Palmar-plantar erythrodysesthesia (PPE), also called hand-foot syndrome or hand-to-foot syndrome, is a distinctive and relatively frequent dermatologic toxic reaction associated with certain chemotherapeutic agents. Pegylated liposomal doxorubicin (PLD), a long-circulating formulation of doxorubicin in which doxorubicin hydrochloride is encapsulated within pegylated liposomes, is approved to treat patients with metastatic breast cancer, advanced ovarian cancer, and acquired immunodeficiency syndrome-related Kaposi's sarcoma. The incidence of PPE is increased in patients receiving PLD compared with conventional doxorubicin. In studies that utilized the currently approved dose of PLD (50 mg/m(2) every 4 weeks), approximately 50% of all patients receiving PLD experienced PPE, and approximately 20% experienced grade 3 PPE. The pathophysiology of PPE, as it occurs with any drug with which it is associated, is not well understood. Studies evaluating the development of PPE specifically associated with PLD have not fully elucidated the mechanism; however, data support the roles of drug excretion in sweat and local pressure as contributors. When PPE develops, clinical interventions with respect to altering PLD administration include dose reduction, less frequent dosing, and ultimately, drug withdrawal with several consequences on treatment efficacy. This article will review the available data regarding the etiology and potential management strategies of PPE associated with PLD.

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IntroductionRecurrence of endometrial cancer is an important clinical challenge, with median survival rarely exceeding 12 months. The aim of this study was to analyze patterns of endometrial cancer recurrence and associations of these patterns with clinical outcome.MethodsThe study included patients with endometrial cancer who underwent primary surgical treatment with or without adjuvant treatment between July 2004 and June 2017 at the Gynaecologic Oncology Unit of one of three tertiary hospitals of the Catholic University Network in Italy with complete follow-up data available. Information on the date and pattern of recurrence was retrieved for each relapse. Post-relapse survival was recorded as the time from the date of recurrence to the date of death or last follow-up. Survival probabilities were compared using log rank tests, and associations of clinico-pathological characteristics with post-relapse survival were tested using Cox’s regression models.ResultsA total of 1503 patients were included in the analysis. We identified 210 recurrences (14.0%) and 105 deaths (7.0%) at a median follow-up of 34 months (range 1–162). One hundred and fifty-eight recurrences (78.1%) occurred during the first two years of follow-up. Most recurrences were multifocal (n=121, 57.6%) and involved extrapelvic sites (n=38, 65.7%). Parameters associated with post-relapse survival in the univariate analysis included histotype, grade, time to recurrence, pattern of recurrence, number of relapsing lesions, and secondary radical surgery. Only the pattern of recurrence and secondary radical surgery were independent predictors of post-relapse survival in the multivariate analysis (p=0.025 and p=0.0001, respectively).ConclusionLymph node recurrence and the feasibility of secondary radical surgery were independent predictors of post-relapse survival in patients with recurrent endometrial cancer.

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