Postoperative Adjuvant Lapatinib and Concurrent Chemoradiotherapy Followed by Maintenance Lapatinib Monotherapy in High-Risk Patients With Resected Squamous Cell Carcinoma of the Head and Neck: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study.

PURPOSE: This multicenter phase III study evaluated the efficacy and safety of lapatinib, an epidermal growth factor receptor/ErbB2 inhibitor, administered concomitantly with chemoradiotherapy and as maintenance monotherapy in patients with high-risk surgically treated squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with resected stage II to IVA SCCHN, with a surgical margin ≤ 5 mm and/or extracapsular extension, were randomly assigned to chemoradiotherapy (66 Gy total radiation dose and cisplatin 100 mg/m(2) per day administered on days 1, 22, and 43) plus placebo or lapatinib (1,500 mg per day) before and during chemoradiotherapy, followed by 12 months of maintenance monotherapy. RESULTS: Six hundred eighty-eight patients were enrolled (lapatinib, n = 346; placebo, n = 342). With a median follow-up time of 35.3 months, the study ended early because of the apparent plateauing of disease-free survival (DFS) events. Median DFS assessed by an independent review committee was 53.6 months and not reached for lapatinib and placebo, respectively (hazard ratio, 1.10; 95% CI, 0.85 to 1.43). Investigator-assessed results confirmed the independent review committee assessment. No significant differences in DFS by human papillomavirus status or overall survival were observed between treatment arms. Similar numbers of patients in both treatment arms experienced adverse events (AEs), with more patients in the lapatinib arm than the placebo arm experiencing serious AEs (48% v 40%, respectively). The most commonly observed treatment-related AEs were diarrhea and rash, both predominantly in the lapatinib arm. CONCLUSION: Addition of lapatinib to chemoradiotherapy and its use as long-term maintenance therapy does not offer any efficacy benefits and had additional toxicity compared with placebo in patients with surgically treated high-risk SCCHN.

Once-Daily Fluticasone Propionate is as Effective as Twice-Daily Treatment in Stable, Mild-to-Moderate Childhood Asthma.

OBJECTIVE: To test the hypothesis that once-daily treatment with fluticasone propionate is as effective as twice-daily treatment in children with well controlled asthma. DESIGN: Multicentre, randomised, double-blind, parallel-group study. SETTING: General practice, 86 UK centres. PATIENTS: 328 children with a diagnosis of asthma and a mean age of 10 years (range 4-16 years), mean duration of asthma of 5.5 years, and a mean percentage predicted forced expiratory volume in 1 second prior to randomisation of 93% were randomised. INTERVENTIONS: Patients entered a 4-week, open run-in period, receiving fluticasone propionate 50mug twice daily via a Diskustrade mark inhalation device. Patients whose asthma was well controlled according to predefined criteria were randomised to receive either fluticasone propionate 100mug at night and placebo in the morning (once daily [od] group; n = 151) or fluticasone propionate 50mug twice daily (bd) [bd group; n = 177] for 8 weeks. MAIN OUTCOME MEASURES: Mean morning peak expiratory flow over the 8 weeks of treatment, recorded daily, adjusted for baseline, age, height and sex. RESULTS: The 90% CI for the treatment difference in morning peak flow (bd-od) in the intention-to-treat population was -1.9 to 5.3 L/min, demonstrating clinical equivalence between bd and od administration. Fifteen patients withdrew from the study due to asthma-related problems, ten patients from the od group and five from the bd groups (p = 0.10). Both groups remained well controlled in terms of lung function, symptoms and use of relief medication throughout the study. CONCLUSIONS: Once-daily treatment with fluticasone propionate 100mug at night is as effective as 50mug twice daily in children with well controlled mild-to-moderate asthma.