title: Risk factors for pegylated liposomal doxorubicin-induced palmar-plantar erythrodysesthesia over time: assessment of monocyte count and baseline clinical parameters.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medical Oncology Department, CAncer PErsonalized Medicine, Cochin - Port Royal Hospital, Sorbonne Paris Cité University, Paris, France.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Ajgal
authors.affiliation: Haematology Department, CAncer PErsonalized Medicine, Cochin - Port Royal Hospital, Sorbonne Paris Cité University, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chapuis
authors.affiliation: Medical Oncology Department, CAncer PErsonalized Medicine, Cochin - Port Royal Hospital, Sorbonne Paris Cité University, Paris, France.|Medical Oncology Department, Beaujon Hospital, Clichy, France.
authors.forename: George
authors.initials: G
authors.lastname: Emile
authors.affiliation: Medical Oncology Department, CAncer PErsonalized Medicine, Cochin - Port Royal Hospital, Sorbonne Paris Cité University, Paris, France.
authors.forename: Anatole
authors.initials: A
authors.lastname: Cessot
authors.affiliation: Medical Oncology Department, CAncer PErsonalized Medicine, Cochin - Port Royal Hospital, Sorbonne Paris Cité University, Paris, France.
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Tigaud
authors.affiliation: Medical Oncology Department, CAncer PErsonalized Medicine, Cochin - Port Royal Hospital, Sorbonne Paris Cité University, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Huillard
authors.affiliation: Medical Oncology Department, CAncer PErsonalized Medicine, Cochin - Port Royal Hospital, Sorbonne Paris Cité University, Paris, France.
authors.forename: Pascaline
authors.initials: P
authors.lastname: Boudou-Rouquette
authors.affiliation: Haematology Department, CAncer PErsonalized Medicine, Cochin - Port Royal Hospital, Sorbonne Paris Cité University, Paris, France.
authors.forename: Michaela
authors.initials: M
authors.lastname: Fontenay
authors.affiliation: Medical Oncology Department, CAncer PErsonalized Medicine, Cochin - Port Royal Hospital, Sorbonne Paris Cité University, Paris, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Goldwasser
authors.affiliation: Medical Oncology Department, CAncer PErsonalized Medicine, Cochin - Port Royal Hospital, Sorbonne Paris Cité University, Paris, France. jerome.alexandre@cch.aphp.fr.
authors.forename: Jerome
authors.initials: J
authors.lastname: Alexandre
mesh_terms: D000328:Adult; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D002277:Carcinoma / Q000188:drug therapy*; D016022:Case-Control Studies; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D060831:Hand-Foot Syndrome / Q000209:etiology*; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D012509:Sarcoma / Q000188:drug therapy; D013280:Stomatitis / Q000139:chemically induced; D013953:Thymus Neoplasms / Q000188:drug therapy; D055815:Young Adult
chemical_list: C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D016190:Carboplatin; D017239:Paclitaxel
keywords: Elderly; Monocytes; Ovarian neoplasm; Palmar-plantar erythrodysesthesia; Pegylated liposomal doxorubicin