Expression of genes related to activity of oxaliplatin and 5-fluorouracil in endoscopic biopsies of primary esophageal cancer in patients receiving oxaliplatin, 5-flourouracil and radiation: characterization and exploratory analysis with survival.
With a goal of identifying relations between gene expression and response (mucosal or pathological) or survival in esophageal cancer patients (stages II to IV) receiving oxaliplatin, 5-fluorouracil (5FU) and radiation, we measured in endoscopic primary tumor biopsies from 38 patients, the expression of seven genes (gammaGCS, gammaGT, MRP-2, ERCC-1, XPA, TS and DPD) prior to treatment, 1 week following oxaliplatin alone and at the end of the combined radio-chemotherapy cycle using real time QRT-PCR. A higher pretreatment level of XPA was related to shorter survival with a hazard ratio of 2.43 (90% confidence interval 1.09 to 5.43) using Cox regression modeling. However, multivariate analysis with a Cox model indicated low expression of XPA or TS and combined stages II and III had a higher probability of survival (for XPA: hazard ratio 3.0 and 90% C.I. of 1.3 to 6.9, with adjustment for stage included; for TS: hazard ratio is 1.98 with 90% C.I. of 0.94 to 4.20. The expression of TS, gammaGCS, ERCC-1 and MRP-2 declined from D 1 to the end of the cycle (p<0.05, sign test). A validation and further understanding of the findings need to be carried out in a larger study with a more homogeneous population of patients.
Leichman
L
L
Aptium Oncology, Comprehensive Cancer Center of the Desert, Palm Springs, CA, USA.
Lawrence
D
D
Leichman
C G
CG
Nava
H
H
Nava
E
E
Proulx
G
G
Clark
K
K
Khushalani
N I
NI
Berdzik
J
J
Greco
W
W
Smith
P
P
Creaven
P J
PJ
Kepner
J L
JL
Javle
M M
MM
Pendyala
L
L
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001706:Biopsy / Q000379:methods; D003131:Combined Modality Therapy; D016145:Endoscopy, Digestive System; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007820:Laryngeal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000077150:Oxaliplatin; D011829:Radiation Dosage; D016019:Survival Analysis; D016896:Treatment Outcome
C000715087:ABCC2 protein, human; D000089762:Multidrug Resistance-Associated Protein 2; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil