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Medline ® Abstract for Reference 81

of 'Cutaneous side effects of conventional chemotherapy agents'

Palmar-plantar erythrodysesthesia syndrome following treatment with high-dose methotrexate or high-dose cytarabine.
Karol SE, Yang W, Smith C, Cheng C, Stewart CF, Baker SD, Sandlund JT, Rubnitz JE, Bishop MW, Pappo AS, Jeha S, Pui CH, Relling MV
Cancer. 2017;123(18):3602. Epub 2017 May 11.
BACKGROUND: Palmar-plantar erythrodysesthesia syndrome (PPES) is an uncommon side effect of high-dose cytarabine or methotrexate. Prior case reports of PPES have been limited, and the predisposing factors for the development of PPES remain unknown.
METHODS: A review of databases identified 22 patients (1.3%) who developed 39 episodes of PPES among 1720 patients after treatment with high-dose cytarabine or methotrexate.
RESULTS: Symptoms lasted a mean of 6.4 days. Hands and feet were both involved in 68% of the initial episodes. Parenteral opioids were required for pain control by 27% of the patients. In comparison with the 1698 children treated with similar therapy, the children who developed PPES were older (mean age at diagnosis, 14.3 vs 7.7 years; P = 7.5×10(-7) ). The frequency of PPES was less common in patients receiving methotrexate alone (7 of 946 or 0.7%) versus cytarabine (7 of 205 or 3.4%; P = .005) but was not different for those receiving both high-dose methotrexate and cytarabine (8 of 569 or 1.4%; P = .32). Prolonged infusions of methotrexate were associated with less frequent PPES in comparison with rapid infusions (P = 1.5×10(-5) ), as was the co-administration of dexamethasone with cytarabine (P = 2.5×10(-6) ). Self-described race and sex were not associated with PPES. In a multivariate analysis, older age and high-dose cytarabine administration without dexamethasone remained associated with PPES (P = 1.1×10(-4) and P = .038, respectively). A genome-wide association study did not identify any associations with PPES meeting the genome-wide significance threshold, but top variants were enriched for skin expression quantitative trait loci, including rs11764092 in AUTS2 (P = 6.45×10(-5) ).
CONCLUSIONS: These data provide new insight into the incidence of PPES as well as its risk factors. Cancer 2017;123:3602-8.©2017 American Cancer Society.
Comprehensive Cancer Center, St. Jude Children's Research Hospital, Memphis, Tennessee.