Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This Phase II study was designed to determine the efficacy and tolerability of vorozole (R83842), a new nonsteroidal aromatase inhibitor, in postmenopausal women with advanced breast cancer in progression being treated with tamoxifen, and to correlate these effects with the hormonal profile and plasma drug levels. Twenty-nine eligible women with estrogen receptor-positive or unknown disease were treated with 2.5 mg vorozole once daily p.o. until disease progression. All 29 are evaluable for toxicity and 27 for response as assessed by International Union Against Cancer (UICC) criteria. After a median follow-up of 8 months, 3 patients (11%) had partial remission of their disease for 14, 15, and 16 months and 14 patients had disease stabilization for 7-24 months (median, 12). Patients with a normal carcinoembryonic antigen level (</=3 mm/liter), those without bone metastases, older women, and those with a long disease-free interval were most likely to benefit from treatment. Estradiol decreased from pretreatment levels of 9. 2-85 pm/liter (mean, 24) to below detection (9.2 pm/liter) and estrone from 64-311 pm/liter (mean, 144.3) to 19-116 pm/liter (mean, 57) after 1 month. Serum follicle-stimulating and luteinizing hormone levels rose from 9-74 IU/liter (mean, 35.3) and 3.3-38 IU/liter (mean, 17.8) to 10-102 IU/liter (mean, 44.6) and 1.6-70 IU/liter (mean, 24.2) and sex hormone-binding globulin fell from 27-138 nm/liter (mean, 65.4) to 15-109 nm/liter (mean, 53.8) after 1 month of treatment. Corresponding levels of androstenedione, dehydroepiandrosterone, free testosterone, and 17alpha-hydroxyprogesterone were unaffected. An adrenocorticotropic hormone stimulation test was normal in 18 patients 1 month after treatment commenced. Trough drug levels (measured by gas chromatography) ranged from 6.5-95 ng/ml (median, 24.5) at 1 month of treatment. Possible treatment-related side effects were mild and included malaise, anorexia and nausea, hot flashes, fluid retention, vaginal infection, alopecia, lightheadedness, and one allergic reaction which caused lip swelling. Vorozole, given orally, is a clinically active well-tolerated new treatment for breast cancer. Selective suppression of estrogen confirms its action as a specific aromatase inhibitor. Further trials to confirm its relative efficacy in postmenopausal disease and to explore its application in other settings are indicated.
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PMID:Phase II study of vorozole (R83842), a new aromatase inhibitor, in postmenopausal women with advanced breast cancer in progression on tamoxifen. 981 84

Eleven recurrent postmenopausal breast cancer patients with osseous or lung metastases were received fadrozole hydrochloride at a dose of 1 mg twice a day for more than 8 weeks. The median disease-free interval of these 11 patients with metastasis was 74 months. Out of 11 evaluable cases, 2 PR, 6 long-NC and 3 PD were observed. The overall response rate was 18.2% and the long-NC rate was 54.5%. The average overall duration of responses and long-NC were 567 days and 573 days, respectively. There was no adverse drug reaction. A combination therapy with fadrozole hydrochloride 2 mg daily and cyclophosphamide 100 mg orally on days 1-14 was given to 14 postmenopausal patients with recurrent breast cancer. The median disease-free interval of these 14 patients with metastasis was 33 months. There were 2 CR, 3 PR, 4 long-NC, 2 NC and 3 PD. The overall response rate and long-NC rate were 35.8% and 28.6%, respectively. The average overall duration of responses and long-NC were 700 days and 443 days, respectively. The adverse drug reactions were anorexia (Grade 2) and neutropenia (Grade 1 and 2). These results suggested that a combination therapy with fadrozole hydrochloride and cyclophosphamide can be effective and contribute to survival time in the treatment of postmenopausal breast cancer.
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PMID:[Clinical trial of fadrozole hydrochloride for postmenopausal patients with recurrent breast cancer]. 1039 24

Effects of DAC (doxifluridine (5'-DFUR), adriamycin (ADM), cyclophosphamide (CPA)) chemotherapy were evaluated in seven patients with advanced breast cancer. 5'-DFUR of 600 mg was orally daily, ADM of 40 mg/m2 was administered intravenously (bolus) at day 1 and CPA of 400 mg/m2 was administered intravenously (one shot) at day 1 and day 8. These were repeated as one cycle of 21 days. Two complete responses, three partial responses and two progressive diseases were obtained, and the response rate was 71% (95% confidence interval: 29-96%). The side-effects of more than grade 3 were observed in leucocytopenia (4/7), neutrocytopenia (6/7), anorexia (2/7), nausea or vomiting (2/7) and alopecia (6/7). These results suggest that DAC chemotherapy is a novel, attractive regimen for treatment of advanced breast cancer. The randomized clinical trial is required to elucidate the efficacy of 5-fluorouracil (5-FU) or its analogues and the significance of methods for their administration in management of patients with advanced breast cancer.
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PMID:[Effects of DAC (doxifluridine, adriamycin, cyclophosphamide) chemotherapy in advanced breast cancer patients]. 1041 Jan 46

Capecitabine is an orally administered fluoropyrimidine carbamate used for the treatment of paclitaxel- or anthracycline-refractory breast cancer. Capecitabine is metabolised via a 3-step process to the active agent fluorouracil. The final step of this process occurs preferentially in malignant tissue. In patients with paclitaxel-refractory breast cancer receiving capecitabine (2510 mg/m2/day for 2 weeks of a 3-week cycle) the objective tumour response rate was 20%. Disease progression occurred in 34% of patients and 40% had stable disease. In this trial, the median duration of response was 241 days. Disease progression or death occurred in 83% of patients, and median time to progression was 93 days. Median survival time was 384 days. In previously untreated patients with breast cancer, the response rate was higher and time to disease progression was longer after oral capecitabine (2510 mg/m2/day for 2 weeks of a 3-week cycle) than after intravenous cyclophosphamide, methotrexate and fluorouracil therapy. In clinical trials, generally gastrointestinal or haematological adverse events were reported most frequently. Other commonly reported events included hand-and-foot syndrome, fatigue, hyperbilirubinaemia, dermatitis and anorexia.
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PMID:Capecitabine. 1043 30

The effectiveness of combining mitomycin C (MMC), tamoxifen (TAM), and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) was evident in patients with estrogen receptor-positive (ER+) breast cancers. UFT, an oral preparation of tegafur and uracil at a molar ratio of 1:4, was reported to have higher antitumor effects than tegafur alone for patients with breast cancer. Therefore, the combined chemotherapy of MMC, TAM and UFT may possibly be effective for breast cancer. From 1988 to 1991. we studied the effects of postoperative adjuvant therapy for Japanese women with stage 11 breast cancer, all seen at 71 institutions in western areas of Japan. Five hundred and ninety four patients with stage II primary breast cancer who had undergone curative surgery, including total mastectomy and axillary lymph node dissection, were enrolled. On the day of surgery, each patient was given 13 mg/m2 of MMC intravenously. Patients with ER+ tumors were then assigned to group A or group B. Group A received 30 mg/day of TAM given orally from postoperative 2 weeks, for 2 years. Group B was additionally given an oral dose of 300 mg/day of UFT for 2 years, given concomitantly with 30 mg/day of TAM. Patients with ER- tumors were assigned to group C or group D. Group C were prescribed 300 mg/day of UFT, orally, from postoperative 2 weeks for 2 years, and group D were additionally given an oral dose of 30 mg/day of TAM together with 300 mg/day of UFT. There were no differences among the groups regarding prognostic factors or doses of MMC and TAM in ER+ patients and MMC and UFT in ER- patients. Toxicity rates for leukopenia, anorexia, and nausea/vomiting were higher in group B than in group A patients. There were no statistical differences in the overall survival and disease-free survival times between groups A and B, or groups C and D, for all eligible cases. In a retrospective subgroup analysis using Bonferroni's adjustments, the additional effect of UFT on the combined treatment of MMC and TAM lengthened the disease-free survival time for patients with premenopausal ER+ cancers (corrected P value by Bonferroni's adjustments <0.05). Multivariate analysis showed that effects of the combined treatment of MMC, TAM, and UFT was significantly related to the menopausal status (P<0.01). Our findings show that postoperative ingestion of MMC, TAM, and UFT was effective for patients with premenopausal ER+ stage II breast cancer.
Breast Cancer Res Treat 1999 Jul
PMID:Postoperative chemo-endocrine treatment with mitomycin C, tamoxifen, and UFT is effective for patients with premenopausal estrogen receptor-positive stage II breast cancer. Nishinihon Cooperative Study Group of Adjuvant Therapy for Breast Cancer. 1057 4

This prospective randomized study aimed at establishing the optimal postoperative adjuvant chemotherapy regimen for premenopausal n+ breast cancer patients. The treatments were Regimen A, comprising 6 courses of CMF (cyclophosphamide, 100 mg/body on days 1-14; methotrexate, 40 mg/m2 on days 1 and 8; and 5-fluorouracil, 500 mg/m2 on days 1 and 8), and Regimen B, consisting of UFT (300 mg/day) and tamoxifen (30 mg/day) administered orally each day for 2 years. Telephone registration allocated the patients to the treatment groups by the minimization method in relation to the T category, number of n+ lesions and estrogen receptor status. Forty-five patients were registered, and 44 of them were eligible (22 cases each to Regimen A and Regimen B). The principal background factors showed no biases between the groups. The adverse reaction incidence was significantly higher with Regimen A (90.9% vs 22.7%). The 5-year survival rate was 89.8% with Regimen A and 100% with Regimen B, while the 5-year disease-free rates were 64.5% and 76.3%, showing no statistical significance. Regimen B showed a better QOL rating after 6 months of therapy in relation to nausea-vomiting and hair loss, and after 24 months in relation to appetite, sleep, performance status, happiness, anorexia and hair loss.
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PMID:[Randomized comparative study of CMF (cyclophosphamide, methotrexate and 5-fluorouracil) and UFT-tamoxifen regimens as adjuvant chemotherapy after surgery for breast cancer: Tochigi Prefectural Study Group for Post-Breast Cancer Adjuvant Chemotherapy]. 1092 84

The aim of the study was to compare the quality of life (QL) of patients treated with single-agent paclitaxel versus doxorubicin as first-line chemotherapy for advanced breast cancer. 331 patients with advanced breast cancer were randomised, with 294 eligible for analysis. Patients completed both the EORTC QLQ-C30 questionnaire and the Rotterdam Symptom Checklist (RSCL) with six additional items, at baseline and after the third, fifth and seventh cycles of chemotherapy. A significant difference in progression-free survival in favour of doxorubicin caused a bias in the data with differences in expected completion rates of questionnaires beyond cycle three. Therefore, statistical comparisons were performed only for the first three cycles. Baseline compliance was 64% and 61% for the QLQ-C30 and RSCL questionnaires, respectively. Doxorubicin was associated with significantly more nausea/vomiting (P=0.001), loss of appetite (P=0.010) and a greater burden of disease and treatment (P=0.044), but with less bone pain (P=0.042) and rash (P=0.045) than paclitaxel. Both treatments were associated with improved emotional function and reduction in psychological distress at cycle 3. Longitudinal data suggested that doxorubicin was associated with less pain, specifically bone pain. Doxorubicin was more active but may have had more side-effects during the first three cycles. Long-term QL outcomes could not be assessed.
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PMID:Randomised trial of paclitaxel versus doxorubicin as first-line chemotherapy for advanced breast cancer: quality of life evaluation using the EORTC QLQ-C30 and the Rotterdam symptom checklist. 1093 Jul 96

The aim of the project was to identify clinical and quality of life (QL) factors that together predict survival and response to chemotherapy in advanced breast cancer. Potential prognostic factors were studied in 187 women with baseline QL data from a trial of paclitaxel versus doxorubicin as first-line chemotherapy. Demographic and clinical factors studied were age, performance status, dominant site of disease and preceding disease-free interval (DFI). Factors from the EORTC QLQ-C30 were all function scales, fatigue, nausea/vomiting, pain, dyspnoea, insomnia, loss of appetite and global QL. The proportional hazards regression model with stratification for treatment, and the logistic regression model adjusting for treatment arm were used for univariate and multivariate analyses of survival and response to treatment, respectively. For survival, multiple sites of visceral disease, pain, global QL and fatigue were significant prognostic factors in the univariate analysis. The final multivariate model predicted poor survival with multiple sites of visceral disease (P=0.003), DFI </=2 years (P=0.026) and pain (P=0.003). For response, age, dyspnoea, fatigue and global QL were significant predictive factors in the univariate analysis. The final multivariate model for response selected DFI (P=0.009), multiple sites of visceral disease (P=0.037) and dyspnoea (P=<0.001) using forward selection, but model instability was indicated by the inclusion of fatigue and emotional function in the final model when backward selection was used. In addition to known clinical factors, patient-assessed QL variables appear to be prognostic for survival and response to chemotherapy in women with advanced breast cancer. However, identification of prognostic factors from responses to questionnaires may be unstable, and their reliability and clinical utility should be tested prospectively.
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PMID:Identification and interpretation of clinical and quality of life prognostic factors for survival and response to treatment in first-line chemotherapy in advanced breast cancer. 1093 Jul 97

A multi-center, randomized controlled collaborative study was conducted in 310 institutions located thruoughout Japan for 3 years and 9 months from February 1985 until October 1988 to evaluate the efficacy of post-operative adjuvant therapy for patients who had previously undergone curative surgery for treatment of Stage III a breast cancer. Patients with estrogen receptor-positive [ ER(+)] breast cancer were treated with two types of regimens, ie, cyclophosphamide+adriamycin+fluorouracil (CAF; 2 cycles) +Futraful(FT) or CAF (2 cycles+FT+tamoxifen (TAM), and the clinical benefit of additional use of TAM was evaluated. Of the 509 ER(+) patients registered for the trial, 473 patients (92.9%) were eligible for evaluation.The 5-year survival rate was 77.2% for the CAF+FT group and 74.6% for the CAF+FT+TAM group, and the 5-year disease-free survival rate was 56.7% for the CAF+FT group and 59.2% for the CAF+FT+TAM group. Neither the survival rate nor the disease-free survival rate differed significantly between the groups. Analyses by factor revealed that the 5-year disease-free rate for lymph node-negative patients in the CAF+FT+TAM group was significantly higher than that for the corresponding patients in the CAF+FT group. No differences were noted in the incidence of adverse reactions between the two treatment groups, other than an increase in LDH (the frequency of which was higher in the CAF+FT+TAM group than in the CAF+FT group). Patients with estrogen receptor-negative [ ER(-)]breast cancer were treated with two types of regimens, ie, CAF+FT or CAF+FT+adriamycin(ADR), and the clinical benefit of the combined use of intermittent doses of ADR was evaluated. Of the 514 ER(-) patients registered in the trial, 478(93.0%) were eligible for evaluation. The 5-year survival rate was 64.9% for the CAF+FT group and 63.0% for the CAF+FT+ADR group, and the 5-year disease-free survival rate was 59.2% for both CAF+FT and CAF+FT+ADR groups. Neither the survival rate nor the disease-free survival rate differed significantly between the groups. There were no significant differences between these groups in analyses by nodal or menopausal status. The incidences of adverse reactions including anorexia, nausea/vomiting and alopecia were higher in the CAF+FT+ADR group than in the CAF+FT group.
Breast Cancer 1997 Jul 31
PMID:Efficacy of Post-operative Adjuvant Therapy for Stage IIIa Berast Cancer: Futraful vs Futraful+Tamoxifen for ER-positive Patients and Futraful vs Futraful+Adriamycin for ER-negative Breast Cancer. 1109 84

BACKGROUND: Chemotherapeutic regimens, such as cyclophosphamide + doxorubicin + 5FU (CAF) or cyclophosphamide + methotrexate + 5FU (CMF), are sometimes used in combination with endocrine or radiotherapy as a standard first line of treatment for recurrent or metastatic breast cancer. However, many cases are, or become, refractory to these treatments. METHODS: Twenty-one women with recurrent or metastatic breast cancer who previously underwent treatment were administered our original regimen of combinationchemotherapy, MFL-P: Day 1, bolus methotrexate (MTX) 50 mg/body (median dose, 33 mg/m(2); range, 29-35 mg/m(2)) and 4 hours later 5-fluorouracil (5FU) 750 mg/body/h (median dose, 497 mg/m(2)/h; range, 441-528 mg/m(2) /h); Days 2-3, bolus leucovorin(LV) 15 mg/body every 8 h x 3; Days 2-5, 72 hours continuous 5FU 750 mg/body/24h; Day 6, cisplatin (CDDP) 50 mg/body/h (median dose, 33 mg/m(2)/h; range, 29-35 mg/m(2) /h) with sufficient hydration. The subjects ranged in age from 26 to 63 years (mean age, 51.3 years). RESULTS: One complete and 9 partial responses were achieved among the 20 patients (response rate, 50%). In 1 patient, diffuse liver metastasis was not measurable. Among various metastatic sites, a higher response rate was observed especially for soft tissue lesions (skin, chest wall and lymph nodes; 9 responders among 11 lesions). On the other hand, in visceral or skeletal metastases, the response rate was poor. The adverse effects were tolerable in all patients, except for common low-grade stomatitis or anorexia. CONCLUSION: MFL-P is useful as a second or third line of therapy for patients with refractory, recurrent or metastatic breast cancer with soft tissues lesions.
Breast Cancer 1999 Jul 25
PMID:MFL-P Chemotherapy for Pretreated Metastatic Breast Cancer Patients: A Regimen with Triple Biochemical Modulation by MTX-5FU, LV-5FU and 5FU-CDDP. 1109 14


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