The primary objective was achieved, with vandetanib 100 mg plus docetaxel demonstrating a significant prolongation of PFS compared with docetaxel in relation to the prespecified significance level. On the basis of these encouraging data, phase III evaluation of vandetanib 100 mg plus docetaxel in second-line NSCLC has been initiated.

Background: Clinically significant benign stenoses of the large airways develop in about 1% of patients after intubation. The management of benign stenoses is not unified around the world, nor are there any accepted methods for their screening. Objectives: The purpose of this study is to describe and compare results of interventional bronchoscopy and surgical therapy of benign stenoses as well as to propose an algorithm for the management of this airways disorder. Methods: Prospective study on 80 consecutive patients with benign stenoses of the large airways admitted to the Pulmonary Department of the University Hospital of Prague-Motol. Results: Sixty-two patients developed stenoses after endotracheal intubation or tracheostomy, in 18 patients the stenosis was caused by other diseases or pathological situations. Thirty-eight patients were sent for surgical resection of the stenotic part of the airways. 2 surgically treated patients developed recurrence of the stenosis and had to be reoperated on. Narrowing of the trachea at the site of end-to-end anastomosis developed in 6 other patients and was cured by interventional bronchoscopy. The remaining 42 patients were treated by interventional bronchoscopy (Nd-YAG laser, electrocautery, stent) which was curative in 35 patients. Sixty-five patients were alive at the time of evaluation, 15 patients died. Five of them died between 3 and 14 (median 4) months after surgery from a disease other than airway stenosis. Ten nonresected patients also died, with 1 exception, due to a disease other than airway stenosis; the median survival was 9 months. Conclusions: We recommend to assess the patient for surgery after the initial diagnosis and therapeutic bronchoscopy with dilatation of the stenosis. If the patient is not a suitable candidate for resection, interventional bronchoscopy is an appropriate alternative for the management of benign stenoses of the large airways.

7016 Background: ZD6474, a once-daily oral agent, targets key signaling pathways in cancer by inhibiting VEGF, EGF and RET receptor tyrosine kinases. ZD6474 in combination with docetaxel (Doc) was assessed in patients (pts) with refractory non-small-cell lung cancer (NSCLC). Methods: Pts eligible for this randomized, double-blind study had locally advanced or metastatic (stage IIIB/IV) NSCLC after failure of 1st-line platinum-based chemotherapy. The primary objective was to determine whether once-daily oral ZD6474 (100 or 300 mg) + Doc (75 mg/m2 i.v. infusion every 21 days) prolonged progression-free survival (PFS) vs Doc alone (80% power to detect 50% prolongation at P<0.2). Overall survival was a secondary objective. Results: A total of 127 pts (73 male/54 female; median age 59 yrs, range 29–82) received ZD6474 100 mg + Doc (n=42), ZD6474 300 mg + Doc (n=44) or Doc (n=41). The study met its primary objective of PFS prolongation with the addition of ZD6474: median PFS was 19 wks for ZD6474 100 mg + Doc (HR=0.64; P=0.074); 17 wks for ZD6474 300 mg + Doc (HR=0.83; P=0.461); and 12 wks for Doc. A total of 64 pts (50%) presented with histology other than adenocarcinoma, including 37 with squamous, and 13 pts (10%) entered with CNS metastases. Exploratory subgroup analyses suggest advantages in PFS for ZD6474 + Doc vs Doc both for adenocarcinoma and for other lung cancer histologies. Common adverse events (AEs) included diarrhea, rash and asymptomatic QTc prolongation, all responded to standard management or dose interruption/reduction. Four pts with squamous experienced hemoptysis (ZD6474 100 mg + Doc, n=2 CTC grade 1/2; Doc, n=2 CTC grade 3/4). No fatal episodes of hemoptysis or any CNS hemorrhage AEs were reported in pts receiving ZD6474. Overall survival data were immature at the time of PFS analysis, and a mature survival analysis will be conducted at ∼75% of deaths (anticipated April 2006, and will be presented at the meeting). As of December 2005, 40/127 (31%) pts were alive, 5 of whom continue to receive ZD6474. The minimum follow-up of pts still alive was 17 months. Conclusions: ZD6474 + Doc prolonged PFS vs Doc alone, and these promising data have led to the initiation of Phase III evaluation of ZD6474 + Doc in 2nd-line NSCLC. [Table: see text]