550P - TP, TS and DPD as potential predictors of outcome following capecitabine plus oxaliplatin (XELOX) vs. Bolus 5-fluorouracil/leucovorin (5-FU/LV) as a...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Biomarkers
Colon Cancer
Presenter Hans-Joachim Schmoll
Authors H. Schmoll1, J. Tabernero2, J.A. Maroun3, F.G.M. De Braud4, T.J. Price5, E. Van Cutsem6, M. Hill7, S. Hoersch8, K. Rittweger9, D. Haller10
  • 1Internal Medicine, University Clinic Halle (Saale), Halle/DE
  • 2Medical Oncology, Vall d’Hebron University Hospital, Barcelona/ES
  • 3Medical Oncology, The Ottawa Hospital Regional Cancer Centre, K1H 8L6 - Ottawa/CA
  • 4Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Milano/IT
  • 5Oncology, The Queen Elizabeth Hospital, Adelaide/AU
  • 6Digestive Oncology, University Hospital Gasthuisberg/Leuven, Leuven/BE
  • 7Medical Oncology, Kent Oncology Centre, Maidstone/UK
  • 8Biostatistics, Dr. Manfred Köhler GmbH; working on behalf of Roche PDBB (Biostatistics), Freiburg/DE
  • 9Global Development, Hoffmann-La Roche Inc., Nutley/US
  • 10Hematology/oncology, University of Pennsylvania, Philadelphia/US



In NO16968, XELOX was superior in terms of disease-free survival (DFS) and overall survival (OS) to bolus 5-FU/LV as adjuvant therapy for stage III colon cancer [Schmoll et al. ASCO GI 2012]. Three key enzymes appear to have the potential to predict efficacy and/or safety of fluoropyrimidine-based treatment: thymidine phosphorylase (TP), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD). We evaluated the association between baseline TP, TS and DPD and outcome (DFS and OS).


Patients (pts) with stage III colon cancer received either XELOX (8 cycles, 24w) or bolus 5-FU/LV (Mayo Clinic, 6 cycles, 24w; Roswell Park, 4 cycles, 32w). The primary study endpoint was DFS; secondary endpoints included OS. TP, TS and DPD expression levels were determined in formalin-fixed, paraffin-embedded tissues by RT-PCR, and the median used as a cut-off point: high (above median) vs. low (below median).


The biomarker population included 498 (26%) of 1886 pts entered (XELOX, n = 242; 5-FU/LV, n = 256). Baseline demographics, tumour characteristics, cancer history and efficacy (DFS and OS) were similar to those in the main study population. Cox regression analysis for DFS is shown in the table. In the XELOX group pts with low tumour DPD and TP levels and a high TP/DPD ratio appeared to have significantly better DFS; this effect was not observed with 5-FU/LV.

Covariate (high vs. low) HR 95% CI p value HR 95% CI p value
DPD 2.45 1.55–3.86 0.0001 0.69 0.47–1.00 NS
TP 1.73 1.10–2.72 0.0186 0.81 0.55–1.18 NS
TS 0.90 0.58–1.40 NS 0.91 0.62–1.33 NS
TP/DPD ratio 0.54 0.34–0.86 0.0091 0.76 0.51–1.13 NS


These exploratory findings suggest that low tumour levels of DPD may be predictive for XELOX efficacy when given as adjuvant therapy in pts with resected stage III colon cancer. There was no correlation between DPD levels and outcome in the 5-FU/LV group. These data raise the possibility of predictive markers for XELOX but, until validated prospectively, would currently not have a role in treatment decisions.


H. Schmoll: Consultant or Advisory Board: Roche Research Funding: Roche.

J. Tabernero: Consultant or Advisory Board: Roche.

J.A. Maroun: Consultant or Advisory Board: Roche. Honoraria: Roche. Research Funding: Roche.

F. De Braud: Honoraria: Roche.

T. Price: Consultant or Advisory Board: Roche.

E. Van Cutsem: Research Funding: Roche.

M. Hill: Consultant or Advisory Board: Roche. Honoraria: Roche. Research Funding: Roche.

S. Hoersch: Employed by Dr. Manfred Köhler GmbH/Roche.

K. Rittweger: Employed by Hoffmann-La Roche Inc.

D. Haller: Consultant or Advisory Board: Roche. Honoraria: Roche. Research Funding: Roche.