"Docetaxel in adjuvant therapy of breast cancer: results of the TAXIT 216 multicenter trial"

The dissertation is focused on the evaluation of a Docetaxel-based sequential regimen as adjuvant therapy of breast cancer. Docetaxel is among the most active chemotherapeutic agents for breast cancer. With Taxit 216 trial, we aimed to assess the efficacy of adding docetaxel in a block-sequential fashion to a regimen with doxorubicin followed by CMF in the adjuvant therapy for node-positive early stage breast cancer (ESBC). Patients were randomized to arm A (epirubicin 120 mg/m2 for 4 cycles then cyclophosphamide, methotrexate and 5-fluorouracil [CMF] for 4 cycles), or arm B (4 cycles of docetaxel 100 mg/m2 administered after the fourth epirubicin cycle and before the first CMF cycle). Treatment allocation was performed, in our Institution, by a computer program using a minimization algorithm. Stratification factors were: center, lymph node involvement (1 to 3, 4 to 9, >10), estrogen receptor status (negative/positive/unknown), menopausal status (pre/post). The primary end-point was invasive disease-free survival (IDFS). Secondary end-points were recurrence-free survival (RFS), overall survival (OS) and toxicity. The study was designed to detect a hazard ratio of 0.70, assuming an a of 0.05 (two-sided), a power of 0.80 and an expected DFS in arm A of 0.65 at 5 years. This required 480 patients per arm and 250 events. Final results are reported according to the standardized system for efficacy end points (STEEP system). Between July 1998 and July 2002, 972 patients were randomized (486 in each arm). At a median follow-up of 62 months, 278 IDFS events were recorded. Five-year IDFS was 74% in arm B vs 68% in arm A (P = 0.13), with a hazard ratio (HR) of 0.82 (95% confidence interval [CI] = 0.64†"1.03). RFS was significantly better for arm B than for arm A (76% vs 69%; P = 0.0332) with a HR of 0.75 (95% CI = 0.59†"0.96). There was a significant improvement in OS, with an estimated five-year OS of 90% in arm B and 85% in arm A (P = 0.0168; HR = 0.67, 95% CI = 0.48†"0.94). This benefit comes at the cost of increased but acceptable toxicity. We demonstrated, with the results of the Taxit 216 phase III trial, that incorporating docetaxel into a block-sequential epirubicin†"CMF regimen significantly reduces the risk of recurrence and death in patients with nodepositive ESBC.