FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: the randomized phase III EAGLE study.

BACKGROUND: A targeted agent combined with chemotherapy is the standard treatment in patients with metastatic colorectal cancer (mCRC). The present phase III study was conducted to compare two doses of bevacizumab combined with irinotecan, 5-fluorouracil/leucovorin (FOLFIRI) in the second-line setting after first-line therapy with bevacizumab plus oxaliplatin-based therapy. PATIENTS AND METHODS: Patients were randomly assigned to receive FOLFIRI plus bevacizumab 5 or 10 mg/kg in 2-week cycles until disease progression. The primary end point was progression-free survival (PFS), and secondary end points included overall survival (OS), time to treatment failure (TTF), and safety. RESULTS: Three hundred and eighty-seven patients were randomized between September 2009 and January 2012 from 100 institutions in Japan. Baseline patient characteristics were well balanced between the two groups. Efficacy was evaluated in 369 patients (5 mg/kg, n = 181 and 10 mg/kg, n = 188). Safety was evaluated in 365 patients (5 mg/kg, n = 180 and 10 mg/kg, n = 185). The median PFS was 6.1 versus 6.4 months (hazard ratio, 0.95; 95% confidence interval [CI] 0.75-1.21; P = 0.676), and median TTF was 5.2 versus 5.2 months (hazard ratio, 1.01; 95% CI 0.81-1.25; P = 0.967), respectively, for the bevacizumab 5 and 10 mg/kg groups. Follow-up of OS is currently ongoing. Adverse events, including hypertension and hemorrhage, occurred at similar rates in both groups. CONCLUSION: Bevacizumab 10 mg/kg plus FOLFIRI as the second-line treatment did not prolong PFS compared with bevacizumab 5 mg/kg plus FOLFIRI in patients with mCRC. If bevacizumab is continued after first-line therapy in mCRC, a dose of 5 mg/kg is appropriate for use as second-line treatment. CLINICAL TRIAL IDENTIFIER: UMIN000002557.

[Retinitis pigmentosa with uveal effusion syndrome, a case report].

We reported a 65 year old female patient with retinitis pigmentosa accompanied by unilateral uveal effusion syndrome. Reduction in visual acuity and loss of depth of the anterior chamber were followed by peripheral choroidal detachment and then by retinal detachment. Subretinal fluid shifted to the lower part of the fundus for a short period and easily shifted to the posterior pole in a supine position. The axial length of both eyes was 21.3 mm. Fluorescein angiography revealed no definite points of leakage or abnormally dilated vessels. Chorioretinal detachment gradually disappeared with systemic steroid therapy. After that two recurrences, both of which were accompanied with loss of depth of the anterior chamber, we found during a follow-up period of two years. We thought this combination of retinitis pigmentosa and uveal effusion syndrome to be incidental. Since the exudative fluid easily accumulated in the subretinal space and shifted according to the head position, retinochoroidal adherence in retinitis pigmentosa may not be so strong as previously presumed.

[Percutaneous cryosurgery for liver tumors].

A new cryoprobe developed in our department makes it possible to perform percutaneous cryoablation for small liver tumors. This cryoprobe is placed into each lesion using an ultrasonic guidance technique. In this study there were 10 patients with hepatocellular carcinoma and 5 patients with liver metastases from colorectal carcinoma. In 6 cases the tumor size was below 2 cm, in 6 cases between 2 and 3 cm, and in 3 cases over 3 cm. Using a cryoprobe of 3 mm in diameter, each lesion was frozen using liquid nitrogen for 15 or 20 minutes then thawed for 10 minutes, and repeated. The ice ball was found to enlarge to 3 cm in 20 minutes and 5 cm in 60 minutes experimentally. Six cases were CR, 5 PR, 2 NC and 2 PD. After cryoablation, liver function did not change and there were no complications. However, as the size of the ice ball was small (about 3 cm), this method was insufficiently effective in some cases. Percutaneous cryoablation using this probe should be performed for tumors smaller than 3 cm.