Open Access Highly Accessed Research article

XELIRI-bevacizumab versus FOLFIRI-bevacizumab as first-line treatment in patients with metastatic colorectal cancer: a Hellenic Cooperative Oncology Group phase III trial with collateral biomarker analysis

Dimitrios Pectasides1*, George Papaxoinis1, Konstantine T Kalogeras23, Anastasia G Eleftheraki4, Ioannis Xanthakis2, Thomas Makatsoris5, Epaminondas Samantas6, Ioannis Varthalitis7, Pavlos Papakostas8, Nikitas Nikitas9, Christos N Papandreou10, George Pentheroudakis11, Eleni Timotheadou2, Angelos Koutras5, Joseph Sgouros6, Dimitrios Bafaloukos12, George Klouvas13, Theofanis Economopoulos14, Konstantinos N Syrigos15 and George Fountzilas2

Author Affiliations

1 Oncology Section, Second Department of Internal Medicine, “Hippokration” Hospital, University of Athens School of Medicine, Athens, Greece

2 Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece

3 Translational Research Section, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece

4 Section of Biostatistics, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece

5 Division of Oncology, Department of Medicine, University Hospital of Patras, Rion, Greece

6 Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece

7 Oncology Department, General Hospital of Chania, Creta, Greece

8 Department of Medical Oncology, Hippokration Hospital, Athens, Greece

9 Department of Clinical Therapeutics, Alexandra Hospital, University of Athens School of Medicine, Athens, Greece

10 Department of Internal Medicine, Oncology Section, Larissa University Hospital, Larissa, Greece

11 Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece

12 First Department of Medical Oncology, Metropolitan Hospital, Athens, Greece

13 Second Department of Medical Oncology, Metropolitan Hospital, Athens, Greece

14 Second Department of Internal Medicine, Propaedeutic, Oncology Section, Attikon University Hospital, Athens, Greece

15 Oncology Unit, Third Department of Medicine, Athens Medical School, Sotiria General Hospital, Athens, Greece

For all author emails, please log on.

BMC Cancer 2012, 12:271  doi:10.1186/1471-2407-12-271

Published: 29 June 2012

Abstract

Background

The aim was to compare two standard chemotherapy regimens combined with bevacizumab as first-line treatment in patients with metastatic colorectal cancer.

Methods

Patients previously untreated for metastatic disease were randomized in: group A (irinotecan, capecitabine, bevacizumab, every 3 weeks; XELIRI-bevacizumab) and group B (irinotecan, leucovorin, fluorouracil, bevacizumab, every 2 weeks; FOLFIRI-bevacizumab). Primary endpoint was progression-free survival (PFS). Plasma concentrations of nitric oxide, osteopontin, TGF-β1 and VEGF-A were measured at baseline and during treatment.

Results

Among 285 eligible patients, 143 were randomized to group A and 142 to group B. Fifty-five patients (38.5%) in group A and 57 (40.1%) in group B responded (p = 0.81). After a median follow-up of 42 months, median PFS was 10.2 and 10.8 months (p = 0.74), while median OS was 20.0 and 25.3 months (p = 0.099), for groups A and B, respectively. Most frequent grade 3–4 toxicities (group A vs group B) were neutropenia (13% vs 22%, p = 0.053) and diarrhea (19% vs 11%, p = 0.082). Baseline plasma osteopontin concentrations demonstrated prognostic significance for both PFS and OS.

Conclusions

This trial did not show significant differences in efficacy between the groups. However, the toxicity profile was different. Baseline plasma osteopontin concentrations demonstrated independent prognostic significance. (Registration number: ACTRN12610000270011)

Keywords:
Angiogenic markers; Bevacizumab; Capecitabine; Chemotherapy; Colorectal cancer; Irinotecan