Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer--8-year results of the Breast International Group 02-98 phase III trial.

Background In women with node-positive breast cancer, the Breast International Group (BIG) 02-98 tested the incorporation of docetaxel (Taxotere) into doxorubicin (Adriamycin)-based chemotherapy, and compared sequential and concurrent docetaxel. At 5 years, there was a trend for improved disease-free survival (DFS) with docetaxel. We present results at 8-year median follow-up and exploratory analyses within biologically defined subtypes. Methods Patients were randomly assigned to one of four treatments: (i) sequential control: doxorubicin (A) (75 mg/m(2)) × 4 →classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF); (ii) concurrent control: doxorubicin, cyclophosphamide (AC)(60/600 mg/m(2)) × 4 →CMF; (iii) sequential docetaxel: A (75 mg/m(2)) × 3 → docetaxel (T) (100 mg/m(2)) × 3 → CMF and (iv) concurrent docetaxel: AT(50/75 mg/m(2)) × 4 →CMF. The primary comparison evaluated docetaxel efficacy regardless of the schedule. Exploratory analyses were undertaken within biologically defined subtypes. Results Two thousand eight hundred and eighty-seven patients were enrolled. After 93.4 months of median follow-up, there were 916 DFS events. For the primary comparison, there was no significant improvement in DFS from docetaxel [hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.80-1.05, P = 0.187]. In secondary comparisons, sequential docetaxel significantly improved DFS compared with sequential control (HR = 0.81, 95% CI = 0.67-0.99, P = 0.036), and significantly improved DFS (HR = 0.84, 95% CI = 0.72-0.99, P = 0.035) and overall survival (OS) (HR = 0.79, 95% CI = 0.65-0.98, P = 0.028) compared with concurrent doxorubicin-docetaxel. Luminal-A disease had the best prognosis. HRs favored addition of sequential docetaxel in all subtypes, except luminal-A; but this observation was not statistically supported because of limited numbers. Conclusion With further follow-up, the sequential docetaxel schedule resulted in significantly better OS than concurrent doxorubicin-docetaxel, and continued to show better DFS than sequential doxorubicin-based control.

Exemestane as primary treatment of oestrogen receptor-positive breast cancer in postmenopausal women: a phase II trial.

To assess the efficacy of exemestane as neoadjuvant treatment, 55 postmenopausal women (mean age: 76 years; range: 66-86) with oestrogen-positive non-metastatic breast tumour and ineligible for conservative surgery were recruited into this phase II trial to receive oral exemestane (25 mg day(-1)) for 6 months. Tumour response was evaluated by clinical examination, mammography and breast ultrasound every 2 months (RECIST criteria). Overall clinical response to treatment was observed in 33/54 patients (61.1%; 95% CI: 48.1-74.0). Radiological responses in 45 evaluable patients were partial response in 23, stable disease in 21 and disease progression in one. Median time to surgery from the commencement of treatment was 7 months; conservative surgery in 24 patients (55.8%) and mastectomy in 19 patients (34.5%); no surgery (patient choice or considered not suitable by attending physician) in 12 patients. Pathologic complete response was observed in breast and axilla in one patient (2.3%) and different forms of persistent disease in 23 (53.5%) patients. Treatment tolerance was good. No patient withdrew from the study because of toxic events. We conclude that exemestane as a primary treatment is feasible and very active in elderly patients with large-sized breast cancer tumour. Conservative surgery is feasible in responding patients. No severe adverse events were detected. The optimal hormonal treatment schedule remains to be determined.

[Dose intensity received in breast cancer treatment with chemotherapy]. / Intensidad de dosis recibida en el tratamiento quimioterápico del cáncer de mama.

OBJECTIVE: To know relative dose intensity (RDI) in patients with breast cancer treated with chemotherapy. To determine the number of patients where RDI was < 85% of that programmed and the possible cause. METHOD: Retrospective study, four-month selection period. The following were recorded: age, body surface, protocol applied, intention of treatment, frequency of administration of cycles, number of cytostatic treatments previously received and filgrastim administration. The average RDI per patient and protocol was calculated. RESULTS: 110 patients were analysed, the average age of them being 55.4 years (interval: 31-84), average body surface 1.7 m2 (1.3-2.4). Overall average RDI was 91.0% (SD 10.7). 93.8% (10.6), 95.8% (6.3) and 81.9% (18.5) in neoadjuvant, adjuvant and palliative treatments, respectively. 20% of the patients did not reach a RDI = 85% of that programmed, average RDI 69.5% (3.29). A delay in the administration of chemotherapy equal or greater than seven days occurred in 45.4% of the cases, average RDI 80.7% (16.0). In the episodes where the dose was reduced because of toxicity, the RDI was 75.6% (13.6). Significant inverse ratios were obtained with age (p = 0.02) and line of treatment (p = 0.03) with the RDI. In 36.8%, dose reduction was caused by neutropenia; 52.9% received filgrastim. CONCLUSIONS: Most patients received the appropriate RDI. Age, previous treatments and intention of treatment were the variables with the greatest impact on the dose received. The delay in administering the cycle was the most frequent act minimising the toxicity and which least affected the treatment.