Secondary outcomes included the efficacy of the treatment regimen [objective response rate, disease control rate, progression-free survival (PFS), overall survival, duration of response] and the safety of combination therapy. An exploratory objective evaluated the association between tumor EGFR and COX-2 immuno-expression and tumor response. The trial was conducted in accordance with Good Clinical Practice and the ethical principles outlined in the revised Declaration of Helsinki. Local ethics committee approval was obtained before study initiation and all participants
gave written, informed consent. Eligible patients were administered gefitinib and celecoxib, both given orally, from day 1 Inhibitors,research,lifescience,medical until disease progression, unacceptable toxicity, or withdrawal. Wherever possible, patients were followed up for ≥6 months after the start of trial therapy, with assessment on day
15 and then every 28 days thereafter. Safety and tolerability measures The nature, Inhibitors,research,lifescience,medical incidence, and severity of adverse events (AEs) were recorded throughout the study. Routine hematology, biochemistry, and physical examinations were carried out during the seven days before study entry and during the treatment phase on day 1, day 15, and every 28 days thereafter. Urinalysis Inhibitors,research,lifescience,medical was performed as necessary. Both AEs and laboratory parameters were assessed using National Cancer Romidepsin side effects Institute CTC version 2.0. Causality was assigned by the investigators. In cases where toxicity was unacceptable, dose
interruptions (≤14 days) were used as the first approach to manage toxicity. Repeat dose interruptions were permitted but if toxicity recurred on re-challenge and further Inhibitors,research,lifescience,medical interruptions were not considered to be sufficient to resolve toxicity, patients were either withdrawn from the study (for gefitinib-related toxicities) or underwent a dose reduction (for celecoxib-related toxicities). A single celecoxib dose reduction (from 400 to 200 mg bid) was permitted in patients experiencing recurring toxicity (> grade 2) to celecoxib. However, if serious GI toxicity was observed, celecoxib Inhibitors,research,lifescience,medical was discontinued and patients could continue on gefitinib monotherapy. Efficacy measures Objective tumor response (complete or partial response) was evaluated using RECIST www.selleckchem.com/products/Erlotinib-Hydrochloride.html within the 3 weeks prior to study entry, 6 weeks after the start of therapy, and every 12 weeks thereafter until disease progression. Patients were considered to have controlled disease if the RECIST criteria Entinostat for complete response, partial response, or stable disease were at any time satisfied at or before trial closure. The duration of response was defined as the number of days from the first documented response until death/progression or the last on-study tumor assessment. Likewise, time to progression (TTP) was defined as the number of days from start of treatment on day 1 until disease progression/death or the last tumor assessment.