Docetaxel combined with trastuzumab is an active regimen in HER-2 3+ overexpressing and fluorescent in situ hybridization-positive metastatic breast cancer: a multi-institutional phase II trial.

PURPOSE: To determine the efficacy and safety of weekly docetaxel and trastuzumab as first- or second-line therapy in women with HER-2-overexpressing metastatic breast cancer and to correlate the efficacy of trastuzumab with HER-2 status as determined by immunohistochemistry assay and fluorescent in situ hybridization (FISH). PATIENTS AND METHODS: Twenty-six women with HER-2-positive (HercepTest [Dako Corp, Carpenteria, CA]2 to 3+) metastatic breast cancer were enrolled onto this study of trastuzumab (4 mg/kg load; 2 mg/kg/wk administered intravenously) and docetaxel (35 mg/m2/wk for 6 weeks). RESULTS: Using an intent-to-treat analysis, the overall response rate was 50% (13 of 26 patients). Eight patients (31%) had a period of stable disease posttherapy. Among HER-2 3+ patients, the overall response rate was 63% (12 of 19 patients) compared with a 14% response rate (one of seven patients) for HER-2 2+ patients (P=.07). Patients with FISH-positive tumors experienced an overall response rate of 64%. Median time to progression was 12.4 months for the entire cohort (HER-2 3+ tumors, 12.3 months; HER-2 2+ lesions, 9.5 months) and median survival was 22.1 months. All HER-2 3+ patients were FISH-positive; the only HER-2 2+ patient responding to treatment was also FISH-positive. Grade 4 toxicities occurred in four patients; most toxicities were mild. CONCLUSION: Trastuzumab plus docetaxel is an active and well-tolerated regimen in women with HER-2 3+ overexpressing or FISH-positive metastatic breast cancer.

Increased cochlear fluid-attenuated inversion recovery signal in patients with vestibular schwannoma.

BACKGROUND AND PURPOSE: Elevated protein levels have been reported in perilymph of patients with vestibular schwannoma. Fluid-attenuated inversion recovery (FLAIR) imaging is sensitive to high protein contents in fluids. The purpose of this study was to investigate if in patients with unilateral vestibular schwannoma, cochlear FLAIR signal intensity on the affected side is increased compared with the unaffected side and control subjects. MATERIALS AND METHODS: Fifteen patients with unilateral vestibular schwannoma and 25 age-matched control subjects (without a history of hearing loss) were retrospectively evaluated. All patients and controls had routine 5-mm FLAIR and T1- and T2-weighted imaging of the brain. The signal intensity of both cochleae was evaluated by placing a small region of interest on FLAIR images. The signal intensity of the brain stem was also determined by placing a second region of interest. A ratio of cochlear signal intensity to brain stem signal intensity (CIBI ratio) was determined. A t test was used to compare the CIBI ratios. RESULTS: In patients, the mean CIBI ratio of the affected side was 0.89 +/- 0.18, and that of the unaffected side was 0.57 +/- 0.12. In control subjects, it was 0.51 +/- 0.07. The CIBI ratio of the affected side was significantly higher compared with the unaffected side (P < .001) and compared with control subjects (P < .001). CONCLUSION: Patients with vestibular schwannoma have increased cochlear FLAIR signal intensity on the affected side compared with the unaffected side and healthy subjects.