Risk factors for pegylated liposomal doxorubicin-induced palmar-plantar erythrodysesthesia over time: assessment of monocyte count and baseline clinical parameters

Cancer Chemother Pharmacol. 2015 Nov;76(5):1033-9. doi: 10.1007/s00280-015-2875-8. Epub 2015 Sep 29.


Purpose: Pegylated liposomal doxorubicin (PLD) is widely used in relapsing ovarian carcinoma. Its original formulation is metabolized by the monocyte-macrophage system. One of its main toxicities is the palmoplantar erythrodysesthesia (PPE) syndrome. To date, no predictive factors of PPE have been identified.

Methods: Data of patients (pts) treated with PLD between 2005 and 2014 were retrospectively collected. A case-control study was performed, comparing main baseline clinical and biological characteristics of pts experiencing PPE and those who did not, after at least three cycles of PLD. A pilot analysis of blood monocyte subpopulations (classical, intermediate and non-classical) was performed by FACS in selected pts.

Results: Among 88 pts treated with PLD, 28 experienced PPE of any grade (31, 95 % CI 21-41). The first occurrence of PPE was at first cycle in only 11 % of pts, peaked at cycle 2 (32 %) and represented 57 % of cases after cycle 3. Baseline characteristics of pts with PPE were compared to 27 control pts who received at least 3 cycles. Older pts represented 61 % of pts with PPE and 15 % of pts without PPE (p = 0.04 by Chi-square test). Monocyte count and inflammatory parameters were not associated with PPE. However, the analysis of monocyte subpopulations revealed a large inter-patient variability.

Conclusion: Contrary to most acute toxicities, PPE occurred more frequently after several cycles, suggesting a PLD body accumulation through repeated cycles. PPE was more frequent in pts older than 70 years. Monocyte subpopulations may have different roles on PLD metabolism and warrant further studies.

Keywords: Elderly; Monocytes; Ovarian neoplasm; Palmar-plantar erythrodysesthesia; Pegylated liposomal doxorubicin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carboplatin / administration & dosage
  • Carcinoma / drug therapy*
  • Case-Control Studies
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / therapeutic use
  • Female
  • Hand-Foot Syndrome / etiology*
  • Hematologic Diseases / chemically induced
  • Humans
  • Leukocyte Count
  • Male
  • Middle Aged
  • Monocytes / drug effects*
  • Ovarian Neoplasms / drug therapy*
  • Paclitaxel / administration & dosage
  • Pilot Projects
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / adverse effects*
  • Polyethylene Glycols / therapeutic use
  • Retrospective Studies
  • Sarcoma / drug therapy
  • Stomatitis / chemically induced
  • Thymus Neoplasms / drug therapy
  • Young Adult


  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin
  • Carboplatin
  • Paclitaxel