Daily Oral Miltefosine (Hexadecylphosphocholine) in Patients with Advanced Breast Cancer: A Phase II Study

Unger, Clemens; Becher, R.; Rieche, K; Wander, H.-E.; Friedrich, G.; Edler, Lutz

doi:10.1159/000218271

Cited by 5 publications

(2 citation statements)

References 9 publications

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“…In the study by Berdel et al [28,29], 70% of the lung cancer patients treated with MF for nine weeks experienced episodes of nausea and vomiting. In the study of Unger et al [30], nearly 90% of the breast cancer patients experienced gastrointestinal side effects when treated with 100–150 mg MF daily for nine weeks. Similar results were found in a phase II trial where 90% of the cancer patients experienced episodes of nausea and vomiting when treated with MF for six weeks [31].…”

Section: Discussionmentioning

confidence: 99%

The safety and efficacy of miltefosine in the long-term treatment of post-kala-azar dermal leishmaniasis in South Asia – A review and meta-analysis

et al. 2019

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Background Miltefosine (MF) is the only oral drug available for treatment of visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). Although the drug is effective and well tolerated in treatment of VL, the efficacy and safety of MF for longer treatment durations (>28 days) in PKDL remains unclear. This study provides an overview of the current knowledge about safety and efficacy of long treatment courses with MF in PKDL, as a strategy in the VL elimination in South Asia. Methodology/Principal findings Literature was searched systematically for articles investigating MF treatment in PKDL. A meta-analysis included eight studies (total 324 PKDL patients) to estimate the efficacy of MF in longer treatment regimens (range 6–16 weeks). We found a per-protocol (PP) initial cure rate of 95.2% (95%CI 89.6–100.8) and a PP definite cure rate of 90% (95%CI 81.6–96.3). Descriptive analysis showed that 20% of patients experienced adverse events, which mostly had an onset in the first week of treatment and were likely to get more severe after four weeks of treatment. Gastrointestinal (GI) side effects such as vomiting, nausea, diarrhoea, and abdominal pain were most common. Conclusions/Significance Longer treatment regimens with MF are effective in PKDL patients in India, however with the caveat that the efficacy has recently been observed to decline. GI side effects are frequent, although mostly mild or moderate. However, on the basis of limited data, we cannot conclude that longer MF treatment regimens are safe. Moreover, VL and PKDL pharmacovigilance studies indicate a risk for serious adverse events, questioning the safety of MF. The provision of safer treatment regimens for PKDL patients are therefore recommended. Until these regimens are identified, it should be considered to halt the use of MF monotherapy for PKDL in order to preserve the drug’s efficacy.

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Section: Discussionmentioning

confidence: 99%

The safety and efficacy of miltefosine in the long-term treatment of post-kala-azar dermal leishmaniasis in South Asia – A review and meta-analysis

et al. 2019

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“…A phase II dose-finding study in cancer patients confirmed previous phase I data showing that the major dose-limiting toxicity effects were nausea and vomiting and suggested a maximum dose of 150 mg/d split into three doses (Verweij et al, 1992). Oral treatment was subsequently tested in a number of oncological trials, including a phase II study for treatment of soft tissue sarcomas (Verweij et al, 1993b), a phase II study in advanced nonsmall cell lung cancer (Berdel et al, 1992), a phase II study in advanced colorectal cancer (Planting et al, 1993), a phase II study in advanced breast cancer (Unger et al, 1993), and a phase II study for squamous cell head and neck cancer (Verweij et al, Fig. 1.…”

Section: Development Of Miltefosine For Oncologymentioning

confidence: 99%

Repurposing Miltefosine for the Treatment of Immune-Mediated Disease?

Verhaar

Wildenberg

Peppelenbosch

et al. 2014

The Journal of Pharmacology and Experimental Therapeutics

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Miltefosine is an ether lipid that was initially developed for cancer treatment in the early 1980s. Miltefosine largely failed development for oncology, although it was approved for the topical treatment of breast cancer metastasis. It was subsequently discovered that miltefosine is a highly effective treatment of visceral Leishmaniasis, a parasitic disease that affects millions worldwide and causes an estimated 30,000 fatalities each year. Oral treatment with miltefosine is generally well tolerated and has relatively few adverse effects. The exact mechanism of action of miltefosine treatment is still under investigation. Its close resemblance to phospholipids allows it to be quickly taken up by cell membranes and affect related processes, such as lipid metabolism and signaling through lipid rafts. These processes play an important role in the immune response and it comes as no surprise that miltefosine has been successfully tested for the treatment of a number of immune-mediated diseases in preclinical models of disease. Drug repurposing of miltefosine for immunemediated diseases may provide an opportunity to expand the limited number of drugs that are currently available for therapeutic use.

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