Weekly docetaxel versus CMF as adjuvant chemotherapy for older women with early breast cancer: final results of the randomized phase III ELDA trial.

BACKGROUND: Evidence on adjuvant chemotherapy in older women with breast cancer is poor. We tested whether weekly docetaxel is more effective than standard chemotherapy. PATIENTS AND METHODS: We carried out a multicenter, randomized phase III study. Women aged 65-79, operated for breast cancer, with average to high risk of recurrence, were allocated 1 : 1 to CMF (cyclophosphamide 600 mg/m², methotrexate 40 mg/m², fluorouracil 600 mg/m², days 1, 8) or docetaxel (35 mg/m(2) days 1, 8, 15) every 4 weeks, for four or six cycles according to hormone receptor status. Primary end point was disease-free survival (DFS). A geriatric assessment was carried out. Quality of life (QoL) was assessed with EORTC C-30 and BR-23 questionnaires. RESULTS: From July 2003 to April 2011, 302 patients were randomized and 299 (152 allocated CMF and 147 docetaxel) were eligible. After 70-month median follow-up, 109 DFS events were observed. Unadjusted hazard ratio (HR) of DFS for docetaxel versus CMF was 1.21 [95% confidence interval (CI) 0.83-1.76, P = 0.32]; DFS estimate at 5 years was 0.69 with CMF and 0.65 with docetaxel. HR of death was 1.34 (95% CI 0.80-2.22, P = 0.26). There was no interaction between treatment arms and geriatric scales measuring patients' ability or comorbidities. Hematological toxicity, mucositis and nausea were worse with CMF; allergy, fatigue, hair loss, onychopathy, dysgeusia, diarrhea, abdominal pain, neuropathy, cardiac and skin toxicity were worse with docetaxel. One death was attributed to CMF and two to docetaxel. Increasing age, impairment in instrumental daily living activities, number of comorbidities and docetaxel treatment were independently associated with severe nonhematological toxicity. QoL was worse with docetaxel for nausea-vomiting, appetite loss, diarrhea, body image, future perspective, treatment side-effects and hair loss items. CONCLUSIONS: Weekly docetaxel is not more effective than standard CMF as adjuvant treatment of older women with breast cancer and worsens QoL and toxicity. CLINICALTRIALSGOV: NCT00331097.

Bone effect of adjuvant tamoxifen, letrozole or letrozole plus zoledronic acid in early-stage breast cancer: the randomized phase 3 HOBOE study.

BACKGROUND: To measure bone mineral density (BMD) reduction produced by letrozole as compared with tamoxifen and the benefit of the addition of zoledronic acid. PATIENTS AND METHODS: A phase 3 trial comparing tamoxifen, letrozole or letrozole+zoledronic acid in patients with hormone receptor-positive early breast cancer was conducted; triptorelin was given to premenopausal patients. Two comparisons were planned: letrozole versus tamoxifen and letrozole+zoledronic acid versus letrozole. Primary end point was the difference in 1-year change of T-score at lumbar spine (LTS) measured by dual energy X-ray absorptiometry scan. RESULTS: Out of 483 patients enrolled, 459 were available for primary analyses. Median age was 50 (range 28-80). The estimated mean difference (95% confidence interval [CI]) in 1-year change of LTS was equal to -0.30 (95% CI -0.44 to -0.17) in the letrozole versus tamoxifen comparison (P<0.0001) and to +0.60 (95% CI +0.46 to +0.77) in the letrozole+zoledronic acid versus letrozole comparison (P<0.0001). Bone damage by letrozole decreased with increasing baseline body mass index in premenopausal, but not postmenopausal, patients (interaction test P=0.004 and 0.47, respectively). CONCLUSIONS: In the HOBOE (HOrmonal BOne Effects) trial, the positive effect of zoledronic acid on BMD largely counteracts damage produced by letrozole as compared with tamoxifen. Letrozole effect is lower among overweight/obese premenopausal patients.

Is epirubicin effective in first-line chemotherapy of metastatic breast cancer (MBC) after an epirubicin-containing adjuvant treatment? A single centre phase III trial.

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-2 (D) with the combination of docetaxel 80 mg m-2 and epirubicin 75 mg m-2 (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=26) and D arms (n=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.

Multimodal treatment strategy for locally advanced breast cancer.

Between 1990 and 1995, 87 patients with locally advanced breast cancer were treated with initial chemotherapy consisting of 3-4 cycles of epirubicin and then with surgery, radiotherapy and chemotherapy. All patients with positive or unknown estrogen receptor status were administered tamoxifen. A complete response was observed in 9 patients and a partial response in 64. At a mean follow-up of 29.22 months, 25 patients had died of metastatic disease, and 48 patients are disease-free. 54% patients are alive at 5 years. Statistical analysis confirmed that neither age, menopausal status, size of the primary tumor nor histology seemed to influence the Disease Free and Overall Survival. Improved survival was observed in patients with negative lymph nodes and positive receptor status. The presence of a positive receptor status may be correlated with conserved integrity of hormone sensitivity and with a good response to the hormone therapy.

Evaluation of TAG-72 as a serum marker in ovarian and breast carcinoma.

Tumor Associated Glycoprotein 72 (TAG-72) is common to most epithelial tumors. In this study serum levels of TAG-72 were measured in 36 healthy female subjects, in 94 patients with breast cancer, and in 43 others with epithelial ovarian cancer. More particularly, 27 out of the 94 patients with breast cancer had early disease (Stage I-I; or T 0-2b; N 0-1b; M 0), while the remaining 67 had advanced disease (Stage III-IV; or T 0-4; N 0-3; M 0-1). All the 43 subjects with ovarian cancer were at stage III-IV (FIGO Classification), 12 of whom had minimal disease (lesions less than 2 cm) and the other 31 had bulky disease. 3.5 U/ml being the highest value found in the control group, we arbitrarily assumed 3.85 U/ml (mean +/- 3 SD) as the cut-off limit in this preliminary study. Among the patients with breast cancer, 17 out of the 67 subjects with advanced disease (25.3%) and 1 out of the 27 others with early disease (3.7%) exceeded the TAG-72 cut-off limit. Among the patients with ovarian cancer, 2 out of the 12 subjects with minimal disease (16.7%) and 22 out of the others 31 with bulky disease (70.9%) had TAG-72 levels above cut-off limit. High TAG-72 levels were found in all the histotypes of ovarian cancer including the mucinous type. Preliminary data seem to indicate that in ovarian cancer variations in serum levels of TAG-72 are in agreement with the trend of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)