Gemcitabine plus conventional-dose epirubicin versus gemcitabine plus cisplatin as first-line chemotherapy for stage IIIB/IV non-small cell lung carcinoma--a randomized phase II trial.
BACKGROUND
Epirubicin was effective for the treatment of non-small cell lung carcinoma (NSCLC). This study compared the efficacy and safety of gemcitabine plus conventional-dose epirubicin (GE) with gemcitabine-cisplatin (GC) as first-line chemotherapy for stage IIIB/IV NSCLC and evaluated the predictive value of nuclear expression of excision repair cross-complementing group 1 (ERCC1) and topoisomerase IIalpha (TopoIIalpha) on treatment outcome.


METHODS
Patients were randomized to GE (gemcitabine, 1000mg/m(2) on days 1, 8, and 15 and epirubicin, 70mg/m(2) on day 15) or GC (gemcitabine, 1000mg/m(2) on days 1, 8, and 15 and cisplatin, 80mg/m(2) on day 15). Treatment cycles were repeated every 4 weeks. Immunohistochemical study of ERCC1 and TopoIIalpha was done for patients with available tumor specimens.


RESULTS
The response rate was 31.0% (95% CI 16.4-45.5%) for GC (n=41) and 37.2.0% (95% CI 22.2-52.3%) for GE (n=39). No significant differences in median time-to-treatment-failure (TTF) (GC, 6.1 months; GE, 6.2 months) or overall survival (GC, 13.2 months; GE, 21.5 months) were found between the two arms. Grade 3/4 neutropenia and febrile neutropenia were more common in GE. However, delay of protocol treatment due to leukopenia was similar between the two arms. Patients with expression of both ERCC1 and TopoIIalpha had a significantly shorter TTF (median 2.4 months, 95% CI 0.7-4.1 months) than other patients (median 8.8 months, 95% CI 5.8-11.8 months) (p=0.04).


CONCLUSIONS
GE regimen is effective and well-tolerated for NSCLC patients. Expression of both ERCC1 and TopoIIalpha may be associated with poor response to chemotherapy.
Hsu
Chiun
C
Department of Oncology, National Taiwan University Hospital, 7, Chung-Shan South Road, Taipei, 100, Taiwan.
Kuo
Sung-Hsin
SH
Hu
Fu-Chang
FC
Cheng
Ann-Lii
AL
Shih
Jin-Yuan
JY
Yu
Chong-Jen
CJ
Lin
Chia-Chi
CC
Huang
Tsu-Chen
TC
Yang
Pan-Chyr
PC
Yang
Chih-Hsin
CH
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004720:Endonucleases / Q000378:metabolism; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D003841:Deoxycytidine; D015251:Epirubicin; C071447:ERCC1 protein, human; D004720:Endonucleases; D004250:DNA Topoisomerases, Type II; D002945:Cisplatin; D000093542:Gemcitabine