PubMed Health⌕ Search

Biomedical subjects

A Buzdar

Publications and source records attributed to A Buzdar.

At least 19 recordsLinked to original sources
PubMed2006

Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial.

BACKGROUND: The Arimidex (anastrozole), Tamoxifen, Alone or in Combination (ATAC) trial was designed to compare the efficacy and safety of anastrozole with tamoxifen as adjuvant treatment for postmenopausal women with early-stage breast cancer. After an extended follow-up beyond the 5 years of treatment, we aimed to assess the safety, tolerability, and risk-benefit indices of these compounds. METHODS: We analysed postmenopausal women (mean age 64 years [SD 9]) with localised breast cancer randomly assigned to anastrozole (n=3125) or tamoxifen (n=3116). Efficacy measures, including death and risk-benefit indices, were analysed by intention to treat. Safety analyses were based on treatment first received (n=3092 for anastrozole and n=3094 tamoxifen). We calculated a risk-benefit analysis using the two global indices for the Women's Health Initiative and for Disease-Free Survival and Serious Adverse Events. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN18233230. FINDINGS: At median follow-up of 68 months (range 1-93), treatment-related adverse events occurred significantly less often with anastrozole than with tamoxifen (1884 [61%] vs 2117 [68%]; p<0.0001), as did treatment-related serious adverse events (146 [5%] vs 277 [9%]; p<0.0001) and adverse events leading to withdrawal (344 [11%] vs 442 [14%]; p=0.0002). Patients given anastrozole had significantly fewer overall events for the Global Index of the Women's Health Initiative (744 [24%] vs 851 [27%]; hazard ratio 0.85 [95% CI 0.77-0.94], p=0.001) and the Global Index of Disease-Free Survival and Serious Adverse Events (1453 [46%] vs 1594 [51%]; 0.88 [0.82-0.94]; p=0.0004). INTERPRETATION: Anastrozole is tolerated better than tamoxifen by postmenopausal women with early-stage breast cancer, and results in fewer serious adverse events. Furthermore, it has a more favourable overall risk-benefit profile and lower recurrence rate than tamoxifen.

Anastrozole↗
PubMed2003

Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses.

BACKGROUND: The first analysis of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial (median follow-up, 33 months) demonstrated that in adjuvant endocrine therapy for postmenopausal patients with early-stage breast cancer, anastrozole was superior to tamoxifen in terms of disease-free survival (DFS), time to recurrence (TTR), and incidence of contralateral breast cancer (CLBC). In the current article, the results of the first efficacy update, based on a median follow-up period of 47 months, are reported along with the results of an updated safety analysis, performed 7 months after the first analysis (median duration of treatment, 36.9 months). METHODS: DFS, TTR, CLBC incidence, and safety were assessed in the same patient group as in the first analysis of the ATAC trial. RESULTS: DFS estimates at 4 years remained significantly more favorable (86.9% vs. 84.5%, respectively) for patients receiving anastrozole compared with those receiving tamoxifen (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.76-0.99; P = 0.03). The benefit generated by anastrozole in terms of DFS was even greater in patients with hormone receptor-positive tumors (HR, 0.82; 95% CI, 0.70-0.96; P = 0.014). The HR for TTR also indicated a significant benefit for patients receiving anastrozole compared with those receiving tamoxifen (HR, 0.83; 95% CI, 0.71-0.96; P = 0.015), with additional benefit for patients with hormone receptor-positive tumors (HR, 0.78; 95% CI, 0.65-0.93; P = 0.007). CLBC incidence data also continued to favor anastrozole (odds ratio [OR], 0.62; 95% CI, 0.38-1.02; P = 0.062), and statistical significance was achieved in the hormone receptor-positive subgroup (OR, 0.56; 95% CI, 0.32-0.98; P = 0.042). The updated safety analysis also confirmed the findings of the first analysis, in that endometrial cancer (P = 0.007), vaginal bleeding and discharge (P < 0.001 for both), cerebrovascular events (P < 0.001), venous thromboembolic events (P < 0.001), and hot flashes (P < 0.001) all occurred less frequently in the anastrozole group, whereas musculoskeletal disorders and fractures (P < 0.001 for both) continued to occur less frequently in the tamoxifen group. These results indicated that the safety profile of anastrozole remained consistent. CONCLUSIONS: After an additional follow-up period, anastrozole continues to show superior efficacy, which is most apparent in the clinically relevant hormone receptor-positive population. Furthermore, anastrozole has numerous noteworthy advantages in terms of tolerability compared with tamoxifen. These findings suggest that the benefits of anastrozole are likely to be maintained in the long term and provide further support for the status of anastrozole as a valid treatment option for postmenopausal women with hormone-sensitive early-stage breast cancer.

Anastrozole↗
PubMed2003

Anastrozole (Arimidex) versus tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: survival analysis and updated safety results.

We present an initial survival analysis and an update of the safety data of the North American and Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability (TARGET) double-blind, randomised, multicentre studies which compared anastrozole with tamoxifen as first-line treatment in postmenopausal patients with oestrogen receptor and/or progesterone receptor-positive (ER+/PR+) or receptor-unknown advanced breast cancer (ABC). At a median follow-up of 43.7 months, 56.0% of patients in the anastrozole group and 56.1% of patients in the tamoxifen group had died. The proportion of patients dead at 2 years was 31.1 and 32.0% in the anastrozole and tamoxifen groups, respectively. In the ER+/PR+ subgroup, 55.1 and 55.9% of patients had died and median time to deaths (TTD) were 40.8 and 41.3 months in the anastrozole and tamoxifen groups, respectively. Both agents remained well tolerated, with fewer reports of vaginal bleeding (anastrozole versus tamoxifen, 1.0% versus 2.5%) and thromboembolic events (anastrozole versus tamoxifen, 5.3% versus 9.0%) in the anastrozole group versus the tamoxifen group. Hot flushes and vaginal dryness were reported marginally less in the tamoxifen group compared with the Anastrozole group. Although no improvement in survival was observed, the favourable profile of anastrozole with respect to efficacy (TTP) and tolerability [Cancer 92 (2001) 2247] support the use of anastrozole in advance of tamoxifen as the first-line therapy choice in postmenopausal women with ABC.

Anastrozole↗
PubMed2003

Efficacy of tamoxifen following anastrozole ('Arimidex') compared with anastrozole following tamoxifen as first-line treatment for advanced breast cancer in postmenopausal women.

Anastrozole ('Arimidex') is indicated for the treatment of advanced breast cancer in postmenopausal women. Combined analysis of two international randomised, double-blind trials (n=1021) showed that in patients with hormone receptor-positive tumours, first-line treatment with anastrozole significantly prolonged the time to progression (TTP) compared with tamoxifen (median TTP: 10.7 versus 6.4 months, respectively; P=0.022). Second-line tamoxifen following anastrozole, or vice versa, in this trial population was unblinded. The treatments were crossed over and then efficacy was assessed using a questionnaire. Of 511 patients randomised to anastrozole, 137 (26.8%) received second-line tamoxifen. Questionnaire data were available for 119 patients; 58 (48.7%) gained clinical benefit (CB=complete+partial response (CR+PR)+(stable disease (SD) >/=24 weeks)), while 12 (10.1%) had an objective response (OR=CR+PR). Of 510 patients randomised to tamoxifen, 134 (26.3%) received second-line anastrozole. Questionnaire data from 95 patients showed that 54 (56.8%) gained CB and 7 of the patients gaining CB (7.4%) had an OR. Previous studies showed anastrozole is effective after first-line tamoxifen. These data show that the sequential administration of first-line anastrozole followed by tamoxifen provides effective use of these drugs in the treatment of postmenopausal women with advanced breast cancer.

Adult↗
PubMed2002

Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial.

PURPOSE: To compare the efficacy and tolerability of fulvestrant (formerly ICI 182,780) with anastrozole in the treatment of advanced breast cancer in patients whose disease progresses on prior endocrine treatment. PATIENTS AND METHODS: In this double-blind, double-dummy, parallel-group study, postmenopausal patients were randomized to receive either an intramuscular injection of fulvestrant 250 mg once monthly or a daily oral dose of anastrozole 1 mg. The primary end point was time to progression (TTP). Secondary end points included objective response (OR) rate, duration of response (DOR), and tolerability. RESULTS: Patients (n = 400) were followed for a median period of 16.8 months. Fulvestrant was as effective as anastrozole in terms of TTP (hazard ratio, 0.92; 95.14% confidence interval [CI], 0.74 to 1.14; P =.43); median TTP was 5.4 months with fulvestrant and 3.4 months with anastrozole. OR rates were 17.5% with both treatments. Clinical benefit rates (complete response + partial response + stable disease > or = 24 weeks) were 42.2% for fulvestrant and 36.1% for anastrozole (95% CI, -4.00% to 16.41%; P =.26). In responding patients, median DOR (from randomization to progression) was 19.0 months for fulvestrant and 10.8 months for anastrozole. Using all patients, DOR was significantly greater for fulvestrant compared with anastrozole; the ratio of average response durations was 1.35 (95% CI, 1.10 to 1.67; P < 0.01). Both treatments were well tolerated. CONCLUSION: Fulvestrant was at least as effective as anastrozole, with efficacy end points slightly favoring fulvestrant. Fulvestrant represents an additional treatment option for postmenopausal women with advanced breast cancer whose disease progresses on tamoxifen therapy.

Adult↗
PubMed2002

Phase III randomized trial of droloxifene and tamoxifen as first-line endocrine treatment of ER/PgR-positive advanced breast cancer.

PURPOSE: This trial was designed to demonstrate equivalence between droloxifene 40 mg/d and tamoxifen 20 mg/d as first-line treatment in pre- and post-menopausal women with ER+ and/or PgR+ advanced breast cancer based on time to disease progression and tumor response. MATERIALS AND METHODS: One thousand three hundred fifty four women with measurable disease, previously untreated by hormonal or chemotherapy for advanced or recurrent breast cancer, were enrolled by 179 institutions in 35 countries. Patients were stratified at baseline for menopausal status. Patients receiving adjuvant hormonal therapy within I year were excluded. All patients gave written informed consent, were randomized to 40mg droloxifene or 20 mg tamoxifen daily as single-agent therapy and underwent tumor assessment every 3 months. A central committee reviewed digitized images for all cases of tumor progression or objective response. RESULTS: The hazard ratio (droloxifene/tamoxifen) for the primary endpoint, time to disease progression, was 1.287 favoring tamoxifen (95% C.I.: 1.114-1.487; p <.001). The objective response rate (CR+PR) was 22.4% for droloxifene and 28.6% for tamoxifen (p = .02). Tamoxifen was superior to droloxifene overall, among both pre- and postmenopausal patients and among patients < or =65 years; there was no difference among women >65 years. The hazard ratio for all-cause mortality was 0.871 (95% C.I.: 0.672-1.129; p = .29), favoring droloxifene but not statistically significant. CONCLUSIONS: Droloxifene was significantly less effective than tamoxifen overall and particularly among women under 65 years. Tamoxifen and droloxifene were both less effective in pre-menopausal women with receptor-positive disease compared to post-menopausal women. Further clinical development of droloxifene was stopped.

Age Factors↗
PubMed2001

Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma.

BACKGROUND: Two randomized, double-blind trials have compared tamoxifen 20 mg daily and the selective, nonsteroidal aromatase inhibitor anastrozole 1 mg daily as first-line therapy for advanced breast carcinoma (ABC) in postmenopausal women. The trials were prospectively designed to allow for combined data analyses. METHODS: The combined study population included 1021 postmenopausal women (median age, 67 years [range, 30-92]) with ABC whose tumors were either estrogen and/or progesterone receptor positive or of unknown receptor status. Primary endpoints were time to progression (TTP), objective response, and tolerability. RESULTS: At a median duration of follow-up of 18.2 months, anastrozole was at least equivalent to tamoxifen in terms of median TTP (8.5 and 7.0 months, respectively; estimated hazard ratio [tamoxifen relative to anastrozole], 1.13 [lower 95% confidence level, 1.00]). In a retrospective subgroup analysis, anastrozole was superior to tamoxifen with respect to TTP (median values of 10.7 and 6.4 months for anastrozole and tamoxifen, respectively, two-sided P = 0.022) in patients with estrogen and/or progesterone receptor positive tumors (60% of combined trial population). In terms of objective response, 29.0% of anastrozole and 27.1% of tamoxifen patients achieved either a complete response (CR) or a partial response (PR). Clinical benefit (CR + PR + stabilization of > or = 24 weeks) rates were 57.1% and 52.0% for anastrozole and tamoxifen, respectively. Both anastrozole and tamoxifen were well tolerated. Anastrozole led to significantly fewer venous thromboembolic (P = 0.043; not adjusted for multiple comparisons) events, and vaginal bleeding was reported in fewer patients treated with anastrozole than with tamoxifen. CONCLUSIONS: In postmenopausal women with hormonally sensitive ABC, anastrozole should be considered as the new standard first-line treatment.

Adult↗
PubMed2001

Multicenter, Phase II study of capecitabine in taxane-pretreated metastatic breast carcinoma patients.

BACKGROUND: Capecitabine is an oral, tumor-targeted fluoropyrimidine carbamate with high activity in metastatic breast carcinoma and in paclitaxel-pretreated metastatic breast carcinoma. METHODS: The current multicenter, Phase II trial assessed the efficacy and safety of intermittent oral capecitabine, 1255 mg/m(2) twice daily (2 weeks of treatment followed by a 1-week rest period), in patients with metastatic breast carcinoma in whom prior taxane therapy had failed. All patients had failed treatment or had disease that was refractory to two or three previous chemotherapy regimens, one of which contained a taxane. Nearly all patients (96%) also had received prior anthracycline chemotherapy. Seventy-five patients were recruited at 5 centers, 74 of whom received treatment. RESULTS: The overall response rate was 26%, with response rates of 27% and 20%, respectively, in the subgroups of patients previously pretreated with paclitaxel (n = 47) or docetaxel (n = 27). The median survival was 12.2 months, the median duration of response was 8.3 months, and the median time to disease progression was 3.2 months. The most common treatment-related adverse events (all grades) were hand-foot syndrome (62%), diarrhea (58%), nausea (55%), emesis (37%), and stomatitis (34%). However, the majority were mild to moderate in intensity and only three patients experienced Grade 4 (according to the National Cancer Institute of Canada Common Toxicity criteria) adverse events. The only Grade 3 treatment-related adverse events reported in > or = 10% of the patients were hand-foot syndrome (22%), diarrhea (16%), and stomatitis (12%). Myelosuppression and alopecia were rare, and there were no reported treatment-related deaths. CONCLUSIONS: The results of the current study demonstrate that capecitabine is an effective and well tolerated treatment in patients with taxane-refractory or taxane-failing metastatic breast carcinoma. In addition, it is a convenient, orally administered drug, which makes it an attractive agent for use in outpatient treatment.

Administration, Oral↗
PubMed2001

Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate.

PURPOSE: To compare two doses of letrozole (0.5 mg and 2.5 mg every day) and megestrol acetate (40 mg qid) as endocrine therapy in postmenopausal women with advanced breast cancer previously treated with antiestrogens. PATIENTS AND METHODS: This double-blind, randomized, multicenter, multinational study enrolled 602 patients, all of whom were included in the primary analysis in the protocol. Patients had advanced or metastatic breast cancer with evidence of disease progression while receiving continuous adjuvant antiestrogen therapy, had experienced relapse within 12 months of stopping adjuvant antiestrogen therapy given for at least 6 months, or had experienced disease progression while receiving antiestrogen therapy for advanced disease. Tumors were required to be estrogen receptor- and/or progesterone receptor-positive or of unknown status. Confirmed objective response rate was the primary efficacy variable. Karnofsky Performance Status and European Organization for Research and Treatment of Cancer quality-of-life assessments were collected for 1 year. RESULTS: There were no statistically significant differences among the three treatment groups for overall objective tumor response. Patients treated with letrozole 0.5 mg had improvements in disease progression (P =.044) and a decreased risk of treatment failure (P =.018), compared with patients treated with megestrol acetate. Letrozole 0.5 mg showed a trend (P =.053) for survival benefit when compared with megestrol acetate. Megestrol acetate was more likely to produce weight gain, dyspnea, and vaginal bleeding, and the letrozole groups were more likely to experience headache, hair thinning, and diarrhea. CONCLUSION: Given a favorable tolerability profile, once-daily dosing, and evidence of clinically relevant benefit, letrozole is equivalent to megestrol acetate and should be considered for use as an alternative treatment of advanced breast cancer in postmenopausal women after treatment failure with antiestrogens.

Aged↗
PubMed2001

Phase I study of a third-generation selective estrogen receptor modulator, LY353381.HCL, in metastatic breast cancer.

PURPOSE: We conducted this phase I trial to determine the safety and toxicity profile of LY353381.HCl-a novel, potent, third-generation selective estrogen receptor modulator (SERM)-because this benzothiophene derivative demonstrated an SERM profile in preclinical studies. PATIENTS AND METHODS: We studied 32 patients with recurrent or metastatic breast cancer. Patients were treated in four cohorts with oral daily doses of 10, 20, 50, and 100 mg. Pharmacokinetic sampling was performed during the first 72 hours following the first dose on day 1 and during the 24 hours after the day 57 dose. Eligibility criteria included Eastern Cooperative Oncology Group performance status of 0 to 2; no significant major organ dysfunction; and at least 3 weeks elapsed since most recent hormonal therapy, chemotherapy, and estrogen replacement therapy. RESULTS: The median patient age was 56 years (range, 30 years to 76 years). The median number of prior chemotherapies for metastatic disease was one (range, zero to four), while the median number of prior hormone regimens for metastatic disease was two (range, zero to five). Receptor status was estrogen receptor (ER) positive and progesterone receptor (PR) positive, 19 patients; ER positive and PR negative, eight patients; ER positive and PR unknown, two patients; and ER and PR unknown, three patients. Dose-limiting toxicity was not observed. Treatment was well tolerated with mild to moderate hot flashes in 18 of 32 patients (56%) at all dose levels. Transvaginal ultrasound performed at baseline and after 12 weeks of treatment showed no endometrial thickening. Of the 32 patients evaluable for response, six patients had stable disease for at least 6 months with a median duration of 7.7 months (range, 6.2 months to 33.8 months). The pharmacokinetics of LY353381.HCl were generally linear with respect to time and studied dose range. CONCLUSION: As predicted in preclinical testing, daily oral LY353381.HCl is safe, is well tolerated at all tested dose levels, and may be clinically beneficial in patients with extensively pretreated metastatic breast cancer. Further studies with LY353381 to evaluate the efficacy in patients with or without prior exposure to tamoxifen and fewer overall prior regimens are under way.

Actuarial Analysis↗
PubMed2001

Are differences in the available aromatase inhibitors and inactivators significant?

Aromatase inhibitors are endocrine agents with a different mode of action than tamoxifen against breast tumors. In postmenopausal women, estrogen concentrations are maintained primarily via aromatase, a cytochrome P-450 enzyme that acts at the final step in the estrogen synthesis pathway. The first clinically available aromatase inhibitor, aminoglutethimide, was introduced for the second-line treatment of advanced breast cancer in the late 1970s. Despite proven efficacy in this setting, its widespread use was limited by its overall toxicity and its lack of selectivity for the aromatase enzyme. This led to the search for novel, more effective, and less toxic aromatase inhibitors. As a result, several aromatase inhibitors with a high degree of selectivity for aromatase and improved tolerability have become clinically available for the treatment of postmenopausal women with advanced breast cancer: (a) anastrozole; (b) letrozole; (c) fadrozole; (d) formestane; and (e) exemestane. Of these, formestane and exemestane are steroidal nonreversible aromatase inhibitors, also known as aromatase inactivators, whereas fadrozole, anastrozole, and letrozole are nonsteroidal reversible aromatase inhibitors. These agents differ in pharmacokinetics, selectivity, and potency, although all are more selective than aminoglutethimide. Some differences in adverse effect profile are also noticeable between and within these two classes of agents. The clinical significance of these differences is not yet evident but may well prove to be relevant in the long-term adjunctive setting.

Anastrozole↗
PubMed2000

Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group.

PURPOSE: The efficacy and tolerability of anastrozole (Arimidex; AstraZeneca, Wilmington, DE, and Macclesfield, United Kingdom) and tamoxifen were compared as first-line therapy for advanced breast cancer in 353 postmenopausal women. PATIENTS AND METHODS: The randomized, double-blind, multicenter study was designed to evaluate anastrozole 1 mg once daily relative to tamoxifen 20 mg once daily in patients with hormone receptor-positive tumors or tumors of unknown receptor status who were eligible for endocrine therapy. Primary end points were objective response (OR), defined as complete (CR) or partial (PR) response, time to progression (TTP), and tolerability. RESULTS: Anastrozole was as effective as tamoxifen in terms of OR (21% v 17% of patients, respectively), with clinical benefit (CR + PR + stabilization > or = 24 weeks) observed in 59% of patients on anastrozole and 46% on tamoxifen (two-sided P =.0098, retrospective analysis). Anastrozole had a significant advantage over tamoxifen in terms of TTP (median TTP of 11.1 and 5.6 months for anastrozole and tamoxifen, respectively; two-sided P =.005). The tamoxifen:anastrozole hazards ratio was 1.44 (lower one-sided 95% confidence limit, 1.16). Both treatments were well tolerated. However, thromboembolic events and vaginal bleeding were reported in fewer patients who received anastrozole compared with those who received tamoxifen (4.1% v 8.2% [thromboembolic events] and 1.2% v 3.8% [vaginal bleeding], respectively). CONCLUSION: Anastrozole satisfied the predefined criteria for equivalence to tamoxifen. Furthermore, we observed both a significant increase in TTP and a lower incidence of thromboembolic events and vaginal bleeding with anastrozole. These findings indicate that anastrozole should be considered as first-line therapy for postmenopausal women with advanced breast cancer.

Adult↗
PubMed2000

An overview of the use of non-steroidal aromatase inhibitors in the treatment of breast cancer.

A number of potent and selective non-steroidal aromatase inhibitors are now available for the treatment of advanced breast cancer in postmenopausal women. In particular, anastrozole represents a significant advantage over earlier agents, such as aminoglutethimide and formestane, in terms of both efficacy and tolerability. These agents are now established as the second-line therapy of choice in postmenopausal women with advanced disease progressing on tamoxifen and, furthermore, data are now available on the efficacy and tolerability of anastrozole as first-line treatment of advanced breast cancer compared with tamoxifen. The full potential of the new-generation aromatase inhibitors in the treatment of breast cancer is currently being investigated in a large programme of clinical trials, including evaluation as neoadjuvant treatment in postmenopausal women with newly-diagnosed locally-advanced or large operable breast cancers, as first-line treatment of advanced breast cancer in postmenopausal women. Aromatase inhibitors have been available for over 20 years; the ability of these compounds to reduce circulating oestradiol levels has been shown to produce clinical benefit in postmenopausal women with advanced breast cancer. Early aromatase inhibitors, however, such as aminoglutethimide and formestane, were not specific for the aromatase enzyme and resulted in significant side-effects.

Anastrozole↗
PubMed2000

Delphi-panel analysis of appropriateness of high-dose chemotherapy and blood cell or bone marrow autotransplants in women with breast cancer.

BACKGROUND: There is controversy whether high-dose chemotherapy and a blood cell or bone marrow autotransplant is a better treatment than conventional-dose chemotherapy for women with local/regional or metastatic breast cancer. Subject selection and time-to-treatment biases make definitive comparison impossible. Recent results of randomized trials are contradictory. OBJECTIVE: Determine appropriateness of high-dose chemotherapy and a blood cell or bone marrow autotransplant in women with breast cancer. PANELISTS: Nine breast cancer experts from diverse geographic sites and practice settings. EVIDENCE: Boolean MEDLINE searches of 'breast cancer' and 'chemotherapy' and/or 'blood cell' or 'bone marrow transplants'. PROCESS: We used a modified Delphi-panel group judgement process. Clinical variables were permuted to define 2058 clinical settings. Each panelist rated appropriateness of high-dose therapy and an autotransplant versus conventional therapy on a 9-point ordinal scale (1: most inappropriate, 9: most appropriate). An appropriateness index was developed based on median rating and amount of disagreement. The relationship of appropriateness indices to the permuted clinical variables was considered by analysis of variance and recursive partitioning. CONCLUSIONS: In women with local/regional breast cancer autotransplants were rated: 1) appropriate in those with > or = 10 cancer-involved lymph nodes; 2) uncertain in those with 4-9 cancer-involved nodes; and 3) inappropriate in women with < or = 3 cancer-involved lymph nodes. In women with metastatic breast cancer autotransplants were rated: 1) appropriate in those with metastases to 'favorable' sites (skin, lymph node, pleura) and a complete or partial response to chemotherapy; 2) uncertain in women with metastases to 'unfavorable' sites (lung, liver, or central nervous system) and a complete response to chemotherapy or those with bone metastases and a complete or partial response or stable disease after chemotherapy; and 3) inappropriate in other settings.

Antineoplastic Agents↗
PubMed2000

Exemestane in advanced breast cancer.

Exemestane is an orally active steroidal aromatase inhibitor that has demonstrated efficacy in the treatment of postmenopausal patients with advanced breast cancer. This compound exhibits a good tolerability and safety profile, which may result from its highly selective mechanism of action. Exemestane binds irreversibly to the aromatase enzyme causing inactivation of the enzyme. This irreversible loss of enzyme may contribute to the sustained inhibition of estrogen synthesis noted following exemestane administration. Exemestane is a potent inhibitor of aromatization reducing estrogen synthesis in vivo by greater than 97%. The recommended dose of exemestane is 25 mg once daily. Although dosages up to 600 mg/day have been tested, the maximum tolerated dose of exemestane has not been reached in clinical study. The most frequently reported drug-related adverse events are hot flushes, nausea and fatigue, which are consistent with the estrogen-suppressive effects of the drug. Discontinuation due to adverse events is rare. Exemestane is a safe and well-tolerated alternative for the treatment of postmenopausal patients with advanced breast cancer.

Androstadienes↗
PubMed2000

A retrospective study of first indicators of breast cancer recurrence.

This study was performed to evaluate the first indicators of breast cancer recurrence in 1,145 patients treated at the University of Texas MD Anderson Cancer Center, between July 1973 and December 1980. Twenty patients were excluded due to incomplete data, resulting in a total number of 1,125 evaluable patients. Data collection included the first metastatic site and its means of detection (symptoms, self-examination, physical examination performed by a physician, and the results of blood and radiological tests). Whether recurrence was found at the scheduled follow-up visits or between the scheduled visits was also analyzed. Symptoms were the primary indicator of relapse for 648 cases (57.6% of the study population). An additional 361 cases (32.1% of the total group) were detected by self-examination or by physician-performed physical examination. Other investigations, e.g. bone scans, liver scans, chest X-rays, and blood tests, revealed recurrent disease in only 116 patients (10. 3% of the population). Among the 1,125 patients, 254 recurrences (22. 6% of the study population) were detected at the scheduled follow-up surveillance and, among these, 64.6% were found by history or physical examination. The distribution of metastatic sites and first indicators of metastases remained constant over time. The scheduled follow-up visits detected a mean of 25.9% of relapses during the first 36 months, while after 36 months only 16.3% of relapses were detected by systematic monitoring. There were no statistically significant differences in disease-free overall survival rates between symptomatic and asymptomatic patients at the time the first recurrence was detected. Moreover, the disease-free and overall survival rates appeared to be the same in symptomatic and asymptomatic patients, whether or not the recurrence was detected by a scheduled follow-up examination. Two conclusions emerged from the present study. Extensive, routine laboratory investigations are not justifiable following curative treatment of primary breast cancer, and it seems reasonable and cost-effective to reduce follow-up surveillance to careful history and physical examination only. The actual method of surveillance does not significantly affect the time interval to metastasis detection and seems inefficient. Clearly, more sensitive methods are needed for earlier detection of recurrent metastatic breast cancer. In addition, early detection of metastases would be even more valuable if more effective treatment modalities of recurrent or metastatic breast cancer were available.

Bone Neoplasms↗
PubMed1999

Static disease on anastrozole provides similar benefit as objective response in patients with advanced breast cancer.

BACKGROUND: This paper reports on the clinical relevance of durable static disease (SD) (> or = 24 weeks) in breast cancer patients treated with the aromatase inhibitor anastrozole. PATIENTS AND METHODS: All patients were part of two prospective, randomised, multicentre studies in postmenopausal women with advanced disease in which megestrol acetate was compared with anastrozole 1 mg. Survival from initiation of treatment was analysed by the response type, i.e., complete response (CR)/partial response (PR), static disease (SD) (> or = 24 weeks), or progressive disease (PD), achieved on therapy. RESULTS: Median survival with anastrozole 1 mg was similar between patients who obtained CR/PR and SD (> or = 24 weeks). Similarly, no difference in survival was observed in patients treated with megestrol acetate who achieved CR/PR and SD. With both treatments patients with CR/PR and SD had improved survival over those patients with PD within 24 weeks. There was no difference between treatment arms for patients showing PD within 24 weeks. CONCLUSIONS: These data confirm that durable SD (> or = 24 weeks) is a clinically useful remission criterion in postmenopausal women with advanced breast cancer with predictive value for overall survival. It also confirms the value of this endpoint with anastrozole, a new generation aromatase inhibitor.

Anastrozole↗