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Model-Based Approach to Early Predict Prolonged High Grade Neutropenia in Carboplatin-Treated Patients and Guide G-CSF Prophylactic Treatment

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Abstract

Purpose

Neutropenia is a major dose-limiting side effect of chemotherapy and is closely related to febrile neutropenia which mainly occurs during the first cycle. Our objectives were to establish model-based decision rules from early absolute neutrophil counts (ANC) to anticipate prolonged high grade neutropenia at cycle 1 and to prevent it through delayed granulocyte colony stimulating factor (G-CSF) administration in carboplatin-treated patients.

Methods

The decision rules were built from Monte Carlo simulations performed with a previously published semi-mechanistic model describing ANC time-course in carboplatin-treated patients with or without concomitant G-CSF therapy.

Results

ANC measured at day 0 (D0, baseline), D4 and D5 were good predictors of prolonged high grade neutropenia at cycle 1. Pegfilgrastim administration on D5 was as effective as the conventional pegfilgrastim administration on D1 but none avoided prolonged high grade neutropenia in all patients. Additional decision rules were thus derived, using the same ANC combination, to identify patients for whom G-CSF was beneficial. All decision rules showed good performances (sensitivity/specificity).

Conclusion

We propose an innovative approach to guide oncologist in their clinical practice. The next step is to perform prospective studies to implement, validate and possibly refine the proposed decision rules.

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Abbreviations

ANC:

Absolute neutrophils counts

G-CSF:

Granulocyte colony-stimulating factor

ROC:

Receiver-operating characteristic

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ACKNOWLEDGMENTS AND DISCLOSURES

We have no competing interest to declare.

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Authors and Affiliations

  1. INRA/ENVT, UMR1331, Toxalim, 31027, Toulouse, France

    Mélanie L. Pastor, Céline M. Laffont & Didier Concordet

  2. INP, Ecole Nationale Vétérinaire de Toulouse, Université de Toulouse, 23, chemin des capelles, BP 87614, 31076, Toulouse, France

    Mélanie L. Pastor

  3. Institut Claudius-Regaud, EA4553, IUCT-Oncopole, Université de Toulouse, 1 avenue Irène Joliot-Curie, 31059, Toulouse, France

    Laurence Gladieff & Etienne Chatelut

Authors
  1. Mélanie L. Pastor
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  2. Céline M. Laffont
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  3. Laurence Gladieff
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  4. Etienne Chatelut
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  5. Didier Concordet
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Correspondence to Mélanie L. Pastor.

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Pastor, M.L., Laffont, C.M., Gladieff, L. et al. Model-Based Approach to Early Predict Prolonged High Grade Neutropenia in Carboplatin-Treated Patients and Guide G-CSF Prophylactic Treatment. Pharm Res 32, 654–664 (2015). https://doi.org/10.1007/s11095-014-1493-1

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  • DOI: https://doi.org/10.1007/s11095-014-1493-1

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