title: An Open-Label Phase II Randomized Trial of Topical Dexamethasone and Tacrolimus Solutions for the Treatment of Oral Chronic Graft-versus-Host Disease.
abstract: The objective of this study was to evaluate the safety and efficacy of single-agent dexamethasone or tacrolimus topical solution as first-line treatment for symptomatic oral chronic graft-versus-host disease (cGVHD). This was a prospective, single-center, open-label, randomized phase II trial of patients with symptomatic oral cGVHD without prior topical therapy. Subjects were randomly assigned 1:1 to either topical dexamethasone (.5 mg/mL) or tacrolimus (.5 mg/mL) solution and instructed to rinse with 5 mL for 5 minutes, 4 times a day, for 4 weeks. Oral cGVHD assessments (National Institutes of Health [NIH] criteria) were completed at baseline and end of treatment (NIH criteria, global response, and tolerability). The primary endpoint was the response rate defined as ≥3-point reduction in patient-reported sensitivity score (range, 0 to 10). A parallel 2-stage design was employed so that a less efficacious arm could be terminated early. The accrual goal was 60 evaluable patients; 30 in each arm), accruing 14 in the first stage and 16 in the second stage. If both arms were regarded as efficacious, a "pick-the-winner" method would be employed to choose a better treatment for future investigation. Forty-six subjects were randomized to receive either dexamethasone (n = 28) or tacrolimus (n = 18). Six subjects were excluded from the analysis because of changes in systemic immunosuppression (dexamethasone  = 1, tacrolimus  = 3) or lack of end-of-treatment visit (1 per arm). After the first stage evaluation, the tacrolimus arm was terminated because of lack of activity (3 of 14 responses; response rate, 21%). Twenty-six subjects in the dexamethasone arm completed both study visits and were included in the response analysis, with a 58% (15 of 26) response rate, compared with 21% (3 of 14) in the tacrolimus arm (P = .05). The response rates according to the NIH score in the dexamethasone and tacrolimus arms were 50% (13 of 26) and 2% (2 of 14), respectively (P = .04). From the onset of therapy, 31% versus 21% patients reported feeling "much better" and 38% versus 36% reported feeling "slightly better," giving an overall global response rate ("much better" or "slightly better") of 81% (21 of 26) versus 71% (10 of 14), in the dexamethasone and tacrolimus arms, respectively. Dexamethasone rinses were well tolerated and taste was reported as "very pleasant" or "tolerable" in most subjects (96%). Intensive topical therapy with dexamethasone solution is effective for managing patients with new-onset symptomatic oral cGVHD and should be considered for first-line therapy. Topical tacrolimus solution appears less effective, at least for first-line therapy.
authors: Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, Boston, Massachusetts; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts. Electronic address: ntreister@partners.org.
authors: Nathaniel
authors: N
authors: Treister
authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Shuli
authors: S
authors: Li
authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Haesook
authors: H
authors: Kim
authors: Department of Diagnostic Sciences, Tufts University School of Dental Medicine, Boston, Massachusetts.
authors: Mark
authors: M
authors: Lerman
authors: Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, Boston, Massachusetts; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts.
authors: Ahmed
authors: A
authors: Sultan
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Edwin P
authors: EP
authors: Alyea
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Philippe
authors: P
authors: Armand
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Corey
authors: C
authors: Cutler
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Vincent
authors: V
authors: Ho
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: John
authors: J
authors: Koreth
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Joseph H
authors: JH
authors: Antin
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Robert
authors: R
authors: Soiffer
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000008:administration & dosage*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D009059:Mouth Diseases / Q000188:drug therapy; D013280:Stomatitis / Q000188:drug therapy; D016559:Tacrolimus / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003907:Dexamethasone; D016559:Tacrolimus
keywords: Ancillary care; Chronic graft-versus-host disease (GVHD); Oral chronic GVHD; Oral medicine; Supportive care