title: Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results.
abstract: OBJECTIVE
  Cutaneous T-cell lymphomas (CTCL) are malignancies of T cells appearing as skin lesions and are responsive to retinoid therapy. Safety and efficacy of a novel RXR-selective retinoid (rexinoid) bexarotene (Targretin, LGD1069; Ligand Pharmaceuticals Inc, San Diego, CA) was evaluated as a single-agent oral therapy administered once daily in an open-label study in patients with refractory advanced-stage CTCL.
  
  
  METHODS
  Ninety-four patients with biopsy-confirmed CTCL in advanced stages (IIB-IVB) were enrolled at 26 centers. Fifty-six patients received an initial dose of 300 mg/m2/d oral bexarotene and 38 started at more than 300 mg/m2/d.
  
  
  RESULTS
  Clinical complete and partial responses were reported by Primary End point Classification for the study in 45% (25 of 56) of patients enrolled at 300 mg/m2/d dosing. At more than 300 mg/m2/d, 55% (21 of 38) of patients responded, including 13% (five of 38) clinical complete. For the 300 mg/m2/d initial dose group, the rate of relapse after response was 36% and the projected median duration of response was 299 days. Improvements were also seen in overall body-surface area involvement, median index lesion surface area, adenopathy, cutaneous tumors, pruritus, and CTCL-specific quality of life. The most frequent drug-related adverse events included hypertriglyceridemia (associated rarely with pancreatitis), hypercholesterolemia, hypothyroidism, and headache.
  
  
  CONCLUSIONS
  Bexarotene is the first in a novel class of pharmacologic agents, the RXR-selective retinoids, or rexinoids. Bexarotene is orally administered, safe, and generally well tolerated with reversible side effects, and is effective for the treatment of advanced, refractory CTCL.
authors.affiliation: M.D. Anderson Cancer Center, Houston, TX.
authors.forename: M
authors.initials: M
authors.lastname: Duvic
authors.forename: K
authors.initials: K
authors.lastname: Hymes
authors.forename: P
authors.initials: P
authors.lastname: Heald
authors.forename: D
authors.initials: D
authors.lastname: Breneman
authors.forename: A G
authors.initials: AG
authors.lastname: Martin
authors.forename: P
authors.initials: P
authors.lastname: Myskowski
authors.forename: C
authors.initials: C
authors.lastname: Crowley
authors.forename: R C
authors.initials: RC
authors.lastname: Yocum
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000077610:Bexarotene; D005260:Female; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D013764:Tetrahydronaphthalenes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D016588:Anticarcinogenic Agents; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene