Neoadjuvant chemotherapy and radiotherapy followed by surgery in selected patients with stage IIIB non-small-cell lung cancer: a multicentre phase II trial.

BACKGROUND: Stage IIIB non-small-cell lung cancer (NSCLC) is usually thought to be unresectable, and is managed with chemotherapy with or without radiotherapy. However, selected patients might benefit from surgical resection after neoadjuvant chemotherapy and radiotherapy. The aim of this multicentre, phase II trial was to assess the efficacy and toxicity of a neoadjuvant chemotherapy and radiotherapy followed by surgery in patients with technically operable stage IIIB NSCLC. METHODS: Between September, 2001, and May, 2006, patients with pathologically proven and technically resectable stage IIIB NSCLC were sequentially treated with three cycles of neoadjuvant chemotherapy (cisplatin with docetaxel), immediately followed by accelerated concomitant boost radiotherapy (44 Gy in 22 fractions) and definitive surgery. The primary endpoint was event-free survival at 12 months. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00030810. FINDINGS: 46 patients were enrolled, with a median age of 60 years (range 28-70). 13 (28%) patients had N3 disease, 36 (78%) had T4 disease. All patients received chemotherapy; 35 (76%) patients received radiotherapy. The main toxicities during chemotherapy were neutropenia (25 patients [54%] at grade 3 or 4) and febrile neutropenia (nine [20%]); the main toxicity after radiotherapy was oesophagitis (ten patients [29%]; nine grade 2, one grade 3). 35 patients (76%) underwent surgery, with pneumonectomy in 17 patients. A complete (R0) resection was achieved in 27 patients. Peri-operative complications occurred in 14 patients, including two deaths (30-day mortality 5.7%). Seven patients required a second surgical intervention. Pathological mediastinal downstaging was seen in 11 of the 28 patients who had lymph-node involvement at enrolment, a complete pathological response was seen in six patients. Event-free survival at 12 months was 54% (95% CI 39-67). After a median follow-up of 58 months, the median overall survival was 29 months (95% CI 16.1-NA), with survival at 1, 3, and 5 years of 67% (95% CI 52-79), 47% (32-61), and 40% (24-55). INTERPRETATION: A treatment strategy of neoadjuvant chemotherapy and radiotherapy followed by surgery is feasible in selected patients. Toxicity is considerable, but manageable. Survival compares favourably with historical results of combined treatment for less advanced stage IIIA disease. FUNDING: Swiss Group for Clinical Cancer Research (SAKK) and an unrestricted educational grant by Sanofi-Aventis (Switzerland).

Effects of probucol versus aspirin and versus brachytherapy on restenosis after femoropopliteal angioplasty: the PAB randomized multicenter trial.

PURPOSE: To evaluate the effect of probucol and/or of endovascular brachytherapy (EVBT) on restenosis after percutaneous transluminal angioplasty (PTA) of femoropopliteal arteries. METHODS: A total of 335 patients (206 men; mean age 72+/-9 years) with intermittent claudication were randomized according to a 2x2 factorial design to 1 of the 4 groups: probucol, placebo, EVBT, and EVBT+probucol. Probucol (1 g/d) or placebo were given in double-blinded fashion 1 month before and for 6 months after PTA. Gamma irradiation (192Iridium, 14 Gy, 5-mm reference depth) was randomly applied in an unblinded manner from a noncentered endoluminal catheter. All patients received aspirin (100 mg/d). Primary endpoint was restenosis (>50% diameter reduction) detected by duplex ultrasound 6 months after PTA. Secondary endpoints included clinical and hemodynamic assessment. RESULTS: Restenosis in patients undergoing EVBT was 17% (23/133) versus 35% (50/142) in patients without EVBT (p<0.001); in patients treated with probucol versus placebo, the rates were 23% (31/135) and 30% (43/140, p<0.001). Three quarters (77%, 102/133) of patients were free of claudication after EVBT therapy versus 61% (87/142) without EVBT (p<0.05). Need for target vessel revascularization was 6% (8/133) with EVBT versus 14% (20/142) without EVBT (p<0.01). Late thrombotic occlusions occurred in 4% (6/133), exclusively in patients treated with EVBT after stent implantation. CONCLUSIONS: Endovascular brachytherapy significantly reduces restenosis, improves symptoms, and reduces reinterventions after PTA of femoropopliteal arteries. Probucol reduces restenosis but has no additive effect when combined with brachytherapy.

Vinorelbine plus low-dose cisplatinum with concomitant radiotherapy for the treatment of locally advanced or inoperable non-metastasized non-small-cell lung cancer (stage I-IIIB): a phase II study.

In a phase II study, we assessed the toxicity and efficacy of daily low-dose cisplatin (6 mg/m2) and weekly vinorelbine (15 mg/m2) with concurrent thoracic irradiation (60 Gy) for locally advanced non-metastasized non-small-cell lung cancer. The overall response rate was 65%, complete response 12% and the median overall survival was 64 weeks.

Concomitant cisplatin significantly improves locoregional control in advanced head and neck cancers treated with hyperfractionated radiotherapy.

PURPOSE: To determine whether the application of two courses of cisplatin simultaneously with hyperfractionated radiotherapy improves the outcome in locally advanced and/or node-positive nonmetastatic carcinomas of the head and neck, compared with hyperfractionated radiotherapy alone. PATIENTS AND METHODS: From July 1994 to July 2000, 224 patients with squamous cell carcinomas of the head and neck (excluding nasopharynx and paranasal sinus) were randomly assigned to hyperfractionated radiotherapy (median dose, 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20 mg/m2 on 5 days of weeks 1 and 5). The primary end point was time to any treatment failure; secondary end points were locoregional failure, metastatic relapse, overall survival, and late toxicity. RESULTS: There was no difference in radiotherapy between both treatment arms (74.4 Gy in 44 days). The full cisplatin dose was applied in 93% and 71% of patients during the first and second treatment cycles, respectively. Acute toxicity was similar in both arms. Median time to any treatment failure was not significantly different between treatment arms (19 months for combined treatment and 16 months for radiotherapy only, respectively) and the failure-free rate at 2.5 years was 45% and 33%, respectively. Locoregional control and distant disease-free survival were significantly improved with cisplatin (log-rank test, P = .039 and .011, respectively). The difference in overall survival did not reach significance (log-rank test, P = .147). Late toxicity was comparable in both treatment groups. CONCLUSION: The therapeutic index of hyperfractionated radiotherapy is improved by concomitant cisplatin.