Results of a prospective phase II trial with oral low-dose bexarotene plus photochemotherapy (PUVA) in refractory and/or relapsed patients with mycosis fungoides
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Bexarotene is a synthetic retinoid effective in early and advanced stages of mycosis fungoides (MF)/Sezary Syndrome (SS) both in monotherapy and combination schemes.
We aimed to assess disease response to low-dose bexarotene and PUVA in maintenance in refractory and/or resistant patients with early and advanced stage MF/SS.
We followed prospectively 21 patients (stages IB-IV): 15 with early stage MF and 6 with advanced disease. “Mini” and standard protocols were respectively applied to patients who failed PUVA or several systemic regimens. The dose of bexarotene and the administration of PUVA were titrated individually and tailored during induction and maintenance according to previous therapy, disease stage and toxicity. We evaluated overall response (OR) at the end of maintenance, safety and event-free survival (EFS).
After induction phase, OR was 85.6%, higher in early MF (93.4%) than in advanced disease (66.6%). At the end of maintenance, OR was 76.2%, including 33.3% of CR. Median EFS for the whole group was 31 months. Bexarotene was well tolerated regarding the side effects, with prophylaxis and progressive drug increase in the induction phase of the protocol. Side effects were mainly of low and moderate grades.
We observed a favorable rate of therapeutic effects and few, generally mild, side effects with low doses of bexarotene combined with PUVA.
Key wordsmycosis fungoides bexarotene PUVA
Cutaneous T-cell Lymphomas
Event Free Survival
European Organisation for Research and Treatment of Cancer
International Society for Cutaneous Lymphomas
Overall Response Rate
Per os/by mouth/orally
PS-341 Anthracycline Dexamethasone
Pegylated liposomal doxorubicin
Psoralen and Ultraviolet A
Retinoid X Receptor
Severity Weighted Assessment Tool
Total Body Surface Area
Tumor Node Metastatic Blood
World Health Organization
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- 3.Rupoli S, Goteri G, Pulini S, et al. Long-term experience with lowdose interferon-alpha and PUVA in the management of early mycosis fungoides. Marche Regional Multicentric Study Group of Cutaneous Lymphomas. Eur J Haematol 2005; 75: 136–45.Google Scholar
- 5.Duvic M, Martin AG, Kim Y, et al. Phase 2 and 3 clinical trial of oral bexarotene (Targretin capsules) for the treatment of refractory or persistent early-stage cutaneous T-cell lymphoma. Worldwide Bexarotene Study Group. Arch Dermatol 2001; 137: 581–93.Google Scholar
- 6.Duvic M, Hymes K, Heald P, et al. Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. Bexarotene Worldwide Study Group. J Clin Oncol 2001; 19: 2456–71.Google Scholar
- 9.Whittaker S, Ortiz P, Dummer R, 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.CrossRefPubMedGoogle Scholar
- 11.Swerdlow SH, Campo E, Harris NL, et al. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press, 2008.Google Scholar
- 12.Olsen E, Vonderheid E, Pimpinelli N, et al. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood 2007; 110: 1713–22.CrossRefPubMedGoogle Scholar
- 17.Shapiro M, Rook AH, Lehrer MS, Junkins-Hopkins JM, French LE, Vittorio CC. Novel multimodality biologic response modifier therapy, including bexarotene and long-wave ultraviolet A for a patient with refractory stage IVa cutaneous T-cell lymphoma. J Am Acad Dermatol 2002; 47: 956–61.CrossRefPubMedGoogle Scholar
- 19.Beltrand B, Paredes A, Moises C, et al. Low dose Bexarotene and phototherapy or Interferon alpha -2a in the treatment of patients with relapsed or refractory cutaneous T-cell lymphoma. Blood (ASH Annual Meeting Abstract) 2008 112:abs 5010.Google Scholar
- 21.Straus DJ, Duvic M, Horwitz SM, et al. Interim results of phase II trial of pegylated liposomal Doxorubicin (PLD) followed by bexarotene in advanced cutaneous T-cell lymphoma: (CTCL). ASCO 2010 Annual Meeting Abstract n. 8053.Google Scholar