Symptomatic mucocutaneous toxicity of hydroxyurea in Philadelphia chromosome-negative myeloproliferative neoplasms the mister hyde face of a safe drug

Roberto Latagliata, Antonio Spadea, Michele Cedrone, Jonny Di Giandomenico, Marianna De Muro, Nicoletta Villivà, Massimo Breccia, Barbara Anaclerico, Raffaele Porrini, Francesca Spirito, Angela Rago, Giuseppe Avvisati, Giuliana Alimena, Marco Montanaro, Alessandro Andriani, Paola Volpicelli, Antonietta Ferretti, Maria Gabriella Mazzucconi, Luciana Annino, Stefano FeliciEnrico Montefusco, Ignazio Majolino, Giulio Trapè, Gloria Pessina, Ettore Cotroneo, Francesco Lo-Coco, Elisabetta Abruzzese, Giuseppe Cimino

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)404-409
Number of pages6
JournalCancer
Volume118
Issue number2
DOIs
Publication statusPublished - Jan 15 2012

Keywords

  • Hydroxyurea
  • Mucocutaneous toxicity
  • Myeloproliferative neoplasms
  • Partial resolution

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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