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001). The lack of an effect associated with thalidomide was also observed in a large trial of 724 patients with small cell lung cancer.21 VEGF may be superfluous in advanced lung cancer where tumour vasculatures are already established. Angiogenesis at the late stage may be governed by pro-angiogenic factors other than VEGF, which can explain why antagonizing VEGF (e.g. with bevacizumab) or its receptors is ineffective. Targeting multiple angiogenic pathways may be necessary in late-stage lung cancer. Emerging evidence suggests that the efficacy of anti-angiogenic agents is also dependent on the cytotoxic agents they are combined with.22,23 There are increasing numbers of alternatives to anti-angiogeneic drugs for patients with non-squamous NSCLC. Cetuximab, an mAb targeting the epidermal growth factor receptor, in combination with vinorelbine http://www.selleckchem.com/products/Neratinib(HKI-272).html and cisplatin, increased survival in the First-line Erbitux in Lung Cancer study and was https://en.wikipedia.org/wiki/Quinapyramine effective against all subtypes of NSCLC, an advantage over bevacizumab.24 The median survival was 1?year for adenocarcinoma in a subgroup analysis. This is the first phase III trial demonstrating benefit with a combination of an epidermal growth factor receptor inhibitor and chemotherapy for a general lung cancer population.24�C28 Pemetrexed, in combination with cisplatin, has also been shown to significantly improve survival in patients with non-squamous NSCLC, when compared with cisplatin and gemcitabine therapy (12.6 vs 10.9?months; HR?=?0.84).29 This benefit is similar to that seen with ECOG 4599 without bevacizumab. In the JMDB study, maintenance pemetrexed after four cycles of first-line chemotherapy (not including pemetrexed) also significantly improved median progression-free (4.3 vs 2.6?months; HR?=?0.50, P? http://www.selleckchem.com/products/Roscovitine.html now available, including pemetrexed, cetuximab, gefitinib and erlotinib, which are also capable of improving survival beyond 1?year. Paul Baas, MD, PhD This Pro/Con debate has highlighted the controversy regarding the indication and role of anti-angiogenic agents in NSCLC management. In particular, the impact of bevacizumab as the only registered anti-angiogenic drug available for NSCLC has been discussed. The pre-clinical evidence is overwhelmingly positive for the use of anti-angiogenic agents in the treatment of a wide range of cancer.