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Correlation of toxicity and efficacy with pharmacokinetics (PK) of pegylated liposomal doxorubicin (PLD) (Caelyx®)

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Abstract

Purpose

Pegylated liposomal doxorubicin (PLD) is used to treat patients with breast and gynecological cancers. In order to optimize treatment with PLD, we assessed the prognostic and predictive factors for efficacy of PLD.

Methods

Seventeen patients treated with PLD 30 or 40 mg/m2 underwent pharmacokinetic sampling during the first cycle of treatment. PLD exposure was calculated. An univariate analysis was performed with the variables: hand–foot syndrome, mucositis, rash, neutropenia, age, tumor type, number of previous therapies, ECOG performance status and progression-free survival (PFS). Candidate variables with p ≤ 0.1 were selected for the multivariate analysis.

Results

Based on the results of the multivariate analysis, the PLD exposure (log AUC) was higher in patients who experienced rash (p = 0.002) and mucositis (p = 0.001) compared to those who did not have these adverse events. The development of hand–foot syndrome was significantly related to a lower risk of disease progression (HR 0.1; 95 % CI 0.02–0.64). Patients with an ECOG status of 0 had a longer PFS than the patients with an ECOG status of 1 (HR 5.4; 95 % CI 1.3–22.8). Moreover, PLD exposure (ln AUC) was also positively related to PFS (HR 0.001; 95 % CI 0.00–0.42).

Conclusions

The extent of the exposure to PLD was correlated with more adverse events and longer PFS. This has important clinical implications, since dose reductions or interruptions might thus negatively affect treatment outcomes. More attention should be paid to preventive and supportive measures of adverse events of PLD to keep the exposure to PLD as high as possible.

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Acknowledgments

This work was supported by the manufacturers of temsirolimus and PLD: Wyeth Pharmaceuticals, Pfizer bv, Schering Plough and Janssen-Cilag bv. These sponsors had no involvement in the study design, in the collection, analysis and interpretation of data, in the writing of the manuscript or in the decision to submit the manuscript for publication. Dr. Ottevanger and Dr. van Herpen have received funding from the manufacturers of temsirolimus and PLD to perform this study.

Conflict of interest

All other authors declare no conflict of interests.

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Authors and Affiliations

  1. Department of Medical Oncology, 452, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands

    Marye J. Boers-Sonderen, Carla M. L. van Herpen, Winette T. A. van der Graaf, Ingrid M. E. Desar, Mirjam G. W. Arens- van der Logt & Petronella B. Ottevanger

  2. Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands

    Yvo M. de Beer

  3. School CAPHRI, Maastricht University, Maastricht, The Netherlands

    Yvo M. de Beer

  4. Department of Toxicology, Maastricht University, Maastricht, The Netherlands

    Yvo M. de Beer

  5. Department of Clinical Pharmacy, Radboud University Medical Centre, Nijmegen, The Netherlands

    Nielka P. van Erp

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  1. Marye J. Boers-Sonderen
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  2. Carla M. L. van Herpen
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  3. Winette T. A. van der Graaf
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  4. Ingrid M. E. Desar
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  7. Petronella B. Ottevanger
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Corresponding author

Correspondence to Marye J. Boers-Sonderen.

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Boers-Sonderen, M.J., van Herpen, C.M.L., van der Graaf, W.T.A. et al. Correlation of toxicity and efficacy with pharmacokinetics (PK) of pegylated liposomal doxorubicin (PLD) (Caelyx®). Cancer Chemother Pharmacol 74, 457–463 (2014). https://doi.org/10.1007/s00280-014-2514-9

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  • DOI: https://doi.org/10.1007/s00280-014-2514-9

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