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Individual Fluorouracil Dose Adjustment in FOLFOX Based on Pharmacokinetic Follow-Up Compared With Conventional Body-Area-Surface Dosing: A Phase II, Proof-of-Concept Study

  • Olivier Capitain
    Affiliations
    Oncopharmacology — Pharmacogenetics Department CRCNA INSERM U892, Institut de Cancérologie de l'Ouest, 49933 Angers Cedex, France

    Department of Medical Oncology and Clinical Pharmacology, Institut de Cancérologie de l'Ouest, 49933 Angers Cedex, France
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  • Andreaa Asevoaia
    Affiliations
    Oncopharmacology — Pharmacogenetics Department CRCNA INSERM U892, Institut de Cancérologie de l'Ouest, 49933 Angers Cedex, France
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  • Michele Boisdron-Celle
    Correspondence
    Address for correspondence: Michele Boisdron-Celle, PharmD, Centre Régional de Lutte Contre le Cancer Paul Papin, 49933 Angers Cedex, France
    Affiliations
    Oncopharmacology — Pharmacogenetics Department CRCNA INSERM U892, Institut de Cancérologie de l'Ouest, 49933 Angers Cedex, France
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  • Anne-Lise Poirier
    Affiliations
    Department of Statistics and Data Management, Institut de Cancérologie de l’Ouest, Angers Cedex, France
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  • Alain Morel
    Affiliations
    Oncopharmacology — Pharmacogenetics Department CRCNA INSERM U892, Institut de Cancérologie de l'Ouest, 49933 Angers Cedex, France
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  • Erick Gamelin
    Affiliations
    Oncopharmacology — Pharmacogenetics Department CRCNA INSERM U892, Institut de Cancérologie de l'Ouest, 49933 Angers Cedex, France

    Department of Medical Oncology and Clinical Pharmacology, Institut de Cancérologie de l'Ouest, 49933 Angers Cedex, France
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      Abstract

      Background

      To compare the efficacy and safety of pharmacokinetically (PK) guided fluorouracil (5-FU) dose adjustment vs. standard body-surface-area (BSA) dosing in a FOLFOX (folinic acid, fluorouracil, oxaliplatin) regimen in metastatic colorectal cancer (mCRC).

      Patients And Methods

      A total of 118 patients with mCRC were administered individually determined PK-adjusted 5-FU in first-line FOLFOX chemotherapy. The comparison arm consisted of 39 patients, and these patients were also treated with FOLFOX with 5-FU by BSA. For the PK-adjusted arm 5-FU was monitored during infusion, and the dose for the next cycle was based on a dose-adjustment chart to achieve a therapeutic area under curve range (5-FUODPM Protocol).

      Results

      The objective response rate was 69.7% in the PK-adjusted arm, and median overall survival and median progression-free survival were 28 and 16 months, respectively. In the traditional patients who received BSA dosage, objective response rate was 46%, and overall survival and progression-free survival were 22 and 10 months, respectively. Grade 3/4 toxicity was 1.7% for diarrhea, 0.8% for mucositis, and 18% for neutropenia in the dose-monitored group; they were 12%, 15%, and 25%, respectively, in the BSA group.

      Conclusions

      Efficacy and tolerability of PK-adjusted FOLFOX dosing was much higher than traditional BSA dosing in agreement with previous reports for 5-FU monotherapy PK-adjusted dosing. Analysis of these results suggests that PK-guided 5-FU therapy offers added value to combination therapy for mCRC.

      Keywords

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