg/m2 on day 1), and doxorubicin (40 mg/m2 on day 1) were held constant, while the dose of 5-FU was escalated in cohorts of patients beginning at 150 mg/m2 on days 1-5. Cycles were repeated every 3 weeks. Significant mucositis, diarrhea, and myelosuppression were infrequently observed in patients receiving up to 250 mg/m2 5-FU on days 1-5. In contrast, at a dose of 300 mg/m2 on days 1-5, three of six patients had granulocyte count nadirs of less than 500/microL during the first cycle of therapy, and two of these three had platelet counts of less than 25,000/microL. In addition, two patients treated at this dose had significant mucosal toxic effects, and three had insufficient recovery to permit a second course by day 22. Among 14 patients with assessable breast cancer, there were one complete and nine partial responses (response rate 71%). Leucovorin modulation of 5-FU can be safely incorporated into combination chemotherapy with cyclophosphamide and doxorubicin and provides a highly active regimen for treatment of metastatic breast cancer. Further study will be required to determine whether the addition of leucovorin significantly enhances the activity of this regimen.
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PMID:Phase I/II study of cyclophosphamide, doxorubicin, fluorouracil, and leucovorin for treatment of metastatic adenocarcinoma. 207 8

Previous clinical studies have suggested that 4'-O-tetrahydropyranyl-doxorubicin (THP) as well as 5-fluorouracil/high-dose folinic acid (5-FU/HDFA) are active and well-tolerated drugs in breast cancer treatment. This phase I-II study was designed to determine the maximum tolerated dose (MTD) of THP in combination with 5-FU/HDFA as a weekly schedule and to examine the activity and safety of this drug regimen in patients with advanced breast cancer. 5-FU and HDFA were set at doses of 350 mg/qm i.v. and 500 mg/qm i.v., respectively, whereas the THP dose has been escalated in increments of 5 mg/qm i.v. beginning at a dose level of 10 mg/qm until reaching of MTD in at least four patients in one dose level. For determination of MTD the first six cycles of each patient have been taken into account. Up to July 1990, 21 patients previously not treated with chemotherapy for metastatic breast cancer were entered into the study; the latest patient entered at 35 mg/qm THP dose level. A total of 270 cycles have been administered so far. Anemia and leukopenia was limited to ECOG grades I and II. Other toxicities were mild or moderate. No acute or subacute cardiotoxicity has been observed. Up to July 1990, MTD had not been reached. In the second part of the study, at least another 14 patients have to be entered in a dose level one below the MTD to evaluate the activity and safety of this regimen in a phase II trial.
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PMID:Combination therapy of 4'-O-tetrahydropyranyl-doxorubicin, 5-fluorouracil, and high-dose folinic acid in patients with advanced breast cancer: a phase I-II study (preliminary results). 229 57

The efficacy and toxicity of leucovorin 500 mg/m2 administered intravenously (IV) over 30 minutes daily for five days followed in one hour by fluorouracil (5-FU) 375 mg/m2 administered IV daily for five days, each given every 3 weeks, was assessed in 54 previously treated patients with metastatic breast cancer. An overall objective response rate of 24% was achieved (95% confidence interval, 13% to 38%), with an additional 56% of patients maintaining stable disease. Eleven of 12 patients who responded had received previous 5-FU therapy. Toxicity of this regimen included grade 3 diarrhea in 13%, grade 3 or 4 mucositis in 33%, grade 3 or 4 granulocytopenia in 65%, and grade 3 or 4 thrombocytopenia in 19%. Delay of treatment was required for hematologic toxicity in 44 patients. Thirty-eight patients required dose reductions due to toxicity. Biochemical evaluation of tumor biopsy specimens obtained from 17 patients used as their own controls with and without leucovorin was performed. These studies reveal an increased stabilization of the 5-fluorodeoxyuridylate (FdUMP)-thymidylate synthase (TS) folate ternary complex with the addition of leucovorin. There was a 71% +/- 14% occupancy or inhibition of the enzyme with the use of both 5-FU and leucovorin, v 30% +/- 13% for 5-FU alone (P2 less than .037). The percent TS bound in responding patients was substantially higher than in those patients with progressive disease. Finally, the mean total tumor TS pre-therapy in seven patients was 31 fmol/mg compared with a mean of 81 fmol/mg in these same seven patients 24 hours after therapy. This 2.6-fold increase suggests that there is an induction of the enzyme, TS, with 5-FU treatment.
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PMID:Fluorouracil and high-dose leucovorin in previously treated patients with metastatic breast cancer. 266 35

The predictive value of estrogen receptor (ER) level for response to chemotherapy was studied in 182 patients with metastatic breast cancer in a prospective study. Patients were stratified according to ER status and dominant site of disease and randomized to one of three regimens: cyclophosphamide, 5-Fluorouracil, and prednisone (CFP) versus CFP, methotrexate, and vincristine (CFPMV) versus doxorubicin and cyclophosphamide (AC). There was no significant differences in all response categories (P = 0.21), was taken as a predictor for response to chemotherapy, there was no significant difference in overall response (P = 0.61) between ER+ (62/108, 57%) and ER- patients (31/49, 63%). However, there was a significant trend toward a higher degree of response in ER- patients (more complete response [CR] nine of 49, 18%, and fewer failures six of 49, 12%) than in ER+ (less CR seven of 108, 7%, and more failures 37/108, 34%) (P = 0.006). Patients with higher measured levels of ER showed worse response (Kendall's tau C, P = 0.026). This trend for ER- patients to have better response than ER+ patients was generally consistent, regardless of the predominant site of metastases or chemotherapy regimen (P = 0.04 for CFP; P = 0.08 for CFPMV; and P = 0.20 for AC). The advantage of a better response for ER- patients was nullified by an earlier relapse which was reflected in longer duration of remission, time to treatment failure, and survival in favor of ER+ patients (12.3 months versus 7.3 months remission duration, 18.7 months versus 13.6 months survival in partial responders). These data suggest that ER- patients respond to a higher extent to chemotherapy but relapse sooner than ER+ patients, suggesting a more rapid growth for ER- tumors. In patients with ER- tumors and poorer prognosis on conventional chemotherapy, new trials of intensive consolidation after response should be considered.
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PMID:Differential response to chemotherapy in metastatic breast cancer in relation to estrogen receptor level. Results of a prospective randomized study. 273 Nov 20


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