Oral leukoplakia, a precancerous lesion of squamous cell carcinoma, in patients with long-term pegylated liposomal doxorubicin treatment

Medicine (Baltimore). 2018 Feb;97(7):e9932. doi: 10.1097/MD.0000000000009932.

Abstract

Pegylated liposomal doxorubicin (PLD) has a good safety profile, but long-term use has been associated with development of squamous cell carcinoma of the tongue and oral cavity (SCCTO) in some patients. The study objective was to estimate the prevalence of oral leukoplakia, a known precursor of SCCTO, in patients with ovarian cancer and long-term PLD use.After approval of the institutional review board, medical record of 114 patients who were treated with PLD at our institution between January 2010 and December 2016 were retrospectively reviewed. All those patients have been referred for routine monitoring of oral mucositis every time before administration by a dentist. The patient characteristics included in the evaluation were age, smoking and drinking habits, the PLD dose and schedule, and presence or absence of oral leukoplakia and SCCTO at each oral examination. The relationships of the incidence of oral leukoplakia and patient characteristics were analyzed.The median total PLD dose was 160 (range 40-1550) mg/m. Oral leukoplakia was seen in 6 (5.3%) patients. The median PLD dose, at the time of oral leukoplakia diagnosis, was 685 (range 400-800) mg/m. SCCTO was not found. Univariate analysis revealed that age, Brinkman index, and habitual drinking were not considered as risk factors for oral leukoplakia, and only total PLD dose (OR, 1.470; 95% CI, 1.19-1.91; P < .001) remained as a significant independent risk factor for oral leukoplakia. The ROC curve analysis indicated that the optimal cutoff value of the total PLD dose to predict development of oral leukoplakia was 400 mg/m. The sensitivity was 100% and the specificity was 88.8%. No patient discontinued PLD because of oral leukoplakia or SCCTO.The 2 most important clinical observations were the occurrence of oral leukoplakia in patients with long-term PLD use and that the development of oral leukoplakia was related to a total cumulative dose ≥400 mg/m. Routine oral surveillance is recommended, particularly when the cumulative total dose exceeds 400 mg/m.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibiotics, Antineoplastic / adverse effects*
  • Doxorubicin / adverse effects
  • Doxorubicin / analogs & derivatives*
  • Drug Administration Schedule
  • Female
  • Humans
  • Leukoplakia, Oral / chemically induced*
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Polyethylene Glycols / adverse effects
  • Retrospective Studies
  • Risk Factors

Substances

  • Antibiotics, Antineoplastic
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin