The Political Economy of Policy Reform in the Philippines: 1992-1998

From 1992 to 1998, the Philippines saw a period of sweeping policy reforms when 273 economic, social and political legislations were adopted. When and why do policy reforms happen and what explains the scope, pace and sequencing of their implementation? My analytic narrative differs from the literature in its emphasis on: (1) the attributes of the players, particularly the role of leadership; (2) the attributes of the policy; and (3) the political rules of the game, including electoral cycles, tenure limits, veto rules and “turncoatism.”Political economy, macroeconomic policy reform, Philippines,

Phase I ficlatuzumab monotherapy or with erlotinib for refractory advanced solid tumours and multiple myeloma

BACKGROUND: Ficlatuzumab, a humanised hepatocyte growth factor (HGF) IgG1κ inhibitory monoclonal antibody, was evaluated for recommended phase II dose (RP2D), safety, pharmacokinetics (PKs), antidrug antibody (ADA), pharmacodynamics (PDs) and antitumour activity as monotherapy or combined with erlotinib. METHODS: Patients with solid tumours received ficlatuzumab 2, 5, 10 or 20 mg kg(–1) intravenously every 2 weeks (q2w). Additional patients were treated at the RP2D erlotinib. RESULTS: Forty-one patients enrolled at doses ⩽20 mg kg(–1). Common adverse events (AEs) included peripheral oedema, fatigue and nausea. Three patients experienced grade ⩾3 treatment-related hyperkalaemia/hypokalaemia, diarrhoea or fatigue. Best overall response (44%) was stable disease (SD); median duration was 5.5 months (0.4–18.7 months). One patient has been on therapy with SD for >4 years. Pharmacokinetics of ficlatuzumab showed low clearance (0.17–0.26 ml h(–1) kg(–1)), a half-life of 6.8–9.4 days and dose-proportional exposure. Ficlatuzumab/erlotinib had no impact on the PK of either agent. No ADAs were detected. Ficlatuzumab increased serum HGF levels. CONCLUSIONS: Recommended phase II dose is 20 mg kg(–1) q2w for ficlatuzumab monotherapy or with erlotinib. Preliminary antitumour activity and manageable AEs were observed. Pharmacokinetics were dose-proportional and consistent with other IgG therapeutics. Ficlatuzumab was not immunogenic, and serum HGF was a potential PD marker