Letter
Phase II study of oral miltefosine in patients with squamous cell head and neck cancer

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    Hexadecylphosphocholine (HePC) represents a lead compound from the group of alkyphosphocholines [34] which is approved for a topical treatment of metastasized breast cancer [35,36]. Preclinically, HePC showed a promising anti-cancer activity on many tumor cell lines in-vitro as well as in animal tumor models in vivo [37,38] but failed later to progress in clinical studies on patients due to a dose-limiting gastrointestinal toxicity following the oral administration [39–41]. Parenteral application of the drug is not possible since HePC has hemolytic effects on blood cells [42].

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  • In vitro effects of the antitumor drug miltefosine on human erythrocytes and molecular models of its membrane

    2019, Biochimica et Biophysica Acta - Biomembranes
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    Moreover, it is effective against various tumor cells, including soft tissue sarcomas, metastatic colorectal cancer, head and neck squamous cell carcinoma, hematological malignancies, and brain tumors [7,8]; besides, it has been proven to be effective in the treatment of infections with fungi, bacteria and parasites [7,9,10]. However, miltefosine exhibits toxicity in the epithelial cells of the gastrointestinal tract when the administration is oral, and it was found to be highly hemolytic when it is parenterally administered [11,12]. These severe side effects limited its maximum-tolerated daily dose, preventing antiproliferative effects in vivo and its use as a systemic agent [13].

  • Inhibition of Akt and other AGC kinases: A target for clinical cancer therapy?

    2018, Seminars in Cancer Biology
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    It can be incorporated into cell membranes and inhibits the membrane-linked protein kinase C (PKC) as well as Akt signaling [8,9]. Miltefosine was evaluated in patients with soft tissue sarcomas [10], colorectal cancer [11] and squamous cell carcinoma of the head and neck [12]. Unfortunately, the dose required for an anti-tumor effect was above the maximum tolerated dose (MTD) and thus this drug was not developed as a systemic anti-cancer drug.

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