Pemetrexed-Induced Rash May Be Prevented by Supplementary Corticosteroids

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  • Sakurada Takumi
    Department of Pharmacy, Tokushima University Hospital
  • Kakiuchi Soji
    Department of Medical Oncology, Institute of Biomedical Sciences, The University of Tokushima Graduate School Department of Respiratory Medicine and Rheumatology, Institute of Biomedical Sciences, The University of Tokushima Graduate School
  • Tajima Soichiro
    Department of Pharmacy, Kyushu University Hospital
  • Horinouchi Yuya
    Department of Pharmacy, Tokushima University Hospital
  • Konaka Ken
    Department of Pharmacy, Tokushima University Hospital
  • Okada Naoto
    Department of Pharmacy, Tokushima University Hospital
  • Nishisako Hirotaka
    Department of Pharmacy, Tokushima University Hospital
  • Nakamura Toshimi
    Department of Pharmacy, Tokushima University Hospital
  • Teraoka Kazuhiko
    Department of Pharmacy, Tokushima University Hospital
  • Kawazoe Kazuyoshi
    Department of Pharmacy, Tokushima University Hospital Department of Clinical Pharmacy, Institute of Biomedical Sciences, The University of Tokushima Graduate School
  • Yanagawa Hiroaki
    Clinical Trial Center for Developmental Therapeutics, Tokushima University Hospital
  • Nishioka Yasuhiko
    Department of Respiratory Medicine and Rheumatology, Institute of Biomedical Sciences, The University of Tokushima Graduate School
  • Ishizawa Keisuke
    Department of Pharmacy, Tokushima University Hospital Department of Clinical Pharmacy, Institute of Biomedical Sciences, The University of Tokushima Graduate School

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Pemetrexed, a chemotherapeutic drug, is highly active in non-small cell lung cancer and malignant pleural mesothelioma. Unfortunately, rashes are more commonly associated with pemetrexed than other chemotherapies, and it is recommended that patients receive corticosteroids (8 mg/d of dexamethasone) for 3 d, including the day of pemetrexed administration (day 1). However, the efficacy of corticosteroids in this context has not been fully verified. In this retrospective study, we evaluated the medical records of 78 patients who received pemetrexed between April 2009 and March 2014, to confirm whether supplementary corticosteroids prevented rash development. The incidence of rash was lower in the 47 patients who received supplementary corticosteroids (after day 1) compared with the incidence among the 31 patients who did not receive supplementary corticosteroids (19.1% vs. 38.7%). The average cutoff dosage of supplementary corticosteroids on day 2 and day 3 was 1.5 mg/d of dexamethasone, as calculated using the receiver operating characteristic curve, and the odds ratio was 0.33 (95% confidence interval: 0.12–0.94). Administration of ≥1.5 mg of corticosteroids on day 2 and day 3 significantly reduced the severity of the rash compared to no supplementary treatment (grades 2/3, 13.3% vs. 33.3%, p<0.05). However, increasing the dose of corticosteroids had no additional effect on rash development. These results suggest that ≥1.5 mg of supplementary dexamethasone on day 2 and day 3 (in addition to day 1) may be necessary for preventing pemetrexed-induced rash, but high doses of dexamethasone (e.g., 8 mg/d) are unnecessary.

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