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Imatinib mesylate lacks activity in small cell lung carcinoma expressing c‐kit protein
Author(s) -
Krug Lee M.,
Crapanzano John P.,
Azzoli Christopher G.,
Miller Vincent A.,
Rizvi Naiyer,
Gomez Jorge,
Kris Mark G.,
Pizzo Barbara,
Tyson Leslie,
Dunne Megan,
Heelan Robert T.
Publication year - 2005
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.21000
Subject(s) - medicine , imatinib , imatinib mesylate , cd117 , population , tyrosine kinase inhibitor , pathology , oncology , cancer , cancer research , biology , stem cell , myeloid leukemia , environmental health , cd34 , genetics
Abstract BACKGROUND Imatinib inhibits the c‐kit tyrosine kinase, which, accounts for its activity in gastrointestinal stromal tumors. The presence of c‐kit protein expression in small cell lung carcinoma (SCLC) tumor specimens, as well as in vitro data supporting the role of c‐kit in autocrine and paracrine growth stimulation specifically in SCLC, provided a rationale for studying imatinib in this disease. The authors conducted a Phase II single‐institution study of imatinib in patients with recurrent SCLC whose tumor specimens expressed c‐kit protein. METHODS Patients with progressive SCLC after one or two previous chemotherapy regimens consented to have their tumor specimens screened by immunoperoxidase stain (CD117, Dako Corporation, Carpinteria, CA) for c‐kit protein expression. If present, individuals were then eligible for treatment with an imatinib dose of 400 mg orally twice daily (total, 800 mg per day). RESULTS The presence of c‐kit protein was assessable in 36 of 39 (92%) tumor samples. Twenty‐eight (78%) tumor samples had immunohistochemical staining for c‐kit protein. Twelve patients were enrolled in the treatment portion of the current study. No responses were observed, and all patients had disease progression by Week 4. Edema, fatigue, nausea, and electrolyte abnormalities were the primary toxicities. CONCLUSIONS Imatinib did not have antitumor activity against SCLC, even with c‐kit protein present in tumor specimens. The dismal prognosis for these patients with progressive SCLC emphasized the urgent need for continued studies of new therapies in this population. Cancer 2005. © 2005 American Cancer Society.