A clinical phase I trial with an oral formulation of miltefosine (MIL) was performed in patients with various advanced malignant diseases. The capsulated drug (50 mg or 100 mg capsules) was given once a week over a period of twelve hours with a starting dose of 100 mg (2x50 mg). Dose escalation proceeded up to 300 mg per week. At least three patients were treated at each dose level for eight weeks or until progressive disease or dose limiting toxicity occurred. 34 patients entered this study with 26 patients completing one eight-week course of therapy. Only gastrointestinal side effects were seen, namely nausea and vomiting or diarrhea up to grade III (WHO). Severity of these side effects was dose-related, but there was considerable individual variation. MTD was reached at the 300 mg dose level. Pharmacokinetic studies performed at this dose level showed peak plasma levels of approx. 15 nmol/ml and a plasma half life in excess of eight days after application on one single day. No objective remission has been seen in the patients of this study.
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A clinical phase II trial with an oral formulation of miltefosine (MIL) was performed in patients with non-small cell lung cancer (NSCLC). Eligibility criteria for this phase II study included histological proof of NSCLC, measurable locally advanced or metastatic disease without previous radiotherapy of the indicator lesions, no chemotherapy for the diagnosis of cancer prior to entry into the study, WHO performance status of grade < 2, and informed consent. The capsulated drug was given twice daily at a single dose of 50 mg for the first week with the option of increasing the daily dose to 150 mg (50 mg×3) in the second week if tolerability was good. The minimum intended treatment duration was 9 weeks. Twenty-six patients have been entered into the study and 25 are evaluable for toxicity (WHO criteria). Twenty-one patients are evaluable for toxicity and response (WHO criteria). There was 1 PR and 3 patients had a NC of their disease with a duration exceeding twice the period of time for which progression was documented prior to entry into this study (criteria of the AIO phase I/II-study group). Progressive disease was observed in 17 patients with 3 early deaths. Severe side effects were seen in the gastrointestinal tract as abdominal pain, loss of appetite, nausea and vomiting (up to grade 4, WHO) or diarrhea (up to grade 2, WHO). In conclusion, oral MIL given daily showed no major therapeutic activity in patients with NSCLC.
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