Double-blind randomised trial comparing the non-steroidal aromatase inhibitors letrozole and fadrozole in postmenopausal women with advanced breast cancer.

BACKGROUND: To compare the efficacy, safety and tolerability of letrozole, an advanced non-steroidal aromatase inhibitor, and fadrozole hydrochloride, an older-generation drug in this class, we conducted a randomised double-blind trial in postmenopausal women with advanced breast cancer. PATIENTS AND METHODS: One hundred and fifty-seven postmenopausal women with advanced breast cancer were enrolled and randomly assigned to receive letrozole or fadrozole in a multicentre, randomised double-blind trial in Japan. One hundred and fifty-four eligible patients were treated with either letrozole 1.0 mg once daily (n = 77) or fadrozole 1.0 mg twice daily (n = 77), for a minimum of 8 weeks. RESULTS: Letrozole showed a significantly higher overall objective response rate [complete response (CR) + partial response (PR)] than fadrozole (31.2% and 13.0%, respectively; P = 0.011, Fisher's exact test). Clinical benefits defined as CR, PR and stable disease (no change in status for more than 24 weeks) were also higher in patients treated with letrozole (50.6%) than fadrozole (35.1%). Letrozole was significantly superior to fadrozole in terms of the dominant lesion in soft tissue, bone and viscera (P = 0.011, stratified Mantel-Haenszel test). Median time to progression was 211 days in the letrozole group and 113 days in the fadrozole group with no significant difference (P = 0.175, log-rank test). Letrozole markedly reduced the estradiol, estrone and estrone sulfate levels in peripheral blood within 4 weeks. The suppressive effect of fadrozole on these hormone levels was insufficient. Adverse drug reactions were observed in 35.9% of the patients treated with letrozole and in 39.5% of those treated with fadrozole with no significant difference between the two groups (P = 0.74, Fisher's exact test). Most of the adverse drug reactions were rated as grade 1 or 2. CONCLUSIONS: The results show letrozole at a dose of 1.0 mg once daily to be more effective in treating postmenopausal women with advanced breast cancer than fadrozole at 1.0 mg twice daily, with similar safety and tolerability profiles.     

A study of fadrozole, a new aromatase inhibitor, in postmenopausal women with advanced metastatic breast cancer.

PURPOSE: The study investigated the therapeutic effects of fadrozole (CGS 16949A), a new aromatase inhibitor, in women who had received prior treatment for metastatic breast cancer. MATERIALS AND METHODS: Eighty postmenopausal women who had received prior treatment for metastatic breast cancer were randomized to receive fadrozole 1 mg/d or 4 mg/d per day orally. Seventy-eight patients were assessable for toxicity and response. RESULTS: Toxicity was limited to mild (grade 1) to moderate (grade 2) hot flashes in 28%, nausea and vomiting in 13%, fatigue in 8%, and mild loss of appetite in 5% of patients. No electrolyte or unanticipated hormonal changes occurred. The overall response was 23% (complete response, 10%; partial response, 13%). In addition, 45% of the patients had a no change status. There was no difference in response rate between the patients randomized to the two different doses of fadrozole. Only dominant site of metastases significantly affected response. The median time to treatment failure (TTF) was 4.4 months (4.7 months on 1 mg/d and 3.7 months on 4 mg/d). The median survival was 22.6 months (17.5 months on 1 mg/d; median survival has not been reached in patients on 4 mg/d). The response and survival in patients with estrogen receptor (ER)-positive and ER-unknown disease were not significantly different. CONCLUSIONS: Fadrozole has good therapeutic effect as a second-line treatment in postmenopausal women with metastatic breast cancer. In this study there was no significant difference in toxicity or response between 1 mg/d and 4 mg/d. Further trials comparing fadrozole to other hormone treatment are indicated.     

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.     

Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study.

PURPOSE: To compare the efficacy and tolerability of anastrozole (Arimidex; AstraZeneca, Wilmington, DE, and Macclesfield, United Kingdom) with that of tamoxifen as first-line therapy for advanced breast cancer (ABC) in postmenopausal women. PATIENTS AND METHODS: This randomized, double-blind, multicenter study evaluated the efficacy of anastrozole 1 mg once daily relative to tamoxifen 20 mg once daily in patients with tumors that were hormone receptor-positive or of unknown receptor status who were eligible for endocrine therapy. The primary end points were time to progression (TTP), objective response (OR), and tolerability. RESULTS: A total of 668 patients (340 in the anastrozole arm and 328 in the tamoxifen arm) were randomized to treatment and followed-up for a median of 19 months. Median TTP was similar for both treatments (8.2 months in patients who received anastrozole and 8.3 months in patients who received tamoxifen). The tamoxifen:anastrozole hazards ratio was 0.99 (lower one-sided 95% confidence limit, 0.86), demonstrating that anastrozole was at least equivalent to tamoxifen. Anastrozole was also as effective as tamoxifen in terms of OR (32.9% of anastrozole and 32.6% of tamoxifen patients achieved a complete response [CR] or partial response [PR]). Clinical benefit (CR + PR + stabilization of > or = 24 weeks) rates were 56.2% and 55.5% for patients receiving anastrozole and tamoxifen, respectively. Both treatments were well tolerated. However, incidences of thromboembolic events and vaginal bleeding were reported in fewer patients treated with anastrozole than with tamoxifen (4.8% v 7.3% [thromboembolic events] and 1.2% v 2.4% [vaginal bleeding], respectively). CONCLUSION: Anastrozole satisfied the predefined criteria for equivalence to tamoxifen. Together with the lower observed incidence of thromboembolic events and vaginal bleeding, these findings indicate that anastrozole should be considered as first-line therapy for postmenopausal women with ABC.     

Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group.

PURPOSE: To compare the efficacy and tolerability of tamoxifen with that of letrozole, an oral aromatase inhibitor, with tamoxifen as first-line therapy in postmenopausal women with advanced breast cancer. PATIENTS AND METHODS: Nine hundred seven patients were randomly assigned letrozole 2.5 mg once daily (453 patients) or tamoxifen 20 mg once daily (454 patients). Patients had estrogen receptor- and/or progesterone receptor-positive tumors, or both receptors were unknown. Recurrence during adjuvant antiestrogen therapy or within the following 12 months or prior endocrine therapy for advanced disease precluded enrollment. One prior chemotherapy regimen for metastatic disease was allowed. The primary end point was time to progression (TTP). Secondary end points included overall objective response rate (ORR), its duration, rate and duration of clinical benefit, time to treatment failure (TTF), overall survival, and tolerability. RESULTS: TTP was significantly longer for letrozole than for tamoxifen (median, 41 v 26 weeks). Treatment with letrozole reduced the risk of progression by 30% (hazards ratio, 0.70; 95% confidence interval, 0.60 to 0.82, P =.0001). TTP was significantly longer for letrozole irrespective of dominant site of disease, receptor status, or prior adjuvant antiestrogen therapy. Similarly, TTF was significantly longer for letrozole (median, 40 v 25 weeks). ORR was higher for letrozole (30% v 20%; P =.0006), as was the rate of clinical benefit (49% v 38%; P =.001). Survival data are currently immature and not reported here. Both treatments were well tolerated. CONCLUSION: Letrozole was significantly superior to tamoxifen in TTP, TTF, ORR, and clinical benefit rate. Our results support its use as first-line endocrine therapy in postmenopausal women with advanced breast cancer.     

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.     

High dose toremifene (240 mg daily) is effective as first line hormonal treatment in advanced breast cancer an ongoing phase II multicenter Finnish-Latvian cooperative study

The efficacy of high dose toremifene (240 mg daily) in postmenopausal women with advanced breast cancer is investigated in this ongoing study. At present, 38 patients are fully evaluable. Ten patients have CR (26%), 16 PR (42%) (objective response rate 68%), 8 NC (21%), and 4 PD (11%). Most objective responses are in soft tissue tumors (14/17, 82%). The response rate is equally high in patients with positive or unknown estrogen receptor (ER) status. Median duration of responses and survival are not yet evaluable. Of 48 patients evaluable for side-effects, 22 (46%) experienced some kind of toxicity, which was mild in 64% of cases, moderate in 29%, and mostly of estrogenic type. The study will continue to confirm the results thus far obtained.     

Clinical trial of fadrozole hydrochloride for postmenopausal patients with recurrent breast cancer]

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.     

Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group.

PURPOSE: To analyze overall survival (OS) and update efficacy data for letrozole versus tamoxifen as first-line therapy in postmenopausal women with locally advanced or metastatic breast cancer. PATIENTS AND METHODS: This multicenter phase III trial randomly assigned 916 patients with hormone receptor-positive or unknown tumors letrozole 2.5 mg (n = 458) or tamoxifen 20 mg (n = 458) daily until disease progression. Optional cross-over was permitted at the treating physician's discretion. This report updates efficacy at a median follow-up of 32 months. RESULTS: The superiority of letrozole to tamoxifen was confirmed for time to progression (median, 9.4 v 6.0 months, respectively; P <.0001), time to treatment failure (median, 9 v 5.7 months, respectively; P <.0001), overall objective response rate (32% v 21%, respectively; P =.0002), and overall clinical benefit. Median OS was slightly prolonged for the randomized letrozole arm (34 v 30 months, respectively). Although this difference in OS is not significant, survival was improved in the randomized letrozole arm over the first 2 years of the study. Approximately one half of the patients in each arm crossed over. Total duration of endocrine therapy ("time to chemotherapy") was significantly longer (P =.005) for patients initially on letrozole (median, 16 months) than for patients initially on tamoxifen (median, 9 months). Time to worsening of Karnofsky performance score was significantly delayed with letrozole compared with tamoxifen (P =.001). CONCLUSION: This study documents the superiority of letrozole over tamoxifen in first-line endocrine therapy in postmenopausal women with advanced breast cancer.     

First-line fadrozole HCI (CGS 16949A) versus tamoxifen in postmenopausal women with advanced breast cancer: Prospective randomised trial of the Swiss Group for Clinical Cancer Research SAKK 20/88

BACKGROUND:: In a phase III randomized trial, we compared the effectivenessand tolerability of fadrozole (CGS 16949A), a non-steroidalaromatase inhibitor, to tamoxifen as first-line endocrine therapyin postmenopausal women with advanced breast cancer. PATIENTS AND METHODS:: Two hundred twelve eligible patients were randomized to receivetamoxifen 20 mg daily, or fadrozole 1 mg twice daily orallyuntil disease progression or the advent of undue toxicity. Thetreatments were to be discontinued upon disease progression. RESULTS:: Prognostic factors were well balanced between the treatmentgroups, except for sites of metastatic disease. Fadrozole-treatedpatients had significantly more visceral, especially liver,involvement and less bone-dominant disease. Response rates forfadrozole and tamoxifen were similar, 20% and 27% (95% ConfidenceLimits (CL): 13%–29% and 21%–35%), respectively.Time to treatment failure was longer in patients randomizedto tamoxifen (8.5 months for tamoxifen vs. 6.1 months for fadrozole),but did not reach statistical significance after adjustmentfor prognostic factors (P=0.09). Fadrozole, for which a significantlylower percentage of clinically relevant toxic effects (WHO toxicitygrade     

Idoxifene versus tamoxifen: a randomized comparison in postmenopausal patients with metastatic breast cancer.

BACKGROUND: More efficacious and safer hormonal agents are needed for breast cancer treatment and prevention. Idoxifene is a novel selective estrogen receptor modulator (SERM) that, in preclinical models, has greater antiestrogenic but lower estrogenic activity than tamoxifen. PATIENTS AND METHODS: Three hundred and twenty-one postmenopausal patients with hormone receptor-positive or -unknown metastatic breast cancer were randomized to receive either tamoxifen or idoxifene as initial endocrine therapy for advanced disease. Data were analyzed based on intention to treat and all the responses were subject to independent review. RESULTS: At the time of a second planned interim analysis, the trial was stopped for economic considerations, not for reasons related to safety or efficacy. Complete data for the 219 patients included in the second interim analysis are fully available and reported here. Median age was 59.1 years for idoxifene patients and 59.9 years for tamoxifen patients. Complete response (CR) plus partial response (PR) rates were as follows: tamoxifen, 9%; idoxifene, 13% (P = 0.39). Clinical benefit rate [CR + PR + stable disease (SD) >or=6 months] was 34.3% for idoxifene and 38.7% for tamoxifen (P = 0.31). Median time to progression and duration of response were 140 days and 151.5 days, respectively, for tamoxifen compared with 166 days and 218 days for idoxifene. None of these endpoints was significantly different for the two drugs, nor was survival. Adverse events (lethal, serious but not lethal and important but not life threatening) were similar in the two arms. CONCLUSIONS: Idoxifene was both active and well tolerated in postmenopausal women with metastatic breast cancer. Idoxifene had similar efficacy and toxicity to tamoxifen in this randomized comparison.     

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.     

Advanced breast cancer in Egyptian women: clinical features and response to endocrine therapy. The Anglo-Egyptian Health Agreement Collaborative Study.

Response to endocrine therapy and its relationship to the clinical features of the disease were studied in 84 Egyptian patients with inoperable, locally advanced or metastatic breast cancer. Twenty-four premenopausal patients were treated by oophorectomy with or without concurrent prednisolone. Only one of 20 evaluable patients achieved an objective response. Median time to progression for premenopausal patients was 3 months. Sixty postmenopausal patients received tamoxifen 10 mg twice daily either alone or with prednisolone. Fourteen of 57 (25%) evaluable patients achieved an objective response (four complete remission, 10 partial remission). Median duration of response was 13 months and median time to progression for all postmenopausal patients was 5 months (range 1-30 months). The outcome for postmenopausal patients was similar to that found in a parallel study at Guy's Hospital, London. The response rate for premenopausal Egyptian patients was, however, disappointing and lends support to the claim that breast cancer in Egyptian women is particularly aggressive.     

Exemestane improves survival in metastatic breast cancer: results of a phase III randomized study

We compared the efficacy and safety of the oral aromatase inactivator exemestane (EXE) with megestrol acetate (MA) in women with metastatic breast cancer. This phase III randomized, double-blind, multicenter study was conducted in 769 postmenopausal women who had experienced tamoxifen failure. Treatment arms consisted of EXE 25 mg once daily (n=366) or MA 40 mg four times daily (160 mg daily; n=403). Peer-reviewed, intent-to-treat analyses demonstrated that EXE induced a trend toward higher rates of complete response (CR)+partial response (PR) (15.0% vs. 12.4%) and of CR+PR+stable disease (SD)=24 weeks (37.4% vs. 34.6%), but differences were not statistically significant. Statistically significant differences favoring EXE were seen in median duration of CR+PR+SD=24 weeks (60.1 vs. 49.1 weeks; P=0.025), time to tumor progression (20.3 vs. 16.6 weeks; P=0.037), time to treatment failure (16.3 vs. 15.7 weeks; P=0.042), and overall survival (not reached vs. 123.4 weeks; P=0.039). Both treatments were well tolerated, but MA was associated with more grade 3 or 4 weight gain (8% vs. 17%, P=0.001); the pain score was sim-ilar in both groups. There was a trend toward superiority in treatment-related signs and symptoms (TRSS) with EXE. There was greater improvement in the pain score and TRSS in patients achieving an objective response with EXE vs. MA. Quality of life improved or was similar for EXE in most domains. Exemestane offers an important new treatment option for postmenopausal women with hormone-responsive breast cancer.     

CGS20267 (Letrozole), a new aromatase inhibitor: late phase II study for postmenopausal women with advanced or recurrent breast cancer (no. 1)--investigation of recommended clinical dose CGS20267 Study Group

To determine the recommended clinical dose of CGS20267 (Letrozole), we conducted a randomized comparative study as a late phase II study (first part) in postmenopausal women with advanced or recurrent breast cancer. Forty-one patients were randomly assigned to receive 0.5 mg or 1.0 mg once daily. There were no statistically significant differences in background between the two groups. Although there was no significant difference in the objective response rates between the two groups, the rate was higher at 1.0 mg (44.4%) than at 0.5 mg (38.1%). We also combined these data with the results of an early phase II study. The objective response rates (CR + PR) were 31.4% at 0.5 mg and 42.2% at 1.0 mg, and response rates consisting of CR, PR, and NC for longer than 6 months were significantly higher at a dose of 1.0 mg (68.9%) than 0.5 mg (41.2%). Side effects included drug-related adverse events in 36.8% at 0.5 mg and in 31.6% at 1.0 mg. All of the events were grade 2 or lower, indicating a favorable tolerability of CGS20267. These results demonstrated that CGS20267 1.0 mg once daily is more effective than 0.5 mg, and has comparable safety, in the treatment of postmenopausal women with advanced or recurrent breast cancer. We conclude the recommended clinical dose of CGS20267 should be 1.0 mg once daily.     

Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment.

PURPOSE: To compare the efficacy and tolerability of fulvestrant (formerly ICI 182,780) and anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. PATIENTS AND METHODS: Patients (n = 451) with advanced breast cancer were randomized to receive fulvestrant 250 mg as a once-monthly (one x 5 mL) intramuscular injection or an oral dose of anastrozole 1 mg in this open, parallel-group, multicenter trial. The primary end point was time to progression (TTP). Secondary end points included objective response (OR) rates, defined as complete response (CR) or partial response (PR), duration of response (DOR), and tolerability. RESULTS: Patients were followed for a median period of 14.4 months. In terms of TTP, fulvestrant was as effective as anastrozole (hazard ratio, 0.98; confidence interval [CI], 0.80 to 1.21; P =.84). Median TTP was 5.5 months for fulvestrant and 5.1 months for anastrozole. OR rates showed a numerical advantage for fulvestrant (20.7%) over anastrozole (15.7%) (odds ratio, 1.38; CI, 0.84 to 2.29; P =.20). Clinical benefit rates (CR + PR + stable disease > or = 24 weeks) were 44.6% for fulvestrant and 45.0% for anastrozole. Median DOR was 14.3 months for fulvestrant and 14.0 months for anastrozole. Both treatments were well tolerated, with 3.2% and 1.3% of fulvestrant- and anastrozole-treated patients, respectively, withdrawn from treatment because of an adverse event. CONCLUSION: Fulvestrant was as effective as anastrozole. These data confirm that fulvestrant is an additional, effective, and well-tolerated treatment for advanced breast cancer in postmenopausal women whose disease progressed on prior endocrine therapy.     

Efficacy of first-line letrozole versus tamoxifen as a function of age in postmenopausal women with advanced breast cancer

PURPOSE: To compare the efficacy, in regard to time to progression (TTP) and objective response rate (ORR), of letrozole (Femara; Novartis Pharma AG; Basel Switzerland), an oral aromatase inhibitor, with that of tamoxifen (Tamofen; Leiras OY; Turku, Finland) as first-line therapy in younger (<70 years) and older (>/=70 years) postmenopausal women with advanced breast cancer. MATERIALS AND METHODS: Nine hundred seven patients with advanced breast cancer were randomly assigned to receive 2.5 mg letrozole (n = 453) or 20 mg tamoxifen (n = 454) once daily in a double-blind, multicenter, international trial. Among the prospectively planned analyses were analyses of TTP and ORR by age (<70 and >/=70 years). The results of these prospectively planned analyses are reported here. RESULTS: Letrozole was as effective in older postmenopausal women (>/=70 years of age) as it was in younger postmenopausal women (<70 years of age). The overall ORR in the older subgroup was significantly higher in patients treated with letrozole (38%) than in patients treated with tamoxifen (18%). In the younger subgroup of postmenopausal patients, the ORRs were not significantly different (letrozole, 26%; tamoxifen, 22%). TTP was significantly longer for letrozole than for tamoxifen in both age groups (younger: letrozole median TTP, 8.8 months; tamoxifen, 6.0 months; older: letrozole median TTP, 12.2 months; tamoxifen, 5.8 months). Although age was independently prognostic of TTP, there was no significant effect of age on ORR in the presence of other factors. CONCLUSION: The data show that letrozole, 2.5 mg once daily, is as effective in older, postmenopausal women as it is in younger postmenopausal women with advanced breast cancer. In addition, letrozole was more effective than tamoxifen in both younger and older patients.     

Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study

Background:A randomized, double-blind, multicenter studywas conducted to compare the anti-tumor activity of letrozole vs.tamoxifen in postmenopausal women with ER and/or PgR positive primaryuntreated breast cancer. Patients and methods:Threehundred thirty-seven postmenopausal women with ER and/or PgR positiveprimary untreated breast cancer were randomly assigned once dailytreatment with either letrozole 2.5 mg or tamoxifen 20 mg for fourmonths. At baseline none of the patients were considered to becandidates for breast-conserving surgery (BCS) and 14% ofthe patients were considered inoperable. The primary endpoint was tocompare overall objective response (CR + PR) determined by clinicalpalpation. Secondary endpoints included overall objective response onultrasound and mammography and the number of patients who qualified forBCS. Results:Overall objective response rate (clinicalpalpation) was statistically significantly superior in the letrozolegroup, 55% compared to tamoxifen, 36% (P<0.001). Secondary endpoints of ultrasound response, 35% vs.25% (P= 0.042), mammographic response, 34% vs.16% (P< 0.001), and BCS, 45% vs. 35%(P= 0.022) between the letrozole and tamoxifen groups,respectively, showed letrozole to be significantly superior. Bothtreatments were well tolerated. Conclusions:This studyshows that letrozole is more effective than tamoxifen as preoperativetherapy in postmenopausal patients with ER and/or PgR positive primaryuntreated breast cancer and is at least as well tolerated.     

Megestrol acetate therapy for advanced breast cancer

One hundred twenty-four patients with metastatic breast cancer were treated with 40 mg of megestrol acetate four times daily. Complete responses (CR) or partial responses (PR) were seen in 29 patients (23%). CR, PR, or stable disease (S) was seen in 80 patients (65%). The median duration of response was 22 months for CR and PR and ten months for S. A significantly higher response rate (CR + PR) was seen in estrogen-receptor-positive (ER-positive) patients (26%) and in patients who had not received prior therapy (39%). A significant relationship to response could not be established for menopausal status, progesterone-receptor (PrR) status, dominant site of disease, or prior administration of chemotherapy. Median survival was 66+ months for responders, 35 months for patients with stable disease, and 9 months for nonresponders. These differences are all statistically significant (P less than .001). Toxicity was minimal, and side effects consisted primarily of weight gain, which was seen in 18 patients (14.5%). Megestrol acetate can provide effective palliation in patients with advanced breast cancer.     

Tamoxifen and alpha interferon in advanced breast cancer.

Thirteen pretreated advanced breast cancer patients received a combination of alpha interferon 5 million IU every 2 days, subcutaneously, plus tamoxifen 10 mg 3 times daily, until disease progression. The objective response rate was 15.4%: 1 patient achieved a complete response, 1 a partial response and 11 demonstrated stable disease; half of the patients were receptor negative and/or pretreated with hormonotherapy. Durations of response were 16 and 26 months for the CR and PR patients respectively; median progression-free survival was 4 months (range 0-26). Toxicities were registered according to WHO criteria: 4 patients stopped the treatment with interferon because of severe flu-like symptoms, while in the others the combination was generally accepted with good tolerance.