Thymidine phosphorylase expression in metastatic sites is predictive for response in patients with colorectal cancer treated with continuous oral capecitabine and biweekly oxaliplatin.
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.
Petrioli
Roberto
R
Medical Oncology Section, Department of Pharmacology, University of Siena, Siena, Italy. r.petrioli@ao-siena.toscana.it
Bargagli
Gianluca
G
Lazzi
Stefano
S
Pascucci
Alessandra
A
Francini
Edoardo
E
Bellan
Cristiana
C
Conca
Raffaele
R
Martellucci
Ignazio
I
Fiaschi
Anna Ida
AI
Lorenzi
Bruno
B
Francini
Guido
G
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
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D013940:Thymidylate Synthase; D013939:Thymidine Phosphorylase; D005472:Fluorouracil