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.

Second-line chemotherapy in relapsing or refractory patients with non-small cell lung cancer.

PURPOSE: A comprehensive review of the literature on the efficacy of antitumor agents either alone or in combination as second-line chemotherapy in advanced non-small cell lung cancer (NSCLC) cancer was undertaken. RESULTS: An increasing number of patients with advanced NSCLC who progress or fail to respond to front-line chemotherapy are young and in good performance status, requiring further treatment. Since advanced NSCLC is an incurable and fatal disease, the aims of second-line chemotherapy should be the palliation of the symptoms and, probably, the improvement of survival. Docetaxel, gemcitabine, irinotecan and paclitaxel have shown a promising activity as second-line treatment in patients with NSCLC, and several phase II studies of regimens associating either these drugs or these drugs with CDDP and ifosfamide have shown objective responses ranging from 15 to 25% and a median survival ranging from 4 to 8 months. Two randomized trials have clearly demonstrated that single agent docetaxel in the second line setting confers a survival benefit and an improvement of both the quality of life and the control of tumor-related symptoms establishing, thus, the role of docetaxel as standard treatment for relapsing or refractory patients with NSCLC. CONCLUSIONS: Increasing evidence from both phase II and III studies seems to indicate that second-line chemotherapy may confer a survival benefit in a selected group of patients with advanced NSCLC.