Phase II study of imatinib in patients with small cell lung cancer.
OBJECTIVE
The purpose of our study was to assess the objective response to imatinib administered to patients with small cell lung cancer (SCLC).


METHODS
Eligible patients were those with SCLC who either had chemotherapy-naive extensive-stage or had SCLC in a sensitive relapse. Patients enrolled on the trial were treated with 600 mg of imatinib daily. The response was assessed using Southwest Oncology Group (SWOG) criteria after 3 and 6 weeks. Tumor specimens were examined by immunohistochemistry for the KIT receptor.


RESULTS
Nineteen patients with SCLC entered on the study, including 16 men and 3 women. Nine patients had previously untreated extensive-stage disease and 10 patients had sensitive relapse. A central pathology review confirmed SCLC in only 14 of the 19 patients. There were no objective responses; however, one patient with sensitive-relapse disease had prolonged stabilization of disease (>3 months) while on imatinib therapy. The median time to progression was 0.8 months (range, 0.6-1.3 months) and 1.2 months (range, 0.2-4.1 months) in the previously untreated and sensitive-relapse groups, respectively. Tumor tissue samples from 4 (21%) of the 19 patients had the KIT receptor (CD117).


CONCLUSIONS
There was no observed antitumor activity in this limited Phase II trial of patients with SCLC, of which only a few tumors showed expression of the imatinib target. The results of this trial are, thus, inconclusive about the antitumor activity of imatinib against SCLC with the targeted KIT receptor (CD117). Further testing of imatinib in patients with SCLC will focus on demonstration of KIT expression in the setting of confirmed SCLC histology.
Johnson
Bruce E
BE
Dana Farber Cancer Institute, Brigham and Women's Hospital and Massachusetts General Hospital, Boston, Massachusetts 02115, USA. BEJohnson@Partners.org
Fischer
Thomas
T
Fischer
Berthold
B
Dunlop
David
D
Rischin
Danny
D
Silberman
Sandra
S
Kowalski
Mildred Ortu
MO
Sayles
Deanne
D
Dimitrijevic
Sasa
S
Fletcher
Christopher
C
Hornick
Jason
J
Salgia
Ravi
R
Le Chevalier
Thierry
T
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D010879:Piperazines / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects* / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit