Effect of tyrosine kinase inhibitors on wound healing and tissue repair: implications for surgery in cancer patients.

ABSTRACT

Small-molecule tyrosine kinase inhibitors (TKIs) represent a major advance in the treatment of certain forms of cancer. Unexpectedly, however, their use is associated with serious toxic effects on many vital organs and functions. Some of these effects, such as venous thromboembolism, haemorrhage, gastric perforation and a potential for impaired tissue healing, have direct implications for the safety of surgery in cancer patients. A number of currently approved TKIs are suspected or have been reported to impair wound healing but, understandably, there have been no formal pre- or post-approval clinical trials to evaluate the extent of the risk. Consequently, drug labels typically recommend discontinuation of the TKI concerned prior to elective surgery. In patients with gastric perforation, permanent discontinuation is advised. These recommendations, which are based on a precautionary principle, raise a dilemma, especially in patients with TKI-responsive tumours. This review focuses on the labelled potential of these novel antineoplastic agents to impair tissue repair and wound healing, and the evidence concerning the likely mechanisms involved. At present, because of the lack of formal clinical data, there are no evidence-based guidelines on the management of surgery in patients treated with TKIs. There is a need for a central registry of clinical outcomes following emergency surgery in cancer patients receiving TKIs and TKI-naïve matched controls. Analysis of outcomes data from such registries will assist in formulating guidelines on the management of elective surgery in TKI-treated patients. If TKIs are shown to significantly impair wound healing, patients receiving TKI therapy will require special monitoring and a collaborative approach between oncologists and surgeons for individualized reappraisal of the risk/benefit of the TKI treatment.