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I appreciate the correspondents' interest in our article1 and their suggestion that the lack of activity seen with imatinib in small cell lung carcinoma (SCLC) may be due to a discrepancy between c-kit expression in primary tumors and its expression in metastases, which may have altered expression due to mutations or prior treatment. This concept also has been proposed by an Italian group that evaluated 27 SCLC biopsy samples before and after treatment with etoposide and cisplatin.2 At diagnosis, 78% of patients in that study demonstrated kit overexpression by immunohistochemistry, whereas only 48% maintained kit overexpression after treatment. Although this suggests that a decrease in kit expression occurs after chemotherapy treatment, enough kit expression seems to be maintained that, if this was the prerequisite for response with imatinib in SCLC, then some level of activity still would be observed. Furthermore, it has been shown that imatinib lacks activity in previously untreated patients,3 further countering this argument.

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