Topical Transforming Growth Factor-β3 in the Prevention or Alleviation of Chemotherapy-Induced Oral Mucositis in Patients with Lymphomas or Solid Tumors

Transforming growth factor (TGF)-β3 has been hypothesized to prevent or alleviate oral mucositis (OM) in cancer patients receiving high-dose chemotherapy (CT). Two double-blind, placebo-controlled, multicenter, phase II studies of TGF-β3 were initiated in the United States, Europe, and Argentina in patients with lymphomas or solid tumors who were receiving highly stomatotoxic CT regimens. Patients were to apply 10-mL mouthwash applications of TGF-β3 (25 μg/mL) or placebo four times daily (or twice daily) 1 day before and all days during CT. The patients were subsequently evaluated for OM incidence, severity, and duration using National Institute of Cancer Common Toxicity Criteria (NCI-CTC) criteria and an objective scoring system (1). After the start of the trials, negative results from new preclinical studies suggesting suboptimal formulation and/or dosing led to an interim analysis of the ongoing clinical trials. One hundred fifty-two patients from the combined studies were included in the interim analysis, with 116 patients on the TGF-β3 four times daily and placebo arms. Most (72%) patients had breast cancer, 22% had lymphomas, and 6% had other solid tumors. Although 98% (149 of 152) of patients experienced adverse events, only 14% (22 of 152) experienced events that were judged as possibly or probably related to the study drug (primarily gastrointestinal symptoms). No clinically relevant differences were seen between the treatment and placebo arms regarding safety, nor was there evidence for systemic absorption of TGF-β3. Finally, there was no advantage of TGF-β3 treatment regarding the incidence (TGF-β3 four times daily versus placebo [46% versus 47%]), onset, or duration of NCI-CTC grade 3 or 4 OM. For this dose, formulation, regimen, and patient population, TGF-β3 was not effective in the prevention or alleviation of CT-induced OM.