Cediranib in combination with fulvestrant in hormone-sensitive metastatic breast cancer: a randomized Phase II study.

Hormone receptor-positive breast cancer is treated with estrogen inhibitors. Fulvestrant (FASLODEX™), an estrogen receptor (ER) antagonist with no known agonist effects, competitively binds, blocks and degrades the ER. Vascular endothelial growth factor (VEGF) may mediate resistance to ER antagonists. Cediranib is a highly potent VEGF signaling inhibitor with activity against all three VEGF receptors. This randomized Phase II study evaluated cediranib plus fulvestrant. Postmenopausal women with hormone-sensitive metastatic breast cancer were eligible. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), duration of response, clinical benefit rate (CBR), safety/tolerability and pharmacokinetics (PK). Patients received cediranib 45 mg/day (n=31) or placebo (n=31) both plus fulvestrant. Demographic/baseline characteristics were well balanced. Patients treated with cediranib had a numerical advantage in PFS (hazard ratio=0.867, P=0.669; median 223 vs. 112 days, respectively) and ORR (22 vs. 8 %, respectively) vs. placebo, although not statistically significant. CBR was 42 % in both arms. The most common adverse events (AEs) in the cediranib arm were diarrhea (68 %), fatigue (61 %) and hypertension (55 %). The incidence of grade ≥ 3 AEs (68 % vs. 32 %), serious AEs (48 % vs. 13 %), discontinuation AEs (39 % vs. 10 %), and cediranib dose reductions/interruptions (74 % vs. 32 %) were higher in the cediranib arm. There was no evidence of a clinically relevant effect of cediranib on fulvestrant PK. Cediranib plus fulvestrant may demonstrate clinical activity in this population, but cediranib 45 mg was not sufficiently well tolerated. Investigation of lower doses of cediranib plus hormonal/chemotherapy could be considered.

Ossifying fibroma: a rare cause of orbital inflammation.

PURPOSE: To describe the clinical and radiologic features of 4 cases of ossifying fibroma affecting the orbit and to review the literature on orbital involvement by the tumor. METHODS: Small case series. RESULTS: Four patients (3 children and 1 adult) with ossifying fibromas invading the orbit were examined. Two of the 3 children were examined for ossifying fibromas on the orbital roof. One had the psammomatoid form of the disease and the other the trabecular variant. Despite striking differences in the histologic pattern and in the radiologic appearance of the lesions, both children displayed a significant degree of orbital inflammation mimicking orbital cellulitis. The third child and the adult patient had the orbit involved by trabecular ossifying fibromas invading the orbital floor. The tumor of the adult clearly originated in the maxilla, filled the maxillary sinus, and eroded the orbital floor. The tumor of the third child occupied the maxillary, ethmoid, and sphenoid sinuses. In both cases, the clinical presentation was painless eye dystopia and proptosis. CONCLUSIONS: Regardless of the histologic pattern (trabecular or psammomatoid), ossifying fibromas can induce a substantial degree of orbital inflammation in children and must be included in the differential diagnosis of acute orbital inflammation during childhood.