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).

Abstract

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 treated with PUVA alone or PUVA and bexarotene.

METHODS:

EORTC 21011 (NCT 00056056) was a randomized phase III study comparing combined bexarotene (Targretin(®) ) 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 1·4-489·9) in the PUVA arm vs. 101·7 J cm(-2) (0·2-529·9) 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 combination 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 = 0·57). The median duration of response was 9·7 months for PUVA vs. 5·8 months for the combination arm (P = 0·33). CCR was seen in 25 patients of whom 10 received PUVA alone (CCR 22%) and 15 received combination therapy (CCR 31%) (P = 0·45). 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 27·5) (P = 0·11). Similarly, a trend towards lower UVA dose required to achieve CCR in the combination arm (median 55·8 J cm(-2) ) compared with the PUVA arm alone (median 117·5 J cm(-2) ) (P = 0·5) 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.

• Authors: S Whittaker, P Ortiz, R Dummer, A Ranki, B Hasan, B Meulemans, S Gellrich, R Knobler, R Stadler, M Karrasch
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 167 Issue 3 Pg. 678-87 (Sep 2012) ISSN: 1365-2133 [Electronic] England
• PMID: 22924950 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

Chemical References

• Anticarcinogenic Agents
• Photosensitizing Agents
• Tetrahydronaphthalenes
• Bexarotene
• Methoxsalen

Topics

• Adolescent
• Adult
• Aged
• Anticarcinogenic Agents (administration & dosage, adverse effects)
• Bexarotene
• Child
• Child, Preschool
• Combined Modality Therapy (methods)
• Dose-Response Relationship, Drug
• Dose-Response Relationship, Radiation
• Early Termination of Clinical Trials
• Humans
• Infant
• Methoxsalen (administration & dosage, adverse effects)
• Middle Aged
• Mycosis Fungoides (drug therapy, pathology)
• PUVA Therapy (adverse effects, methods)
• Photosensitizing Agents (administration & dosage, adverse effects)
• Skin Neoplasms (pathology, therapy)
• Tetrahydronaphthalenes (administration & dosage, adverse effects)
• Treatment Outcome
• Young Adult