Bifractionated CPT-11 with LV5FU2 infusion (FOLFIRI-3) in combination with bevacizumab: clinical outcomes in first-line metastatic colorectal cancers according to plasma angiopoietin-2 levels. - Archive ouverte HAL Access content directly
Journal Articles BMC Cancer Year : 2013

Bifractionated CPT-11 with LV5FU2 infusion (FOLFIRI-3) in combination with bevacizumab: clinical outcomes in first-line metastatic colorectal cancers according to plasma angiopoietin-2 levels.

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Stefano Kim
  • Function : Author
  • PersonId : 950310
Erion Dobi
  • Function : Author
  • PersonId : 941153
Marine Jary
  • Function : Author
  • PersonId : 1220126
  • IdHAL : marine-jary
Elsa Curtit
  • Function : Author
  • PersonId : 941149
Bruno Heyd
  • Function : Author
  • PersonId : 950314
Serge Fratte
  • Function : Author
  • PersonId : 950315
Denis Cléau
  • Function : Author
  • PersonId : 950316
Najib Lamfichekh
  • Function : Author
  • PersonId : 950317
Boris Guiu
  • Function : Author
  • PersonId : 950319

Abstract

BACKGROUND: Optimization of chemotherapy effectiveness in metastatic colorectal cancers (mCRC) is a major endpoint to enhance the possibility of curative intent surgery. FOLFIRI3 has shown promising results as second-line chemotherapy for mCRC patients previously exposed to oxaliplatin. The clinical efficacy of FOLFIRI3 was never determined in association with bevacizumab in non-previously treated mCRC patients. METHODS: We conducted a phase II clinical trial to characterize the response rate and toxicity profile of FOLFIRI3-bevacizumab as initial treatment for mCRC. Sixty-one patients enrolled in 3 investigation centers were treated with FOLFIRI3-bevacizumab (median of 10 cycles) followed by a maintenance therapy combining bevacizumab and capecitabine. Levels of plasma angiopoietin-2 (Ang-2) were measured by enzyme-linked immunosorbent assay at baseline. RESULTS: Overall response rate (ORR) was 66.7% (8% of complete and 58% of partial responses). The disease control rate was 91.7%. After a median time of follow-up of 46.7 months, 56 patients (92%) had progressed or died. The median progression free survival (PFS) was 12.7 months (95% confidence interval (CI) 9.7-15.8 months). The median overall survival (OS) was 24.5 months (95% CI: 10.6-38.3 months). Twenty-one patients underwent curative intent-surgery including 4 patients with disease initially classified as unresectable. Most common grade III-IV toxicities were diarrhea (15%), neutropenia (13%), asthenia (10%), and infections (4%). Hypertension-related medications needed to be increased in 3 patients. In multivariate analysis, surgery of metastases and Ang-2 levels were the only independent prognostic factors for PFS and OS. Indeed, baseline level of Ang-2 above 5 ng/mL was confirmed as an independent prognostic factor for progression free survival (HR = 0.357; 95% CI: 0.168-0.76, p = 0.005) and overall survival (HR = 0.226; 95% CI: 0.098-0.53, p = 0.0002). CONCLUSIONS: As front-line therapy, FOLFIRI-3-bevacizumab is associated with an acceptable toxicity and induced promising objective response rates. However, unfavorable clinical outcomes were observed in patients with high levels of angiopoietin-2.
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inserm-00922823 , version 1 (30-12-2013)

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Stefano Kim, Erion Dobi, Marine Jary, Franck Monnien, Elsa Curtit, et al.. Bifractionated CPT-11 with LV5FU2 infusion (FOLFIRI-3) in combination with bevacizumab: clinical outcomes in first-line metastatic colorectal cancers according to plasma angiopoietin-2 levels.. BMC Cancer, 2013, 13 (1), pp.611. ⟨10.1186/1471-2407-13-611⟩. ⟨inserm-00922823⟩

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