Evidence for epidermal growth factor receptor-enhanced chemosensitivity in combinations of cisplatin and the new irreversible tyrosine kinase inhibitor CI-1033

Irreversible inhibitors of the epidermal growth factor receptor (EGFR) are showing promise in clinical trials. This report is the first to show that inhibition of the EGFR tyrosine kinase by an irreversible binder synergizes with cisplatin, at least in EGFR-overexpressing tissue culture cell lines in vitro. Unlike previous synergies demonstrated between ErbB2 blockade and DNA-damaging drugs, the synergy between the irreversible EGFR inhibitor and cisplatin does not appear to involve the repair of DNA-cisplatin adducts. Given the current clinical data, this combination may be of more than theoretical interest.