Targretin
Cutaneous T-cell lymphoma (CTCL) — cutaneous manifestations in patients refractory to at least one prior systemic therapy (oral); Early-stage CTCL (stage IA-IIA) refractory to or persistent despite prior therapies or intolerant of other therapies (topical gel).
Oral: 300 mg/m²/day as a single daily dose with food
If no response at 8 weeks and well-tolerated, may increase to 400 mg/m²/day
May reduce to 200 mg/m²/day then 100 mg/m²/day for toxicity
Topical gel: Apply sufficient gel to cover lesion every other day for first week, then once daily. Increase to BID, TID, then QID at weekly intervals as tolerated. Most patients require BID-QID.
Capsules: 75 mg; Topical gel: 1%
Pregnancy (Category X — retinoid; mandatory pregnancy prevention). Nursing mothers.
- Lipid Abnormalities: Triglycerides elevated in 79% (>500 mg/dL in 30%). Total cholesterol elevated in 48%. Fasting lipid panel before, at 2-4 weeks, then periodically. Treat hyperlipidemia and consider dose reduction.
- Central Hypothyroidism: In 29-40%. TSH normal but free T4 low (RXR activation suppresses TSH). Monitor thyroid function and supplement with levothyroxine.
- Pancreatitis: Due to hypertriglyceridemia. Has been fatal.
- Hepatotoxicity: Monitor LFTs.
- Leukopenia: In 17%. Monitor CBC.
- Cataracts: Reported in preclinical studies. Ophthalmologic exam recommended.
- Photosensitivity: Avoid excessive sunlight/UV exposure.
- Pregnancy (Category X): Mandatory pregnancy test within 1 week, effective contraception.
Hyperlipidemia (79%), headache (30%), hypothyroidism (29%), asthenia (20%), leukopenia (17%), rash (14%), nausea (13%), infection (13%), peripheral edema (11%), diarrhea (7%), abdominal pain (11%), dry skin (9%)
Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.
Bexarotene selectively activates retinoid X receptors (RXRα, RXRβ, RXRγ), which are members of the nuclear receptor superfamily. RXR activation forms heterodimers with multiple nuclear receptor partners (RAR, PPARs, VDR, thyroid receptor) and modulates gene expression involved in cellular differentiation, proliferation, and apoptosis. In CTCL, RXR activation induces growth arrest and apoptosis of malignant T cells. The precise mechanism of anti-tumor activity in CTCL is not fully established but involves modulation of multiple retinoid-responsive pathways.
Tmax: approximately 2 hours. Half-life: approximately 7 hours. Protein binding: >99%. Metabolized by CYP3A4 (auto-induces own metabolism). Excreted primarily in hepatobiliary system. Food increases bioavailability ~48%. Plasma levels may decrease over time due to CYP3A4 auto-induction.
Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.
- Bexarotene Phase III — Bexarotene in advanced-stage CTCL refractory to ≥1 prior systemic therapy. Phase II/III, n=94.