Multicenter phase II trial of gefitinib first-line therapy followed by chemotherapy in advanced non-small-cell lung cancer (NSCLC): SAKK protocol 19/03.
BACKGROUND
Gefitinib is active in patients with pretreated non-small-cell lung cancer (NSCLC). We evaluated the activity and toxicity of gefitinib first-line treatment in advanced NSCLC followed by chemotherapy at disease progression.


METHODS
In all, 63 patients with chemotherapy-naive stage IIIB/IV NSCLC received gefitinib 250 mg/day. At disease progression, gefitinib was replaced by cisplatin 80 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1, 8 for up to six 3-week cycles. Primary end point was the disease stabilization rate (DSR) after 12 weeks of gefitinib.


RESULTS
After 12 weeks of gefitinib, the DSR was 24% and the response rate (RR) was 8%. Median time to progression (TtP) was 2.5 months and median overall survival (OS) 11.5 months. Never smokers (n = 9) had a DSR of 56% and a median OS of 20.2 months; patients with epidermal growth factor receptor (EGFR) mutation (n = 4) had a DSR of 75% and the median OS was not reached after the follow-up of 21.6 months. In all, 41 patients received chemotherapy with an overall RR of 34%, DSR of 71% and median TtP of 6.7 months.


CONCLUSIONS
First-line gefitinib monotherapy led to a DSR of 24% at 12 weeks in an unselected patients population. Never smokers and patients with EGFR mutations tend to have a better outcome; hence, further trials in selected patients are warranted.
D'Addario
G
G
Department of Oncology, Kantonsspital St.Gallen, St. Gallen, Switzerland. g.daddario@hin.ch
Rauch
D
D
Stupp
R
R
Pless
M
M
Stahel
R
R
Mach
N
N
Jost
L
L
Widmer
L
L
Tapia
C
C
Bihl
M
M
Mayer
M
M
Ribi
K
K
Lerch
S
S
Bubendorf
L
L
Betticher
D C
DC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011788:Quality of Life; D011799:Quinazolines / Q000627:therapeutic use*; D011859:Radiography; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D011795:Surveys and Questionnaires; D013557:Switzerland; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics; D000093542:Gemcitabine
D000970:Antineoplastic Agents; C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D003841:Deoxycytidine; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D002945:Cisplatin; D000077156:Gefitinib; D000093542:Gemcitabine