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Published on: October 23, 2019
Imatinib mesylate lacks activity in small cell lung carcinoma expressing c-kit protein: a phase II clinical trial
Lee M Krug1, John P Crapanzano, Christopher G Azzoli
1Thoracic Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, New York, New York 10021, USA. krugl@mskcc.org
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.
Insights
Imatinib did not show antitumor activity in patients with recurrent small cell lung carcinoma (SCLC) expressing c-kit protein. Further research is needed to find effective therapies for this aggressive cancer.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Imatinib targets c-kit tyrosine kinase, effective in gastrointestinal stromal tumors.
- C-kit protein expression in small cell lung carcinoma (SCLC) suggests a potential therapeutic target.
- Rationale for investigating imatinib in recurrent SCLC based on c-kit expression and in vitro data.
Purpose of the Study:
- To evaluate the efficacy of imatinib in patients with recurrent SCLC and c-kit protein expression.
- To assess the safety and tolerability of imatinib in this patient population.
Main Methods:
- Phase II, single-institution study.
- Patients with progressive SCLC after chemotherapy had tumor specimens screened for c-kit protein (CD117).
- Eligible patients received imatinib 800 mg/day; 12 patients were enrolled.
Main Results:
- C-kit protein was present in 78% of 36 assessable SCLC tumor samples.
- No objective responses were observed in the 12 treated patients.
- All patients experienced disease progression by Week 4; common toxicities included edema, fatigue, and nausea.
Conclusions:
- Imatinib demonstrated no antitumor activity in SCLC patients with c-kit protein expression.
- The poor prognosis for advanced SCLC underscores the need for novel therapeutic strategies.
- Further studies are crucial to identify effective treatments for SCLC.
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