title: Transcripts in pretreatment biopsies from a three-arm randomized trial in metastatic non-small-cell lung cancer.
abstract: Non-small-cell lung cancer patients with locally advanced or metastatic disease at the time of diagnosis show marginal response to chemotherapy in terms of tumor shrinkage, time to progression and median survival. The identification and implementation of predictive genetic markers of response-specific cytotoxic drugs is a priority of current research and future trials. In this study, we have used quantitative PCR to analyse expression of beta-tubulin III, stathmin, RRM1, COX-2 and GSTP1 in mRNA isolated from paraffin-embedded tumor biopsies of 75 nonsmall-cell lung cancer patients treated as part of a large randomized trial. In total, 22 patients were treated with gemcitabine/cisplatin, 25 with vinorelbine/cisplatin and 28 with paclitaxel/carboplatin. There were no differences in clinical characteristics and transcript levels in the pretreatment biopsies according to treatment arm. Patients with low beta-tubulin III levels had better response in the paclitaxel/carboplatin arm (P=0.05), and those with low RRM1 levels showed a tendency to better response in the gemcitabine/cisplatin arm. Time to progression was influenced by beta-tubulin III (P=0.03) and stathmin (P=0.05) levels in the vinorelbine/cisplatin arm, and there was a tendency toward correlation between beta-tubulin III levels and time to progression in the paclitaxel/carboplatin arm. RRM1 levels influenced time to progression (P=0.05) and even more so, survival (P=0.0028) in the gemcitabine/cisplatin arm. The predictive value of beta-tubulin III, stathmin and RRM1 should be tested in prospective customized chemotherapy trials, the results of which will help tailor chemotherapy to improve patient survival.
authors.affiliation: Department of Oncology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scagliotti
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Danenberg
authors.forename: Reginald V N
authors.initials: RV
authors.lastname: Lord
authors.forename: Gerold
authors.initials: G
authors.lastname: Bepler
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
authors.forename: Janine
authors.initials: J
authors.lastname: Cooc
authors.forename: Lucio
authors.initials: L
authors.lastname: Crinò
authors.forename: José Javier
authors.initials: JJ
authors.lastname: Sánchez
authors.forename: Miquel
authors.initials: M
authors.lastname: Taron
authors.forename: Corrado
authors.initials: C
authors.lastname: Boni
authors.forename: Filippo
authors.initials: F
authors.lastname: De Marinis
authors.forename: Maurizio
authors.initials: M
authors.lastname: Tonato
authors.forename: Maurizio
authors.initials: M
authors.lastname: Marangolo
authors.forename: Felice
authors.initials: F
authors.lastname: Gozzelino
authors.forename: Franceso
authors.initials: F
authors.lastname: Di Costanzo
authors.forename: Massimo
authors.initials: M
authors.lastname: Rinaldi
authors.forename: Dennis
authors.initials: D
authors.lastname: Salonga
authors.forename: Craig
authors.initials: C
authors.lastname: Stephens
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000235:genetics; D001706:Biopsy; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D051546:Cyclooxygenase 2; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008565:Membrane Proteins; D008868:Microtubule Proteins; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D010750:Phosphoproteins / Q000235:genetics; D011237:Predictive Value of Tests; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D012262:Ribonucleoside Diphosphate Reductase; D050777:Stathmin; D015996:Survival Rate; D014158:Transcription, Genetic; D014404:Tubulin / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D007527:Isoenzymes; D008565:Membrane Proteins; D008868:Microtubule Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C493995:STMN1 protein, human; D050777:Stathmin; D014404:Tubulin; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; D014747:Vinblastine; D016190:Carboplatin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D017239:Paclitaxel; D002945:Cisplatin; D000077235:Vinorelbine; D000093542:Gemcitabine