Efficacy and safety findings from DREAM: a phase III study of DHP107 (oral paclitaxel) versus i.v. paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy.

Background: Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure. Methods and materials: Patients were randomized 1 : 1 to DHP107 (200 mg/m2 orally twice daily days 1, 8, 15 every 4 weeks) or i.v. paclitaxel (175 mg/m2 day 1 every 3 weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6 weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25. Results: Baseline characteristics were balanced in the 236 randomized patients (n = 118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7-4.0) months for DHP107 and 2.6 (95% CI 1.8-2.8) months for paclitaxel (hazard ratio [HR] = 0.85; 95% CI 0.64-1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR = 0.93; 95% CI 0.70-1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1 - 11.5) months for DHP107 versus 8.9 (95% CI 7.1-12.2) months for paclitaxel (HR = 1.04; 95% CI 0.76-1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%). Conclusions: DHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC. ClinicalTrials.gov: NCT01839773.

Correlation of temporal lobe glucose metabolism with the Wada memory test.

PURPOSE: The goal of the present study was to examine the relationship of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and the Wada memory test in lateralizing memory dominance and epileptic focus. METHODS: FDG-PET and the Wada test were performed in 18 patients with temporal lobe epilepsy (TLE). The asymmetry indices of FDG-PET (PET-AI) were calculated in mesial, polar, anterolateral, midlateral, and posterolateral regions of the temporal lobe, and those of Wada memory test (Wada-AI) were obtained as well. RESULTS: The Wada-AI was significantly correlated with PET-AI in mesial (r = 0.67, p = 0.003), polar (r = 0.55, p = 0.019), anterolateral (r = 0.55, p = 0.019), and midlateral (r = 0.51, p = 0.031) regions of the temporal lobe. However, after a linear regression analysis, PET-AI of only the mesial temporal region was significantly correlated with Wada-AI (p = 0.008). Wada-AI could correctly lateralize the seizure focus in 90% of the left TLE and 75% of the right TLE patients. The PET-AI of the mesial temporal region showed the highest sensitivity of seizure lateralization (80% of left TLE and 87.5% of right TLE). PET-AI of other temporal regions had lower sensitivities (50-80% of left TLE, 20-75% of right TLE). One or two patients showed false seizure lateralization by PET-AI on each temporal region. CONCLUSIONS: Although FDG-PET hypometabolism is observed at both mesial and lateral regions of the temporal lobe in mesial TLE, mesial temporal region appeared to be a dominant and leading area for lateralizing Wada memory dominance and epileptic focus.