Imatinib mesylate lacks activity in small cell lung carcinoma expressing c-kit protein: A phase II clinical trial Journal Article
| Authors: | Krug, L. M.; Crapanzano, J. P.; Azzoli, C. G.; Miller, V. A.; Rizvi, N.; Gomez, J.; Kris, M. G.; Pizzo, B.; Tyson, L.; Dunne, M.; Heelan, R. T. |
| Article Title: | Imatinib mesylate lacks activity in small cell lung carcinoma expressing c-kit protein: A phase II clinical trial |
| 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. © 2005 American Cancer Society. |
| Keywords: | adult; cancer chemotherapy; clinical article; protein expression; middle aged; treatment failure; clinical trial; fatigue; neutropenia; diarrhea; hypophosphatemia; risk benefit analysis; side effect; antineoplastic agents; c-kit; gastrointestinal stromal tumor; imatinib; stem cell factor; proto-oncogene proteins c-kit; edema; phase 2 clinical trial; neoplasm recurrence, local; anemia; leukopenia; nausea; thrombocytopenia; vomiting; lung neoplasms; antineoplastic activity; pyrimidines; protein kinase inhibitors; immunoenzyme techniques; hypokalemia; hyponatremia; lung small cell cancer; gene expression regulation, neoplastic; disease progression; autocrine effect; paracrine signaling; protein-tyrosine kinases; piperazines; tumor growth; cancer control; hypocalcemia; small cell lung carcinoma; growth inhibition; carcinoma, small cell |
| Journal Title: | Cancer |
| Volume: | 103 |
| Issue: | 10 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2005-05-15 |
| Start Page: | 2128 |
| End Page: | 2131 |
| Language: | English |
| DOI: | 10.1002/cncr.21000 |
| PUBMED: | 15812822 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 91" - "Export Date: 24 October 2012" - "CODEN: CANCA" - "Source: Scopus" |
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