Planning and scheduling for petroleum refineries using mathematical programming

The objective of this paper is the development and solution of nonlinear and mixed-integer (MIP) optimization models for real-world planning and scheduling problems in petroleum refineries. Firstly, we present a nonlinear planning model that represents a general refinery topology and allows implementation of nonlinear process models as well as blending relations. The optimization model is able to define new operating points, thus increasing the production of the more valuable products and simultaneously satisfying all specification constraints. The second part addresses scheduling problems in oil refineries, which are formulated as MIP optimization models and rely on both continuous and discrete time representations. Three practical applications closely related to the current refinery scenario are presented. The first one addresses the problem of crude oil inventory management of a refinery that receives several types of crude oil delivered exclusively by a single oil pipeline. Subsequently, two optimization models intended to define the optimal production policy, inventory control and distribution are proposed and solved for the fuel oil and asphalt plant. Finally, the planning model of Moro et al. (1998) is extended in order to sequence decisions at the scheduling level in the liquefied petroleum gas (LPG) area for maximization of the production of petrochemical-grade propane and product delivery

A randomized, phase 2 study of cetuximab plus cisplatin with or without paclitaxel for the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck

B490 (EudraCT# 2011-002564-24) is a randomized, phase 2b, noninferiority study investigating the efficacy and safety of first-line cetuximab plus cisplatin with/without paclitaxel (CetCis versus CetCisPac) in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Eligible patients had confirmed R/M SCCHN (oral cavity/oropharynx/larynx/hypopharynx/paranasal sinus) and no prior therapy for R/M disease. Cetuximab was administered on day 1 (2-h infusion, 400 mg/m(2)), then weekly (1-h infusions, 250 mg/m(2)). Cisplatin was given as a 1-h infusion (CetCis arm: 100 mg/m(2); CetCisPac arm: 75 mg/m(2)) on day 1 of each cycle for a maximum of six cycles. Paclitaxel was administered as a 3-h infusion (175 mg/m(2)) on day 1 of each cycle. After six cycles, maintenance cetuximab was administered until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). We assumed a noninferiority margin of 1.40 as compatible with efficacy. A total of 201 patients were randomized 1 : 1 to each regimen; 191 were assessable. PFS with CetCis (median, 6 months) was noninferior to PFS with CetCisPac (median, 7 months) [HR for CetCis versus CetCisPac 0.99; 95% CI: 0.72-1.36, P = 0.906; margin of noninferiority (90% CI of 1.4) not reached]. Median overall survival was 13 versus 11 months (HR = 0.77; 95% CI: 0.53-1.11, P = 0.117). The overall response rates were 41.8% versus 51.7%, respectively (OR = 0.69; 95% CI: 0.38-1.20, P = 0.181). Grade a parts per thousand3 adverse event rates were 76% and 73% for CetCis versus CetCisPac, respectively, while grade 4 toxicities were lower in the two-drug versus three-drug arm (14% versus 33%, P = 0.015). No toxic death or sepsis were reported and cardiac events were negligible (1%). The two-drug CetCis regimen proved to be noninferior in PFS to a three-drug combination with CetCisPac. The median OS of both regimens is comparable with that observed in EXTREME, while the life-threatening toxicity rate appeared reduced