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Purpose: To evaluate the efficacy of the aromatase inhibitor letrozole in preselected estrogen receptor (ER)–positive relapsed epithelial ovarian cancer patients and to identify markers that predict endocrine-sensitive disease. Experimental Design: This was a phase II study of letrozole 2.5 mg daily until clinical or marker evidence of disease progression in previously treated ER-positive ovarian cancer patients with a rising CA125 that had progressed according to Rustin's criteria. The primary end point was response according to CA125 and response evaluation criteria in solid tumors (RECIST) criteria. Marker expression was measured by semiquantitative immunohistochemistry in sections from the primary tumor. Results: Of 42 patients evaluable for CA125 response, 7 (17%) had a response (decrease of >50%), and 11 (26%) patients had not progressed (doubling of CA125) following 6 months on treatment. The median time taken to achieve the CA125 nadir was 13 weeks (range 10-36). Of 33 patients evaluable for radiological response, 3 (9%) had a partial remission, and 14 (42%) had stable disease at 12 weeks. Eleven patients (26%) had a PFS of >6 months. Subgroup analysis according to ER revealed CA125 response rates of 0% (immunoscore, 150-199), 12% (200-249), and 33% (250-300); P = 0.028, χ2 for trend. Expression levels of HER2, insulin-like growth factor binding protein 5, trefoil factor 1, and vimentin were associated with CA125 changes on treatment. Conclusions: This is the first study of a hormonal agent in a preselected group of ER-positive ovarian cancer patients. A signature of predictive markers, including low HER2 expression, predicts response.

The pathogenesis of brain metastasis as a relatively rare complication of epithelial ovarian cancer is poorly understood. Some observations suggest that brain metastases from ovarian cancer are becoming more common and that ovarian cancers, which metastasize to the brain, may have a different biological pattern.Data were extracted from the Edinburgh Ovarian Cancer Database on a cohort of patients managed at the Edinburgh Cancer Centre (UK) between 1998 and 2004. The incidence of brain metastases was compared between patients with previous treatment for early breast cancer and patients without previous treatment for early breast cancer. Baseline characteristics, the time to cancer antigen 125 relapse, the time to brain metastasis, and the radiological pattern of relapse were also compared between these patients.We demonstrate a higher incidence of serous histology (P = 0.02) in patients in remission from early breast cancer and that the incidence of brain metastases in this group is 11.6% compared with 1.1% in patients without prior breast cancer (relative risk = 10.5, P0.001). Brain metastases were clinically evident after 45.6 months in patients with previous breast cancer compared with 21 months in patients without previous breast cancer (P = 0.008). Among the patients who developed brain metastases, isolated retroperitoneal lymph node recurrence was noticed in patients in remission from early breast cancer but rarely in other patients.Ovarian cancer patients with a history of early breast cancer have a higher incidence of brain metastases and a different pattern of disease recurrence. We speculate that a higher incidence of breast cancer early onset mutations in patients with previous early breast cancer underlies these observed differences.

46 eligible patients with either anaplastic astrocytoma (AA) or glioblastoma (GBM) and clinical and computed-tomography-confirmed relapse following primary surgery and radiotherapy received oral tauromustine 130 mg/m2 every 5 weeks. A prospective design allowed for concurrent assessment of both clinical and radiological responses and drug toxicity. 41% of patients improved clinically whilst 46% improved radiologically with 3 complete, 7 partial and 7 minimal responses (WHO criteria). Toxicity included grade III or IV gastrointestinal side-effects (15%), grade III or IV leukopenia (24%) and grade III and IV thrombocytopenia (44%). In 9 clinically responding patients, haematological toxicity led to discontinuation of treatment. All patients were followed-up until death and second-line chemotherapy was not used. Median post-treatment survival was 26 weeks for patients with GBM and 57 weeks for patients with AA. Overall 2-year survival rate was 69% for AA and 23% for GBM. Tauromustine given at the time of relapse has demonstrable antitumour activity in patients not previously treated with chemotherapy.