Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer.

PURPOSE: To compare the efficacy of pegylated liposomal doxorubicin (PLD) with that of a common salvage regimen (comparator) in patients with taxane-refractory advanced breast cancer. PATIENTS AND METHODS: Following failure of a first- or second-line taxane-containing regimen for metastatic disease, 301 women were randomly assigned to receive PLD (50 mg/m(2) every 28 days); or comparator-vinorelbine (30 mg/m(2) weekly) or mitomycin C (10 mg/m(2) day 1 and every 28 days) plus vinblastine (5 mg/m(2) day 1, day 14, day 28, and day 42) every 6 to 8 weeks. Patients were stratified before random assignment based on number of previous chemotherapy regimens for metastatic disease and presence of bone metastases only. RESULTS: Progression-free survival (PFS) and overall survival (OS) were similar for PLD and comparator (PFS: hazard ratio [HR], 1.26; 95% CI, 0.98 to 1.62; P =.11; median, 2.9 months [PLD] and 2.5 months [comparator]; OS: HR, 1.05; 95% CI, 0.82 to 1.33; P =.71; median, 11.0 months [PLD] and 9.0 months [comparator]). In anthracycline-naïve patients, PFS was somewhat longer with PLD, relative to the comparator (n = 44; median PFS, 5.8 v 2.1 months; HR, 2.40; 95% CI, 1.16 to 4.95; P =.01). Most frequently reported adverse events were nausea (23% to 31%), vomiting (17% to 20%), and fatigue (9% to 20%) and were similar among treatment groups. PLD-treated patients experienced more palmar-plantar erythrodysesthesia (37%; 18% grade 3, 1 patient grade 4) and stomatitis (22%; 5% grades 3/4). Neuropathy (11%), constipation (16%), and neutropenia (14%) were more common with vinorelbine. Alopecia was low in both the PLD and vinorelbine groups (3% and 5%). CONCLUSION: PLD has efficacy comparable to that of common salvage regimens in patients with taxane-refractory metastatic breast cancer, thereby representing a useful therapeutic option.

Quimioterapia primária em câncer de mama localmente avançado: estudo comparativo entre dois esquemas terapêuticos com intensificaçäo de doses / Primary chemotherapy in locally advanced breast cancer: comparative trial of two regimens with dose intensification

Realizou-se um estudo clínico prospectivo, fase III, multicêntrico, aberto, aleatório e comparativo. Foram avaliadas 60 pacientes portadoras de câncer de mama localmente avançado, estádio IIIA, divididas em dois grupos. As pacientes foram submetidas à quimioterapia primária, com ou sem intensificaçäo de dose, por quatro ciclos, e à cirurgia. Utilizou-se o protocolo FEC 50 no Grupo A (5-FU 500 mg/m², epirubicina 50 mg/m² e ciclofosfamida 500 mg/m²) e o FEC 100 no Grupo B (5-FU 500 mg/m², epirubicina 100 mg/m² e ciclofosfamida 500 mg/m²). Foram analisados, durante a quimioterapia, o estado geral, variaçÝo ponderal, alopécia, alteraçöes digestivas, hematológicas e cardiotoxicidade. Após a quimioterapia avaliou-se a resposta tumoral clínica e, na peça cirúrgica, a resposta anatomopatológica. A resposta clínica objetiva (resposta completa e resposta parcial) nos grupos A e B foi 93 porcento e 96 porcento, respectivamente. Os resultados foram similares, porém no Grupo B houve um percentual maior de respostas clínicas completas. Avaliou-se a doença residual no sítio primário e nos linfonodos axilares. No Grupo A houve 4 (13 porcento) casos de resposta anatomopatológica completa, 12 (40 porcento) de tumor residual microscópico e 14 (47 porcento) de tumor macroscópico. No Grupo B ocorreram 10 (33 porcento) casos de resposta anatomopatológica completa, 7 (23 porcento) de tumor residual microscópico e 13 (44 porcento) de tumor macroscópico. Concluiu-se que a quimioterapia primária proporcionou resposta clínica e anatomopatológica maior no grupo com intensificaçäo de dose. A toxicidade, tolerável e reversível, foi mais acentuada no grupo de altas doses.