THERAPEUTICS BJD British Journal of Dermatology 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 21011 (NCT00056056) S. Whittaker, 1 P. Ortiz, 2 R. Dummer, 3 A. Ranki, 4 B. Hasan, 5 B. Meulemans, 5 S. Gellrich, 6 R. Knobler, 7 R. Stadler 8 and M. Karrasch 5 1 St John’s Institute of Dermatology, King’s College London, London, U.K. 2 Department of Dermatology, Hospital Universitario 12 de Octubre, Madrid, Spain 3 Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland 4 Department of Dermatology and Allergic Diseases, Helsinki University Hospital, Helsinki, Finland 5 European Organization for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium 6 Charite ´ University Hospital – Campus Mitte, Berlin, Germany 7 Department of Dermatology, Medical University Vienna, Vienna, Austria 8 Department of Dermatology, Johannes Wesling Klinikum, Minden, Germany Correspondence Matthias Karrasch. E-mail: karraschm@yahoo.com Accepted for publication 30 June 2012 Funding sources This publication was supported by educational grants from Ligand Pharmaceuticals Inc. ⁄ Eisai Co., Ltd. and by a donation from Cancer Research U.K. through the EORTC Charitable Trust. Conflicts of interest None declared. DOI 10.1111/j.1365-2133.2012.11156.x Summary Background Psoralen plus ultraviolet A (PUVA) is the standard treatment for early stages of mycosis fungoides. There have been no adequate randomized controlled trials with sufficient power comparing this modality with other therapies. Objective To assess disease response and to compare the response rates of patients trea- ted with PUVA alone or PUVA and bexarotene. Methods EORTC 21011 (NCT 00056056) was a randomized phase III study comparing combined bexarotene (Targretin Ò ) and PUVA vs. PUVA alone in patients with stage IB and IIA mycosis fungoides (MF). The primary endpoint was the overall response rate [complete clinical response (CCR) plus partial response (PR)]. Results The study was prematurely closed due to low accrual after 93 of 145 required patients (65%) were randomized. Of the 93 randomized patients, 87 started treatment, 41 received PUVA and 46 received PUVA + bexarotene. Total UVA doses received were 107 J cm )2 (range 1Æ4–489Æ9) in the PUVA arm vs. 101Æ7 J cm )2 (0Æ2–529Æ9) in the combination arm. The safety profile was acceptable with few grade 3–4 toxicities observed in either arm. More drop-outs due to toxicity were observed in the combin- ation arm compared with the PUVA-alone arm. The best overall response (CCR + PR) rate was 71% for PUVA alone and 77% for the combination arm (P =0Æ57). The med- ian duration of response was 9Æ7 months for PUVA vs. 5Æ8 months for the combination arm (P =0Æ33). CCR was seen in 25 patients of whom 10 received PUVA alone (CCR 22%) and 15 received combination therapy (CCR 31%) (P =0Æ45). CCR was sustained in 25% of patients regardless of therapy. There was a trend towards fewer PUVA sessions needed to achieve CCR in the combination arm (median 22) compared with the PUVA arm (median 27Æ5) (P =0Æ11). Similarly, a trend towards lower UVA dose required to achieve CCR in the combination arm (median 55Æ8 J cm )2 ) compared with the PUVA arm alone (median 117Æ5 J cm )2 )(P =0Æ5) was observed. Conclusions No significant difference in response rate or response duration was observed in this study. However, there was a trend towards fewer PUVA sessions and lower UVA dose required to achieve CCR in the combination arm (PUVA + bexarotene) but this did not achieve statistical significance due to insufficient power. Ó 2012 The Authors 678 BJD Ó 2012 British Association of Dermatologists 2012 167, pp678–687