OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULAS AND STRUCTURES

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Bexarotene	153559-49-0	C24-H28-O2
Vitamin A	68-26-8	C20-H30-O

ANNOTATED BIBLIOGRAPHY

References updated: 26 September 2017

Abbreviations: CTCL, cutaneous T cell lymphoma

• Zimmerman HJ. Hepatotoxic effects of oncotherapeutic and immunosuppressive agents. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 673-708.

  (Expert review of hepatotoxicity of cancer chemotherapeutic agents published in 1999; discusses liver injury from retinoids, but not specifically bexarotene).
• DeLeve LD. Cancer chemotherapy. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 541-68.

  (Review of hepatotoxicity of cancer chemotherapeutic agents; bexarotene is not discussed).
• Burkhart C, Morrell D, Goldsmith L. Dermatological pharmacology. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp 1803-32.

  (Textbook of pharmacology and therapeutics).
• Bexarotene (Targretin) for cutaneous T-cell lymphoma. Med Lett Drugs Ther 2000; 42 (1075): 31-2. [PubMed: 10788961]

  (Concise review of the mechanism of action, clinical efficacy, adverse effects and costs of bexarotene shortly after its approval in the US; mentions that “elevations in aminotransferase concentrations have occurred, and fatal pancreatitis and fatal cholestasis have been reported”).
• Duvic M, Hymes K, Heald P, Breneman D, Martin AG, Myskowski P, Crowley C, et al.; Bexarotene Worldwide Study Group. Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. J Clin Oncol 2001; 19: 2456-71. [PubMed: 11331325]

  (Among 94 patients with advanced and refractory CTCL treated with bexarotene, clinical responses occurred in 45-55% and side effects were common but usually mild, but led to early termination of therapy in 10%; AST elevations occurred during the first month of treatment in 20% of patients).
• Duvic M, Martin AG, Kim Y, Olsen E, Wood GS, Crowley CA, Yocum RC; Worldwide Bexarotene Study Group. Phase 2 and 3 clinical trial of oral bexarotene (Targretin capsules) for the treatment of refractory or persistent early-stage cutaneous T-cell lymphoma. Arch Dermatol 2001; 137: 581-93. [PubMed: 11346336]

  (Among 58 patients with refractory or persistent CTCL treated with bexarotene at different doses, clinical responses occurred in 56% given 300 mg/m² daily, while adverse side effects were common and ALT or AST elevations of 2.5 to 5 times ULN occurred in 10%).
• Esteva FJ, Glaspy J, Baidas S, Laufman L, Hutchins L, Dickler M, Tripathy D, et al. Multicenter phase II study of oral bexarotene for patients with metastatic breast cancer. J Clin Oncol 2003; 21: 999-1006. [PubMed: 12637463]

  (Among 145 women with metastatic breast cancer treated with bexarotene, clinical responses were uncommon and usually partial, while adverse events included hypertriglyceridemia [84%], dry skin [34%], weakness [30%] and headache [27%] and two patients [1%] had dose limiting liver test elevations).
• Smit JV, Franssen ME, de Jong EM, Lambert J, Roseeuw DI, De Weert J, Yocum RC, et al. A phase II multicenter clinical trial of systemic bexarotene in psoriasis. J Am Acad Dermatol 2004; 51: 249-56. [PubMed: 15280844]

  (Among 50 patients with severe psoriasis treated with bexarotene in 4 doses for 12-24 weeks, clinical responses occurred in 22-52% of patients and adverse events included hypertriglyceridemia [56%], decrease in serum free T4 levels [54%], fatigue [14%], pruritus [14%] and ALT elevations [6%]).
• Kannangara AP, Levitan D, Fleischer AB Jr. Evaluation of the efficacy of the combination of oral bexarotene and methotrexate for the treatment of early stage treatment-refractory cutaneous T-cell lymphoma. J Dermatolog Treat 2009; 20: 169-76. [PubMed: 19016373]

  (Among 12 patients with refractory CTCL treated with methotrexate and bexarotene, partial responses occurred in 58%, but one patient who had received 13 g of methotrexate developed grade 3 “liver failure”).
• Väkevä L, Ranki A, Hahtola S. Ten-year experience of bexarotene therapy for cutaneous T-cell lymphoma in Finland. Acta Derm Venereol 2012; 92: 258-63. [PubMed: 22678563]

  (Description of 37 Finnish patients with CTCL treated with bexarotene focusing on management of adverse reactions including hypertriglyceridemia and hypothyroidism; mentions that 4 patients [11%] had ALT or AST elevations above 5 times ULN, but the levels returned to normal upon stopping, although they recurred in 1 of 2 patients who restarted therapy at a lower dose).
• Whittaker S, Ortiz P, Dummer R, Ranki A, Hasan B, Meulemans B, Gellrich S, et al. Efficacy and safety of bexarotene combined with psoralen-ultraviolet A (PUVA) compared with PUVA treatment alone in stage IB-IIA mycosis fungoides: final results from the EORTC Cutaneous Lymphoma Task Force phase III randomized clinical trial (NCT00056056). Br J Dermatol 2012; 167: 678-87. [PubMed: 22924950]

  (Among 87 patients with mycosis fungoides treated with psoralen with ultraviolet A [PUVA] with or without bexarotene, overall response rates were similar [77% vs 71%], but side effects were greater with the combination including ALT elevations above 5 times ULN [8.7% vs 0%]).
• Lerner V, Miodownik C, Gibel A, Sirota P, Bush I, Elliot H, Benatov R, et al. The retinoid X receptor agonist bexarotene relieves positive symptoms of schizophrenia: a 6-week, randomized, double-blind, placebo-controlled multicenter trial. J Clin Psychiatry 2013; 74: 1224-32. [PubMed: 24434091]

  (Among 90 patients with schizophrenia treated with bexarotene [75 mg daily] or placebo for 6 weeks, serum ALT and AST levels did not change significantly in either group).
• Hamada T, Sugaya M, Tokura Y, Ohtsuka M, Tsuboi R, Nagatani T, Tani M, et al. Phase I/II study of the oral retinoid X receptor agonist bexarotene in Japanese patients with cutaneous T-cell lymphomas. J Dermatol 2017; 44: 135-42. [PubMed: 27543197]

  (Among 16 patients with cutaneous T cell lymphomas treated with bexarotene for 24 weeks, ALT elevations were reported in 4 [25%] and led to early discontinuation in 1 [6%].