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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KRAS and NRAS mutations are usually present in the majority of neoplastic cells, whereas BRAF and PIK3CA mutations often affect a limited fraction of transformed cells. Resistance to cetuximab in low-KRAS patients might be driven by the complex mutational profile rather than KRAS mutation load.

This study demonstrates that NGS analysis in mCRC is feasible, reveals high level of intra and intertumor heterogeneity, and identifies patients that might benefit of FOLFIRI plus cetuximab treatment.

This study indicates that RAS testing of liquid biopsy results in a similar outcome when compared with tissue testing in mCRC patients receiving first-line anti-EGFR monoclonal antibodies.