Duvic 2001.

Study characteristics
Methods	This was a randomised, open‐label, parallel‐group trial, which lasted 16 weeks.
Participants	The study recruited 58 participants (15 in the low‐dose group with 6.5 mg/m² daily versus 43 in the high‐dose group, which consisted of 28 participants who had 300 mg/m² daily and 15 participants who had 650 mg/m² daily) with histologically‐confirmed mycosis fungoides: CTCL stage I through IIA refractory to therapy; the participant was intolerant to therapy; or the participant had reached a 6‐month or greater response plateau under at least 2 of the following qualifying prior therapies: phototherapy (psoralen‐UVA or UVB), total body skin electron beam irradiation therapy, topical chemotherapy (mechlorethamine [nitrogen mustard] or carmustine therapy), or interferon, or systemic cytotoxic chemotherapy. Demographics of the included participants 40 men and 18 women Mean age (range) = 64 years (24 to 88 years) Stages of disease: IA: 17, IB: 34, IIA: 6, IIB: ? 142 participants (72.4%) were lost in total to follow‐up Exclusion criteria of the trial < 18 years Systemic antibiotic or topical therapy (for 2 weeks prior) Phototherapy (for 3 weeks prior) Systemic cancer therapy, electron beam, or other experimental therapy (for 30 days prior) Etretinate therapy (for 1 year prior) Other oral retinoid therapies (for 3 months prior)
Interventions	The low‐dose group received bexarotene 6.5 mg/m²/day capsules (10 mg or 75 mg) once daily with their evening meal. The high‐dose group received bexarotene 650 mg/m²/day (reduced to 500) mg/m²/day capsules (10 mg or 75 mg) once daily with their evening meal or bexarotene 300 mg/m²/day capsules (10 mg or 75 mg) once daily with their evening meal after adjusting the dose during the trial.
Outcomes	Outcomes of the trial Quality of life measured by the Spitzer quality of life questionnaire and a non‐validated CTCL quality of life questionnaire Common adverse effects of the treatments Percentage of participants demonstrating complete response Relapse defined as the time period after remission when the eruption reappears after short‐term clearance Overall survival (assessed 4 weeks after the end of the intervention) Objective response rate Rare adverse effects
Notes	The high‐dose was reduced twice (from 650 mg/m²/day to > 500 mg/m²/day, and from 500 mg/m²/day to > 300 mg/m²/day) during the trial; there was separate assessments of the high‐dose and "optimal" dose groups. 11/15 participants in the low‐dose group crossed over to high‐dose therapy after 8 weeks of treatment. Randomisation discontinued during the trial after interim analysis and was reinstalled after consideration by the U.S. Food and Drug Administration (FDA). The dropout rate for withdrawals was 72.4%. Dr Duvic was funded by research grants from Ligand Pharmaceuticals, San Diego California, USA (R21‐CA74117); from the National Institutes of Health, Bethesda, Maryland; and from the MD Anderson Cancer Centre (CA16672‐22). This study was conducted in 18 CTCL clinics at academic referral centres in the USA, Canada, Australia, and Europe.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	The study did not provide information about this. We sought information, but received no response.
Allocation concealment (selection bias)	Unclear risk	The study did not provide information about this. We sought information, but received no response.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "Blinding was not possible because of the number of capsules given."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The physician was blinded to CA response because it was calculated from the case report form."
Incomplete outcome data (attrition bias) All outcomes	High risk	The dropout rate for withdrawals was 72.4%. Reasons for dropout were withdrawal due to adverse effect, progressive disease, withdrawal of consent or patients being lost to follow‐up.
Selective reporting (reporting bias)	Unclear risk	This was unknown. We contacted the corresponding author for additional outcome data, but we received no reply within 4 weeks.
Other bias	High risk	The initial dose in the intervention group was reduced from 650 mg/m²/day to 500 mg/m²/day to 300 mg/m²/day due to adverse reactions. The study discontinued randomisation.