To review the preclinical and clinical information related to oral bexarotene approved by the Food and Drug Administration for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) in patients who are refractory to at least one prior systemic therapy.
DATA SOURCES:
Literature accessed through MEDLINE (from 1990 to July 2000) and provided by the manufacturer. Key search terms included bexarotene, Targretin, LGD1069, and cutaneous T-cell lymphoma.
DATA SYNTHESIS:
The management of CTCL remains controversial due to its rarity in the US and its heterogeneity. An evaluation focusing on the pharmacology of bexarotene and its role in the management of the different stages of CTCL was conducted.
CONCLUSIONS:
Bexarotene has demonstrated activity in the treatment of CTCL. The oral route of administration and the adverse effect profile of bexarotene appear to make this drug a favorable option for the treatment of CTCL compared with other systemic therapies. Phase III randomized studies are needed to determine the clinical benefits of bexarotene as monotherapy or combination therapy in the treatment of CTCL.
KimYHoppeR. Mycosis fungoides and the Sézary syndrome. Semin Oncol1999; 26: 276–89.
2.
WilsonLKacinskiBEdelsonRHealdP. Cutaneous T-cell lymphomas. In: DeVitaVHellmanSRosenbergS, eds. Cancer principles & practice of oncology. 5th ed.Philadelphia: Lippincott-Raven1997: 2220–33.
3.
SiegelRPandolfinoTGuitartJRosenSKezelT. Primary cutaneous T-cell lymphoma: Review and current concepts. J Clin Oncol2000; 18: 2909–25.
4.
WillemzeRKerlHSterryWBertiECerroniLChimentiS. EORTC classification for primary cutaneous lymphomas: A proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood1997; 90: 354–71.
5.
KimYJensenRWatanabeGVargheseAHoppeR. Clinical stage IA (limited patch and plaque) mycosis fungoides: A long-term outcome analysis. Arch Dermatol1996; 132: 1309–13.
6.
ZackheimHAminSKashani-SabetMMcMillianA. Prognosis in cutaneous T-cell lymphoma by skin stage: Long term survival in 489 patients. J Am Acad Dermatol1999; 40: 418–25.
7.
DuvicMMartinAKimYOlsenEWoodGYocumR. Oral bexarotene is safe and effective in a Phase II—III clinical trial in refractory or persistent early stage CTCL (abstract 2927). Blood1999; 94 (suppl 1part 1):659a.
8.
DuvicMMartinAKimYOlsenEWoodG, and the Worldwide Bexarotene Study Group. Phase II—III clinical trial of bexarotene capsules demonstrated efficacy and safety for patients with refractory or persistent early stage CTCL (abstract 231). Poster presented at the 58th Annual Meeting of the American Academy of Dermatology, San Francisco, March 10–15, 2000.
9.
DuvicMHymesKHealdPBrenemanDMartinAMyskowskiP. Phase II—III clinical trial of bexarotene capsules in patients with refractory advanced stage CTCL demonstrates efficacy and safety (abstract 60). Poster presented at the 58th Annual Meeting of the American Academy of Dermatology, San Francisco, March 10–15, 2000.
MillerVBenedettiFRigasJVerretAPfisterDStrausD. Initial clinical trial of a selective retinoids X receptor ligand, LGD1069. J Clin Oncol1997; 15: 790–5.
12.
RizviNMarshallJDahutWNessETrugliaJLoewenG. A Phase I study of LGD1069 in adults with advanced cancer. Clin Cancer Res1999; 5: 1658–64.
13.
Package insert. Targretin capsules (bexarotene). February 2000. San Diego, CA: Ligand Pharmaceuticals, February 2000.
14.
BoehmMZhangLBadeaBWhiteSMaisDBergerE. Synthesis and structure-activity relationships of novel retinoid X receptor—selective retinoids. J Med Chem1994; 37: 2930–42.
15.
HealdPDuvicM. Palliation and remission of erythrodermic cutaneous T-cell lymphoma with a novel oral RXR—selective retinoid (abstract 428). Poster presented at the 58th Annual Meeting of the American Academy of Dermatology, San Francisco, March 10–15, 2000.
16.
FromerM. Targretin approved for advanced CTCL following ODAC recommendation. Oncol Times2000(Jan):45–8.
17.
OdujinrinOJohnsonJ. Targretin (bexarotene) capsules. Ligand Pharmaceuticals. ASCO News FDA Report. April 2000: 38.
18.
ShermanSGopalJHugenBChiuAWhaleyKNowlakhaP. Central hypothyroidism associated with retinoid X receptor—selective ligands. N Engl J Med1999; 340: 1075–9.
19.
HeinNHowellSUlmE. Evaluation of the cytochrome P450 isoenzymes involved in the metabolism of Targretin, an RXR-selective retinoid. Proceedings of the 7th North American ISSX Meeting, San Diego, October 20–24, 1996: 364.
20.
ZackheimHKashani-SabetMAminS. Topical corticosteroids for mycosis fungoides. Arch Dermatol1998; 134: 949–54.
21.
ZackheimHS. Cutaneous T-cell lymphoma: Update of treatment. Dermatology1999; 199: 102–5.
22.
RamseyDMellerJZackheimH. Topical treatment of early cutaneous T-cell lymphoma, Hematol Oncol Clin North Am1995;9: 1031–56.
23.
HoppeRT. Total skin electron beam therapy in the management of mycosis fungoides. Front Radiat Ther Oncol. Basel, Switzerland: Karger, 1991; 25: 80–9.
24.
ResnickKSVonderheidEC. Home UV phototherapy for early mycosis fungoides: Long-term follow-up observations in thirty-one patients. J Am Acad Dermatol1993; 29: 73–7.
25.
HermannJRoenigkHJHurriaAKuzelTMSamuelsonEMRademakerAW. Treatment of mycosis fungoides with photochemotherapy (PUVA): Long-term follow-up. J Am Acad Dermatol1995; 33: 234–42.
26.
ZackheimHSEpsteinEHJr.CrainWR. Topical carmustine (BCNU) for cutaneous T-cell lymphoma. J Am Acad Dermatol1990; 22: 802–10.
27.
HealdPRookAPerezMWintroubBKnoblerRJegasothyB. Treatment of erythrodermic cutaneous T-cell lymphoma by extracorporeal photochemotherapy. J Am Acad Dermatol1992; 27: 427–33.
28.
Fraser-AndrewsESeedPWhittakerSRussell-JonesR. Extracorporeal photopheresis in Sézary syndrome. No significant effect in the survival of 44 patients with a peripheral blood T-cell clone. Arch Dermatol1998; 134: 1001–5.
29.
ZackheimHKashani-SaberMHwangS. Low-dose methotrexate to treat erythrodermic cutaneous T-cell lymphoma: Results in twenty-nine patients. J Am Acad Dermatol1996; 34: 626–31.
30.
RosenSFossF. Chemotherapy for mycosis fungoides and the Sézary syndrome. Hematol Oncol Clin North Am1995; 9: 1109–16.
31.
ZaknoenS. Nucleoside analogs in the systemic treatment of mycosis fungoides/Sézary syndrome. J Geriatr Dermatol1997; 5: 364–9.
32.
FierroMTQuaglinoPSavoiaPVerroneABernengoMG. Systemic polychemotherapy in the treatment of primary cutaneous lymphomas: A clinical follow-up study of 81 patients treated with COP or CHOP. Leuk Lymphoma1998; 31: 583–8.
ZackheimH. Treatment of cutaneous T cell lymphoma with retinoids. Dermatologic Ther1998; 7: 15–20.
35.
KuzelTRoenigkHJSamuelsonEHerrmannJHurriaARademakerA. Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sézary syndrome. J Clin Oncol1995; 13: 257–63.
36.
FossFMIhdeDCLinnoilaIRFischmannABSchechterGPCotelingamJD. Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome. J Clin Oncol1994; 12: 2051–9.
37.
Product information. Ontak (denileukin diftitox). San Diego: Ligand Pharmaceuticals, February 1999.
38.
HealdPMehlmauerMMartinAGOlsenECrowleyCYocumR. The benefits of topical bexarotene in patients with refractory or persistent early stage cutaneous T-cell lymphoma: Results of the phase 3 clinical trial (abstract). Invest Dermatol2000; 114: 840.
39.
ZinzaniPLBalivaGMagagnoliMBendandiMModugnoGGherlinzoniF. Gemcitabine treatment in pretreated cutaneous-T-cell lymphoma: Experience in 44 patients. J Clin Oncol2000; 18: 2603–6.
40.
DuvicMCatherJ. Emerging new therapies for cutaneous T-cell lymphoma. Dermatol Clin2000; 18: 147–56.
41.
GottardisMBischoffEShirleyMWagonerMLamphWHeymanR. Chemoprevention of mammary carcinoma by LGD1069 (Targretin): An RXR-selective ligand. Cancer Res1996; 56: 5566–70.
42.
BischoffEHeymanRLamphW. Effect of the retinoid X receptor—selective ligand LGD1069 on mammary carcinoma after tamoxifen failure. J Natl Cancer Inst1999; 91: 2118–23.
43.
BischoffEGottardisMMoonTHeymanRLamphW. Beyond tamoxifen: The retinoid X receptor—selective ligand LGD1069 (Targretin) causes complete regression of mammary carcinoma. Cancer Res1998; 58: 479–84.
44.
2001 Drug topics red book. Montvale, NJ: Medical Economics Company, 2001.
