Preclinical assessment of cisplatin-based therapy versus docetaxel-based therapy on a panel of human non-small-cell lung cancer xenografts.
The success of treatment of advanced non-small-cell lung cancer (NSCLC) remains very poor. The aim of this study was, on a series of NSCLC xenografts, to compare the efficacy of standard cisplatin-based or docetaxel-based chemotherapy. Seven human xenografts were obtained from six patients (two xenografts were derived from primary or metastatic tumors of the same patient). Three xenografts were adenocarcinomas and four were squamous cell carcinomas. All xenografts reproduced the same histology as that of the patient's original tumor. Docetaxel, administered as single-agent chemotherapy, induced a significant response in five of the seven NSCLC xenografts (71%), without significant increase after combination with cisplatin, vinorelbine, or gemcitabine. Relative expression of genes putatively involved in drug response was also studied in all xenografts and did not explain the variability of drug sensitivity. In conclusion, this panel of human NSCLC xenografts reliably reproduces the data obtained in patient tumors and the relative sensitivity to docetaxel reported in NSCLC patients.
Némati
Fariba
F
Preclinical Investigation Laboratory, Department of Translational Research, Hôpital Européen Georges Pompidou, Paris, France.
Bras-Gonçalves
Rui
R
Fontaine
Jean-Jacques
JJ
de Pinieux
Gonzague
G
De Cremoux
Patricia
P
Chapelier
Alain
A
Daniel
Catherine
C
Laurent-Puig
Pierre
P
Livartowski
Alain
A
Judde
Jean-Gabriel
JG
Bordier
Vincent
V
Poupon
Marie-France
MF
Decaudin
Didier
D
D000368:Aged; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin