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

M.J. Boers-Sonderen, C.M.L. van Herpen, W.T.A. van der Graaf, I.M.E. Desar, M.G.W. Arens-van der Logt, Y.M. de Beer, P.B. Ottevanger, N.P. van Erp

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)

Abstract

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. Seventeen patients treated with PLD 30 or 40 mg/m(2) 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 a parts per thousand currency sign 0.1 were selected for the multivariate analysis. 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). 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.
Original languageEnglish
Pages (from-to)457-463
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume74
Issue number3
DOIs
Publication statusPublished - Sep 2014

Keywords

  • Pegylated liposomal doxorubicin
  • Pharmacokinetics
  • Pharmacodynamics
  • Progression-free survival
  • Toxicities
  • PERFORMANCE LIQUID-CHROMATOGRAPHY
  • ADVANCED BREAST-CANCER
  • RANDOMIZED PHASE-III
  • POLYETHYLENE-GLYCOL
  • KAPOSIS-SARCOMA
  • TRIAL
  • CARCINOMA
  • RECURRENT
  • PACLITAXEL
  • TOPOTECAN

Cite this

Boers-Sonderen, M. J., van Herpen, C. M. L., van der Graaf, W. T. A., Desar, I. M. E., Arens-van der Logt, M. G. W., de Beer, Y. M., Ottevanger, P. B., & van Erp, N. P. (2014). Correlation of toxicity and efficacy with pharmacokinetics (PK) of pegylated liposomal doxorubicin (PLD) (Caelyx(A (R))). Cancer Chemotherapy and Pharmacology, 74(3), 457-463. https://doi.org/10.1007/s00280-014-2514-9