In this study, the costs of managing adverse events associated with these therapies in the United Kingdom, Germany, France and Italy were considerably higher for sunitinib than for bevacizumab plus IFN. Modification of basic clinical and economic assumptions (hospitalisation costs Abiraterone mw and the main cost-driving adverse events) showed that the model remained stable over the entire range of plausible values for a given parameter, and was therefore robust. The main cost drivers for sunitinib were lymphopaenia, neutropaenia, thrombocytopaenia, leucopaenia and fatigue/asthaenia. In contrast, the main cost drivers for the management of adverse events associated with bevacizumab plus IFN were fatigue/asthaenia, proteinuria, bleeding, anaemia and GI perforation.

The majority of the increased cost associated with sunitinib was related to the management of haematological toxicities, which accounted for little or none of the cost of managing adverse events associated with bevacizumab plus IFN; chemotherapy-related haematological adverse events are associated with an economic burden due to costly hospitalisation/treatment costs and negatively affect patient quality of life (Elliott, 1996; Liou et al, 2007). This study also suggests that sunitinib involves higher costs for the management of adverse events that patients perceive as troublesome and affect their everyday activities and well-being. For example, hand-foot syndrome with sunitinib often manifests 3�C4 weeks after treatment initiation (Hutson et al, 2008); it occurs predominantly on pressure points on the hands and feet, making walking and manual and sporting activities difficult.

In addition, GI disorders (e.g., diarrhoea and mucosal inflammation) are common with sunitinib and can often be uncomfortable and embarrassing for the patient, interrupting daily activities (e.g., work), as well as interfering with nutrition in patients who may already be compromised in this regard. The management strategies available for dealing with Brefeldin_A adverse events due to sunitinib and bevacizumab plus IFN may also be relevant when choosing first-line treatment for RCC. Reducing the dose of IFN used in combination with bevacizumab substantially improves the tolerability and management of IFN-related adverse events, enabling patients to remain on therapy while maintaining efficacy (Melichar et al, 2008). These promising data derived from a retrospective analysis of AVOREN need to be confirmed, most likely from the ongoing prospective phase II trial of bevacizumab plus 3 MIU IFN (BEVLiN). The ability to improve tolerability by using lower doses of IFN in combination with bevacizumab provides even greater cost savings compared with sunitinib in the first-line treatment of metastatic RCC (Mickisch et al, 2009).