Sequential treatment with exemestane and non-steroidal aromatase inhibitors in advanced breast cancer.

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 >or=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.

[Radiotherapy of malignant gliomas: results from conventional treatment methods and the prospects of advanced techniques].

PURPOSE: The results of post-operative radiation therapy of malignant gliomas are disappointing, with mean survival time (MST) of 16-70 weeks and 2-year survival rates ranging from 8.5% to 25% in the literature. A slightly more favourable prognosis is found in the following cases: in anaplastic astrocytomas with respect to glioblastoma multiforme; in younger patients with respect to the more elderly; the longer the duration of symptoms before diagnosis; and in the event in which surgery has been macroscopically radical. An improvement in treatment outcome is foreseeable with the use of advanced volume definition techniques for radiation therapy. MATERIALS AND METHODS AND RESULTS: Our experience with conventional radiation treatment shows therapeutic results in agreement with other institutions. In the overall 134 cases MST was 50 weeks and the 2-year survival rate was 10%. In patients affected by anaplastic astrocytoma MST was 58% and 2-year survival rate was 17%, whereas the figures for glioblastoma multiforme were 47 weeks and 8% (p>0.05, not statistically significant, probably due to the small number of cases). Patients of sixty years of age or less showed a more statistically favourable prognosis: MST was 59 weeks and 2-year survival rate was 16%, compared with 44 weeks and 4% in patients above 60 years of age (p<0.05). The duration of symptoms of 6 months or less had a less favourable prognosis with respect to symptom onset of greater than 6 months: in the former MST was 49 weeks and 2-year survival was 7%, and in the latter the figures were 68 weeks and 40% (P<0.05). Lastly, the presence of residual neoplastic tissue after surgery is an unfavourable element: in this case MST was 41 weeks and 2-year survival was 7%, compared with 68 weeks and 13% (P<0.05) after macroscopically radical surgery. DISCUSSION AND CONCLUSIONS: Computed tomography (CT) is still today an indispensable technique for radiation therapy planning. Magnetic Resonance (MR) imaging, nonetheless, provides greater definition of the neoplastic extension. The possibility of combining CT and MR neuroimaging data together with stereotactic radiotherapy techniques enables the optimal development of the three-dimensional treatment plane. This translates into high dose delivery to the neoplastic volumes without affecting the regions of the brain with no tumour involvement. Furthermore, a real improvement in the prognosis of malignant gliomas must also consider the results from research in the fields of tumour biology and functional neuroimaging.