title: Thymidine phosphorylase expression in metastatic sites is predictive for response in patients with colorectal cancer treated with continuous oral capecitabine and biweekly oxaliplatin.
abstract: The primary objective of this study was to determine the activity and safety profile of biweekly oxaliplatin combined with continuous oral capecitabine in the first-line treatment of metastatic colorectal cancer. A secondary endpoint was to investigate the correlation between thymidylate synthase and thymidine phosphorylase (TP) expression in metastatic tissues and tumor response. Forty-one patients received oral capecitabine 1331 mg/m every day combined with intravenous oxaliplatin 85 mg/m every 2 weeks. The overall response rate was 58.5% [95% confidence interval (CI): 43.3-73.6%], the median progression-free survival 9.4 months (95% CI: 7.7-11.2 months) and the median survival 22.3 months (95% CI: 16.1-27.5 months). There were no grade 4 toxicities, and grade 3 toxicity was also uncommon. High TP expression in metastatic tissue was significantly associated with response to treatment (P=0.019), and also with a trend towards a better median progression-free survival and overall survival compared with patients expressing low TP (P=0.056; P=0.073). This study suggests that biweekly oxaliplatin and continuous oral capecitabine is an active and well-tolerated chemotherapy regimen in the first-line treatment of metastatic colorectal cancer. Moreover, these findings add to a growing body of evidence that patients with high levels of intratumoral TP expression are the ideal candidates for capecitabine-based chemotherapy.
authors.affiliation: Medical Oncology Section, Department of Pharmacology, University of Siena, Siena, Italy. r.petrioli@ao-siena.toscana.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Petrioli
authors.forename: Gianluca
authors.initials: G
authors.lastname: Bargagli
authors.forename: Stefano
authors.initials: S
authors.lastname: Lazzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pascucci
authors.forename: Edoardo
authors.initials: E
authors.lastname: Francini
authors.forename: Cristiana
authors.initials: C
authors.lastname: Bellan
authors.forename: Raffaele
authors.initials: R
authors.lastname: Conca
authors.forename: Ignazio
authors.initials: I
authors.lastname: Martellucci
authors.forename: Anna Ida
authors.initials: AI
authors.lastname: Fiaschi
authors.forename: Bruno
authors.initials: B
authors.lastname: Lorenzi
authors.forename: Guido
authors.initials: G
authors.lastname: Francini
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077150:Oxaliplatin; D011379:Prognosis; D013939:Thymidine Phosphorylase / Q000096:biosynthesis*; D013940:Thymidylate Synthase / Q000096:biosynthesis
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D013940:Thymidylate Synthase; D013939:Thymidine Phosphorylase; D005472:Fluorouracil