title: Symptomatic mucocutaneous toxicity of hydroxyurea in Philadelphia chromosome-negative myeloproliferative neoplasms: the Mister Hyde face of a safe drug.
abstract: BACKGROUND
  The current study was conducted to evaluate severe mucocutaneous toxicity during treatment with hydroxyurea (HU) in a large cohort of patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPN).
  
  
  METHODS
  Among 993 consecutive patients newly diagnosed with MPN at 4 centers in Rome between January 1980 and December 2009, 614 patients (277 men and 337 women with a median age of 64.4 years [interquartile range (IR), 54.4 years-72.7 years]) received HU. HU was administered as first-line treatment in 523 patients (85.2%) and as ≥ second-line treatment in 91 patients (14.8%).
  
  
  RESULTS
  Mucocutaneous toxicity was reported in 51 patients (8.3%) after a median period from the initiation of HU treatment of 32.1 months (IR, 10.5 months-74.6 months) and a mean HU dose of 1085 mg (± 390 mg); 30 patients (58.8%) developed a painful ulcerative skin toxicity, mainly located in the perimalleolar area; 11 patients (21.6%) had oral aphthous ulcers; and 10 patients (19.6%) developed a nonulcerative skin toxicity with erythema and skin infiltration. After the mucocutaneous toxicity occurred, HU treatment was continued at the same dose in 5 patients (9.8%), reduced in 12 patients (23.5%), and temporarily discontinued in 7 patients (13.7%); the remaining 27 patients (52.9%) required a permanent drug discontinuation. After a median period of 4.3 months (IR, 2.4 months-9.0 months) from the onset of the skin toxicity, 39 patients (76.5%) had a complete resolution and 12 patients (23.5%) had improvement without complete resolution.
  
  
  CONCLUSIONS
  Mucocutaneous toxicity during HU treatment is more common than expected and may present with different clinical features. Moreover, it often requires a permanent drug discontinuation and only a partial resolution is reported to occur in approximately 25% of patients.
authors.affiliation: Department of Cellular Biotechnologies and Hematology, La Sapienza University, Rome, Italy. rob.lati@libero.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Latagliata
authors.forename: Antonio
authors.initials: A
authors.lastname: Spadea
authors.forename: Michele
authors.initials: M
authors.lastname: Cedrone
authors.forename: Jonny
authors.initials: J
authors.lastname: Di Giandomenico
authors.forename: Marianna
authors.initials: M
authors.lastname: De Muro
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Villivà
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
authors.forename: Barbara
authors.initials: B
authors.lastname: Anaclerico
authors.forename: Raffaele
authors.initials: R
authors.lastname: Porrini
authors.forename: Francesca
authors.initials: F
authors.lastname: Spirito
authors.forename: Angela
authors.initials: A
authors.lastname: Rago
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Avvisati
authors.forename: Giuliana
authors.initials: G
authors.lastname: Alimena
authors.forename: Marco
authors.initials: M
authors.lastname: Montanaro
authors.forename: Alessandro
authors.initials: A
authors.lastname: Andriani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000188:drug therapy*; D010677:Philadelphia Chromosome; D012871:Skin Diseases / Q000139:chemically induced*; D012883:Skin Ulcer / Q000139:chemically induced; D028761:Withholding Treatment
chemical_list: D000970:Antineoplastic Agents; D006918:Hydroxyurea