Background: The steroidal aromatase inactivator exemestane has demonstrated activity after prior failure of non-steroidal aromatase inhibitors (including third-generation inhibitors letrozole and anastrozole) in postmenopausal women with advanced breast cancer. If exemestane is used as first anti-aromatase agent, however, it is unclear whether patients can still benefit from letrozole or anastrozole after progression. Patients and Methods: Postmenopausal patients with advanced, hormone receptor-positive or -unknown breast cancer were eligible for this study. Patients with no prior exposure to anti-aromatase drugs received exemestane, 25 mg daily, as first anti-aromatase agent. At the time of progression, patients were crossed-over to anastrozole or letrozole if further endocrine therapy was considered appropriate. Patients with prior exposure to anti-aromatase agents were also included in the study, and were given anastrozole or letrozole if they had previously received exemestane, or exemestane if they had previously received anastrozole or letrozole. The primary endpoint of the study was the clinical benefit rate (complete response + partial response + stabilization of disease for ≧24 weeks). Results: Forty patients received exemestane 25 mg daily as first anti-aromatase agent, with a CB rate of 67.5% (95% CI 52.9–82.0%) and a median time to progression (TTP) of 9.6 months. In 18 patients, letrozole (n = 17) or anastrozole (n = 1) were used after failure of exemestane: the CB rate was 55.6% (95% CI 32.6–78.5%) with a median TTP of 9.3 months. In 23 patients, exemestane was used after failure of letrozole or anastrozole: the CB rate was 43.5% (95% CI 23.2–63.7%) with a median TTP of 5.1 months. Conclusions: Our study confirms that exemestane is active after prior failure of letrozole or anastrozole. We have also shown that patients can receive exemestane as their first anti-aromatase agent and still benefit from letrozole or anastrozole after progression. This suggests that the partial non-cross resistance between steroidal and non-steroidal anti-aromatase agents is independent of the sequence employed.

The aim of this study was to identify a chemotherapy combination that would be active and well tolerated for palliative treatment of advanced non-small-cell lung cancer (NSCLC). From February 1992 to December 1994, a total of 77 patients affected by stage-IIIB and stage-IV NSCLC were treated with carboplatin 350 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8 of each cycle, with cycles repeated every 28 days. All patients were evaluable for response and toxicity. A total of 24 patients showed a partial response (31% response rate; 95% CI = 21-41%). The median duration of overall survival was 41 weeks (95% CI = 31-51), and the median time to disease progression was 34 weeks (95% CI = 25-43). The treatment was well tolerated: no grade-4 toxicity was observed. The carboplatin-vinorelbine combination deserves to considered as a valid alternative to regimens that include cisplatin for palliative treatment of advanced NSCLC.