Imatinib mesylate lacks activity in small cell lung carcinoma expressing c‐kit protein A Phase II clinical trial

• Published in: Cancer Vol. 103; no. 10; pp. 2128 - 2131
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: New York, NY Wiley-Liss 15.05.2005
• Subjects: Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Benzamides; Biological and medical sciences; Carcinoma, Small Cell - drug therapy; Carcinoma, Small Cell - metabolism; Disease Progression; Edema - chemically induced; Fatigue - chemically induced; Female; Gene Expression Regulation, Neoplastic; Humans; Imatinib Mesylate; Immunoenzyme Techniques; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Male; Medical sciences; Middle Aged; Nausea - chemically induced; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - metabolism; Piperazines - adverse effects; Piperazines - therapeutic use; Pneumology; Prognosis; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Protein-Tyrosine Kinases - antagonists & inhibitors; Proto-Oncogene Proteins c-kit - analysis; Proto-Oncogene Proteins c-kit - genetics; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Treatment Failure; Tumors; Tumors of the respiratory system and mediastinum; Antineoplastic agent; Lung disease; Imatinib; Respiratory disease; Enzyme; Kit protein; c-kit; Transferases; Bonchopulmonary small cell carcinoma; Lung cancer; Enzyme inhibitor; Activity; Protein C; Malignant tumor; small cell lung carcinoma; Cancerology; C-Onc gene; Phase II trial; Bronchus disease; kit Gene; Protein-tyrosine kinase
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.21000

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. 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). 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. 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.