title: Clinical efficacy and predictive molecular markers of neoadjuvant gemcitabine and pemetrexed in resectable non-small cell lung cancer.
abstract: BACKGROUND
  A trial of neoadjuvant gemcitabine and pemetrexed (GP) chemotherapy in patients with resectable non-small cell lung cancer was conducted. The goal was to achieve a disease response rate of 50% and to determine if the expression levels of genes associated with GP metabolism are predictive of response.
  
  
  METHODS
  Patients had staging with a computed tomography scan, whole body F-18 fluorodeoxyglucose positron emission tomography, and mediastinoscopy. Four biweekly cycles of GP were given. Patients were restaged, and those with resectable stage IB-III disease had thoracotomy. Fresh frozen tumor specimens were collected before and after chemotherapy and the mRNA levels of 14 target genes determined by real-time reverse transcription polymerase chain reaction.
  
  
  RESULTS
  Fifty-two patients started therapy. The radiographic disease response rate was 35% (95% confidence interval 21.7-49.6%), and the progression rate was 6%. Forty-six patients had a thoracotomy. The complete tumor resection rate was 77% (40/52). There were no perioperative deaths or deaths related to chemotherapy. Tumor response to chemotherapy was inversely correlated with the level of expression of RRM1 (p < 0.001; regulatory subunit of ribonucleotide reductase) and TS (p = 0.006; thymidylate synthase); i.e., the reduction in tumor size was greater in those with low levels of expression.
  
  
  CONCLUSIONS
  Neoadjuvant GP is well tolerated and produces an objective response rate of 35%. Tumoral RRM1 and TS mRNA levels are predictive of disease response and should be considered as parameters for treatment selection in future trials with this regimen.
authors.affiliation: Program and Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida, USA. gerold.bepler@moffitt.org
authors.forename: Gerold
authors.initials: G
authors.lastname: Bepler
authors.forename: K Eric
authors.initials: KE
authors.lastname: Sommers
authors.forename: Alan
authors.initials: A
authors.lastname: Cantor
authors.forename: Xueli
authors.initials: X
authors.lastname: Li
authors.forename: Anupama
authors.initials: A
authors.lastname: Sharma
authors.forename: Charles
authors.initials: C
authors.lastname: Williams
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiappori
authors.forename: Eric
authors.initials: E
authors.lastname: Haura
authors.forename: Scott
authors.initials: S
authors.lastname: Antonia
authors.forename: Tawee
authors.initials: T
authors.lastname: Tanvetyanon
authors.forename: George
authors.initials: G
authors.lastname: Simon
authors.forename: Coleman
authors.initials: C
authors.lastname: Obasaju
authors.forename: Lary A
authors.initials: LA
authors.lastname: Robinson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000601:surgery; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D000068437:Pemetrexed; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D005971:Glutamates; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000093542:Gemcitabine