Broadly and finely tunable hybrid silicon laser with nanosecond-scale switching speed.

We demonstrate a hybrid silicon tunable laser with wide tunability and rapid switching speed for applications in sensing and optical networks. By implementing an optimized carrier injection phase shifter design, the filters of the silicon laser cavity may be efficiently controlled, enabling both fine and broad wavelength tuning across a 56 nm range, in addition to a rapid 10 ns switching time. The laser emits up to 10 dBm output power, and the linewidth is near 200 kHz. The fast wavelength switching demonstrated here may be employed in data center and access networks, while the potential for rapid wavelength sweeping is attractive for optical sensing and imaging applications.

A phase I trial to determine the safety, pharmacokinetics, and pharmacodynamics of intercalated BMS-690514 with paclitaxel/carboplatin (PC) in advanced or metastatic solid malignancies.

PURPOSE: A phase I dose escalation study was performed to determine the maximum tolerated dose (MTD) of intercalated dosing of BMS-690514, a reversible oral panHER/VEGF receptor inhibitor, combined with paclitaxel/carboplatin (PC) in advanced solid tumors. Secondary endpoints included safety, pharmacokinetics (PK), exploratory pharmacodynamics (PD), and preliminary efficacy. EXPERIMENTAL DESIGN: Patients received fixed doses of P (200 mg/m(2)) and C (AUC 6 mg/mL min) q21 days with intercalated BMS-690514 (Days 4-19) starting at 100 mg/day and increasing by 50 mg/day using a 3 + 3 dose escalation design until the MTD was reached. Twenty additional patients were enrolled in the expansion cohort at the recommended phase II dose (RP2D). RESULTS: The MTD was reached at 150 mg/day. DLTs included grade 3 thrombosis at 100 mg (1 patient) and grade 3 diarrhea at 150 mg (1 patient) and 200 mg (2 patients). Serious adverse events (AEs) occurring in 20/37 patients included neutropenia (n = 5), diarrhea (n = 4), pulmonary embolism (n = 3), and simultaneous dehydration, acute renal failure, and febrile neutropenia (n = 2). BMS-690514-related AEs included diarrhea (97 %), acneiform rash (60 %), fatigue (43 %), nausea (30 %), and anorexia (30 %). There were no treatment-related deaths. Sequential intermittent administration of PC did not affect the PK of BMS-690514. Of the 32 patients evaluable for efficacy, there were 12 partial responses including five patients with non-small-cell lung cancer and 12 patients with stable disease. CONCLUSIONS: The MTD of intercalated BMS-609514 combined with PC was 150 mg/day. This approach was tolerable with manageable toxicities and antitumor activity in a variety of solid tumor types.