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Multicentre phase II study using increasing doses of irinotecan combined with a simplified LV5FU2 regimen in metastatic colorectal cancer

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Abstract

Purpose

Irinotecan at 180 mg/m² combined with an infusional 5-fluorouracil/leucovorin (5-FU/LV) regimen (FOLFIRI) is a standard first line therapy for metastatic colorectal cancer (mCRC). This phase II study aimed to assess whether increasing the irinotecan dose in the first line FOLFIRI regimen would benefit mCRC patients.

Patients and methods

Patients received FOLFIRI every 2 weeks for up to six cycles, comprising a 5-FU/LV regimen combined with irinotecan at 180 mg/m² (cycle 1), increasing to 220 mg/m² (cycle 2) and 260 mg/m² (cycle 3 and subsequent cycles) dependent on toxicity. Efficacy and safety were determined in the intention to treat (ITT) population and in patients able to receive irinotecan at 260 mg/m² for at least four cycles [high-dose (HD) population].

Results

Fifty-four eligible patients were included. Among them, 44 (81.5%) formed the HD population. The ITT objective response rate was 48% (90%CI: 36–60) with 25/26 of the responses in the HD population. The disease control rate was 76% (90%CI: 65–85) and median overall survival was 20.4 months (90%CI: 6.4–27.1). The main grade 3/4 toxicities (ITT/HD populations) were neutropenia (61%/59%), and diarrhoea (18%/11%), respectively.

Conclusions

This study confirms the feasibility of increasing the standard dose of the irinotecan component of FOLFIRI to 260 mg/m², for more than 80% of patients but does not support a clear advantage of this strategy on unselected mCRC patients.

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Acknowledgments

This work was supported in part by Regional PHRC (Programme Hospitalier de Recherche Clinique), in part by Laboratoire Chugaï.

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Authors and Affiliations

  1. Digestive Department, CRLC Val d’Aurelle Parc Euromédecine, 34298, Montpellier Cedex 5, France

    Jacqueline Duffour, Patrick Chalbos & Marc Ychou

  2. Biostatistic Unit, CRLC Val d’Aurelle, Montpellier, France

    Sophie Gourgou

  3. Centre Leon Berard, Lyon, France

    Françoise Desseigne

  4. CHR Nîmes, Nimes, France

    Charles Debrigode

  5. Clinique Ste Catherine, Avignon, France

    Laurent Mineur

  6. Onco-Pharmacology Unit, CRLC Val d’Aurelle, Montpellier, France

    Frédéric Pinguet, Sylvain Poujol & Françoise Bressole

Authors
  1. Jacqueline Duffour
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  2. Sophie Gourgou
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  3. Françoise Desseigne
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  4. Charles Debrigode
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  5. Laurent Mineur
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  6. Frédéric Pinguet
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  7. Sylvain Poujol
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  8. Patrick Chalbos
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  9. Françoise Bressole
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  10. Marc Ychou
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Corresponding author

Correspondence to Jacqueline Duffour.

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Duffour, J., Gourgou, S., Desseigne, F. et al. Multicentre phase II study using increasing doses of irinotecan combined with a simplified LV5FU2 regimen in metastatic colorectal cancer. Cancer Chemother Pharmacol 60, 383–389 (2007). https://doi.org/10.1007/s00280-006-0372-9

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  • DOI: https://doi.org/10.1007/s00280-006-0372-9

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