Optimizing bexarotene therapy for cutaneous T-cell lymphoma

• Published in: Journal of the American Academy of Dermatology 2002-11, Vol.47 (5), p.672-684
• Main Authors: Talpur, Rakhshandra, Ward, Staci, Apisarnthanarax, Narin, Breuer-McHam, Joan, Duvic, Madeleine
• Format: Article
• Language: English
• Subjects: Algorithms; Anticarcinogenic Agents - administration & dosage; Anticarcinogenic Agents - adverse effects; Anticarcinogenic Agents - therapeutic use; Bexarotene; Biological and medical sciences; Dermatitis, Exfoliative - complications; Dermatitis, Exfoliative - therapy; Dermatology; Drug Therapy, Combination; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypertriglyceridemia - complications; Hypertriglyceridemia - drug therapy; Hypothyroidism - chemically induced; Medical sciences; Middle Aged; Mycosis Fungoides - complications; Mycosis Fungoides - drug therapy; Pharmacology. Drug treatments; Photopheresis; Prospective Studies; Skin Neoplasms - complications; Skin Neoplasms - drug therapy; Skin, nail, hair, dermoskeleton; Tetrahydronaphthalenes - administration & dosage; Tetrahydronaphthalenes - adverse effects; Tetrahydronaphthalenes - therapeutic use; Treatment Outcome; Tumors of the skin and soft tissue. Premalignant lesions
• ISSN: 0190-9622; 1097-6787
• DOI: 10.1067/mjd.2002.124607

Background: Bexarotene (Targretin oral capsules), the first RXR-selective retinoid “rexinoid” approved for all stages of cutaneous T-cell lymphoma (CTCL), had a response rate (RR) of 45% at the optimal dose of 300 mg/m2 per day in 2 multicenter trials. With hypertriglyceridemia reported at 79%, bexarotene is often administered with lipid-lowering agents (LLAs). Statins (inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase) may modulate class II major histocompatibility class expression and T-cell responses. Objective: We attempted to optimize the clinical response to bexarotene by controlling dose-limiting hypertriglyceridemia and combining bexarotene with other active agents. Methods: We prospectively evaluated 70 patients with CTCL at M. D. Anderson Cancer Center who were treated with oral bexarotene as monotherapy or in combination with other active agents. Results: Fifty-four patients receiving bexarotene monotherapy achieved an overall RR of 48%. Thirteen had stage IA-IIA disease (RR = 53%, 1 complete response [CR]); 41 had stage IIB-IVB disease (RR = 46%, 2 CRs). Forty-two (77%) of these also required one or more LLAs: atorvastatin (n = 29, RR 43%), atorvastatin plus fenofibrate (n = 10, RR 90%), or gemfibrozil (n = 3, RR 33%). Gemfibrozil was discontinued because it increased bexarotene and triglyceride levels. Patients taking 2 LLAs had a significantly higher RR of 90% during monotherapy than those taking one or no LLAs (P < .0001). Forty of 54 patients (74%) received thyroid hormone replacement to normalize thyroxine levels. Four patients receiving monotherapy have complete CRs of >3 years' duration and received maintenance dosing. Sixteen patients with advanced disease treated with bexarotene (225-750 mg/d) in combination with other CTCL therapies achieved an overall RR of 69% (11/16) with concomitant statin therapy. Bexarotene was safely combined with psoralen ultraviolet A (PUVA) plus interferon alfa (IFN-α) (n = 2, RR = 50%), with extracorporeal photopheresis (ECP) (n = 8, RR = 75%, 1 CR), with ECP/IFN-α (n = 4, RR =50%), with ECP/IFN-α/PUVA (n = 1, RR = 100%), and with IFN-α/PUVA/topical nitrogen mustard (n = 1, RR = 100%). Two patients receiving IFN-α had slight leukopenia, but rhabdomyolysis associated with multiple LLAs did not occur. Conclusion: This single-center study supports the safety and efficacy of bexarotene as both a monotherapy and a combination therapy for CTCL. Long durable CRs may be achieved with oral monotherapy. U