No abstract

PURPOSE We compared the endocrine effects of 6 and 12 months of adjuvant letrozole versus tamoxifen in postmenopausal patients with hormone-responsive early breast cancer within an ongoing phase III trial. PATIENTS AND METHODS Patients were randomly assigned to receive tamoxifen, letrozole, or letrozole plus zoledronic acid. Serum values of estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone-sulphate (DHEA-S), progesterone, and cortisol were measured at baseline and after 6 and 12 months of treatment. For each hormone, changes from baseline at 6 and 12 months were compared between treatment groups, and differences over time for each group were analyzed. Results Hormonal data were available for 139 postmenopausal patients with a median age of 62 years, with 43 patients assigned to tamoxifen and 96 patients assigned to letrozole alone or combined with zoledronic acid. Baseline values were similar between the two groups for all hormones. Many significant changes were observed between drugs and for each drug over time. Namely, three hormones seemed significantly affected by one drug only: estradiol that decreased and progesterone that increased with letrozole and cortisol that increased with tamoxifen. Both drugs affected FSH (decreasing with tamoxifen and slightly increasing with letrozole), LH (decreasing more with tamoxifen than with letrozole), testosterone (slightly increasing with letrozole but not enough to differ from tamoxifen), and DHEA-S (increasing with both drugs but not differently between them). Zoledronic acid did not have significant impact on hormonal levels. CONCLUSION Adjuvant letrozole and tamoxifen result in significantly distinct endocrine effects. Such differences can explain the higher efficacy of letrozole as compared with tamoxifen.

NCT00331097.

The aim of the study was to demonstrate the superiority of docetaxel and epirubicin vs docetaxel alone as first-line therapy in metastatic breast cancer patients pretreated with adjuvant or neoadjuvant epirubicin. We compared single agent docetaxel 100 mg m À2 (D) with the combination of docetaxel 80 mg m À2 and epirubicin 75 mg m À2 (ED). The response rate (72 vs 79%), the progression-free survival (median 9 vs 11 months) and the overall survival (median 18 vs 21 months) were not significantly different between the ED (n ¼ 26) and D arms (n ¼ 25), respectively. Leucopaenia, nausea and stomatitis were significantly worse with ED. In conclusion, epirubicin should not be administered in combination with taxanes in metastatic breast cancer patients relapsed after an anthracycline-based adjuvant or neoadjuvant therapy. Anthracyclines are among the most active agents in the treatment of metastatic and adjuvant breast cancer (Fossati et al, 1998; EBCTCG, 2004). Docetaxel is the only agent that has demonstrated survival benefits in anthracycline-resistant patients (Nabholtz et al, 1999) and superior activity over doxorubicin as first-line chemotherapy in patients previously treated with alkylating agents (Chan et al, 1999). Owing to its activity and to the lack of crossresistance with anthracyclines, there is a strong rationale for combining docetaxel with anthracyclines. The anthracyclinetaxane regimens can now be considered the most effective regimens in metastatic breast cancer (MBC) and a first-line therapy of choice in this set of patients (Valero and Hortobagyi, 2003). In particular, many reports have described the combined use of docetaxel and epirubicin, an anthracycline less cardiotoxic than doxorubicin, with the objective to find the safest and most efficient way to integrate these classes of drugs (Mavroudis et al, 2000;Pagani et al, 2000). However, whether an anthracyclinetaxane regimen is worthy as first-line treatment for MBC patients pretreated with adjuvant or neoadjuvant anthracyclines is an open question, not definitely assessed by appropriate prospective trials. Therefore, we planned a randomised phase III trial to compare epirubicin and docetaxel vs docetaxel alone for efficacy and safety as first-line chemotherapy of MBC patients pretreated with epirubicin in adjuvant or neoadjuvant setting. MATERIALS AND METHODSEligibility criteria were: women with MBCp65 years; no previous chemotherapy for metastatic disease; measurable disease; Eastern Cooperative Oncology Group (ECOG) performance status of 0 -2; previous adjuvant or neoadjuvant chemotherapy with anthracyclines, up to a total dose of doxorubicin p250 mg m À2 or epirubicin p500 mg m À2 , completed at least 12 months before enrollment; absence of brain metastases; adequate bone marrow, renal and liver function; left ventricular ejection fraction (LVEF) X50%. Previous adjuvant endocrine therapy as well as endocrine therapy for metastatic disease were allowed. Patients were excluded if they had received taxanes as adjuvant chemotherapy or had histo...

Background: Few data are available on compliance and safety of adjuvant chemotherapy when indicated in elderly breast cancer patients; CMF (cyclophosphamide, methotrexate, fluorouracil) can be reasonably considered the most widely accepted standard of treatment.