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Chemotherapy-induced neutropenia: a useful predictor of treatment efficacy?

Nature Clinical Practice Oncology volume 3, pages 114–115 (2006)Cite this article

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Ten years ago, Howard Gurney wrote a seminal paper on the pitfalls of the body surface area (BSA)-based dose calculation method in oncology.1 A poor correlation between BSA and pharmacokinetic parameters of most cytotoxic agents was demonstrated, highlighting the substantial inaccuracy of the BSA-based system. High inter-patient variability and the criteria used for identifying recommended doses in Phase I trials mean that only some patients attain the correct blood level of the drug, even when the dose is administered at the same concentration per square meter of BSA. Some patients will attain blood levels of the drug that are too high, increasing the likelihood of severe toxicity, but an even higher proportion of patients will receive doses that are too low.2 The latter patients would apparently have a satisfying clinical course because of the absence of toxicity, but, in fact, they are at concrete risk of reduced efficacy.3

Despite the importance of Gurney's message, the dosing system of cytotoxic drugs in the new millennium remains the same. Interest in using toxicity as a surrogate marker for treatment activity has increased as evidence has become available for a link between toxicity and efficacy of some of the new target-based anticancer agents (e.g. skin toxicity for erlotinib and cetuximab), but much less attention has been paid to this correlation within traditional chemotherapy. Although a publication bias could have masked negative findings on this topic, the few papers that are available have consistently shown a better outcome for patients who experience the effect that is chosen as a surrogate marker of treatment activity (normally hematologic toxicity). Several studies have been conducted in breast cancer patients receiving adjuvant chemotherapy.4,5,6 Those studies found a better outcome for patients experiencing greater toxicity (e.g. leukocyte nadir, or any hematologic toxicity) during treatment.

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Authors and Affiliations

  1. works in the Clinical Trials Unit of the National Cancer Institute of Naples, Naples

    Massimo Di Maio

  2. Chief of the Division of Medical Oncology and Director of the Department of Oncology/Hematology at the 'SG Moscati' Hospital, Avellino

    Cesare Gridelli

  3. Professor of Medical Statistics at the Second University of Naples and Head of the Department of Health Statistics of the University Hospital, Naples

    Ciro Gallo

  4. Director of the Clinical Trials Unit at the National Cancer Institute of Naples, Naples, Italy

    Francesco Perrone

Authors
  1. Massimo Di Maio
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  2. Cesare Gridelli
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  3. Ciro Gallo
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  4. Francesco Perrone
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Corresponding author

Correspondence to Francesco Perrone.

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The authors declare no competing financial interests.

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Di Maio, M., Gridelli, C., Gallo, C. et al. Chemotherapy-induced neutropenia: a useful predictor of treatment efficacy?. Nat Rev Clin Oncol 3, 114–115 (2006). https://doi.org/10.1038/ncponc0445

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