DefinitionThis section has been translated automatically.
Cytostatically active synthetic retinoid.
Pharmacodynamics (Effect)This section has been translated automatically.
The exact mechanism of action is not yet fully understood. The activation of selective retinoid X-receptors (RXRs) or RAR (retiniod-acid receptor), which are important in cell metabolism (vitamin D3 thyroid hormone receptor, proliferation-activating receptor in peroxysomes), is being discussed. The retinoid-activated retinoid receptors form homo- or heterodimers that bind to specific DNA sequences and act as transcription factors for genes. RAR regulates cell growth and differentiation, RXR regulates apoptosis. Bexarotene can therefore directly intervene in the regulation of apoptosis.
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IndicationThis section has been translated automatically.
Approved indication: Patients with advanced stage cutaneous T-cell lymphoma (CTCL) (stages IIb-IVb) who have not responded to at least one systemic therapy.
Limited indicationThis section has been translated automatically.
Current studies show that patients with cutaneous T-cell lymphomas of the mycosis fungoides type, patients with Sézary syndrome and lymphomatoid papulosis benefit from Bexarotene.
Pregnancy/nursing periodThis section has been translated automatically.
Insufficient data on use in pregnancy. In animal studies, indications of damage to embryonic cells (reproductive toxicity). The drug should not be prescribed during pregnancy!
Dosage and method of useThis section has been translated automatically.
- Initial: once/day 300 mg/m2 KO/day p.o., later the dose can be reduced to 100-200 mg/m2 KO p.o. The treatment should be continued as long as it is beneficial for the patients (in studies up to 118 weeks).
- Successful individual trials were achieved with a 1% gel application (4 times daily).
Undesirable effectsThis section has been translated automatically.
- Systemic use: hypertriglyceridemia, hypothyroidism, hypercholesterolemia, headache, leukopenia, pruritus, general fatigue. As with other retinoids, typical mucocutaneous toxicity. Less common are exfoliative exanthema and diffuse pain symptoms. Above all the disturbance of the fat metabolism requires close control, as does hypothyroidism. Possibly substitution of the thyroid hormones.
- With local application: erythema, blistering, pruritus, pain.
PreparationsThis section has been translated automatically.
Targretin
Note(s)This section has been translated automatically.
- Pregnancy must be ruled out before the start of therapy and patients must be informed about effective contraception until at least one month after the end of therapy (2 contraceptive methods simultaneously; non-hormonal anticontraception preferred).
- Studies showed that patients remained progression-free for a median of about 40 weeks. The time to response is about 16 weeks! Educate the patient about this long start-up period.
- Combination therapies are possible, including PUVA therapy, interferons, extracorporeal photopheresis.
LiteratureThis section has been translated automatically.
- Hanson M et al (2003) Bexarotene reverses alopecia in cutaneous T-cell lymphoma. Br J Dermatol 149: 193-196
- Kliewer SA et al (1992) Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature 358: 771-774
- Kliewer SA et al (1992) Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling. Proc Natl Acad Sci USA 89: 1448-1452
- Kliewer SA et al (1992) Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature 355: 446-449
- Lowe MN et al (2000) Bexarotene. At J Clin Dermatol 1: 245-250
- Martin AG et al (2003) Bexarotene gel: a new skin-directed treatment option for cutaneous T-cell lymphomas. J Drugs Dermatol 2: 155-167
- McGinnis KS et al (2003) Psoralen plus long-wave UV-A (PUVA) and bexarotene therapy: An effective and synergistic combined adjunct to therapy for patients with advanced cutaneous T-cell lymphoma. Arch Dermatol 139: 771-775
- Stern DK et al (2002) Treatment of mycosis fungoides with orally bexarotene combined with PUVA. J Drugs Dermatol 1: 134-136
- Talpur R et al (2002) Optimizing bexarotene therapy for cutaneous T-cell lymphoma. J Am Acad Dermatol 47: 672-684
Prof. Dr. med. Peter Altmeyer