Topical transforming growth factor-beta 3 in the prevention or alleviationof chemotherapy-induced oral mucositis in patients with lymphomas or solidtumors

Transforming growth factor (TGF)-beta3 has been hypothesized to prevent or alleviate oral mucositis (OM) in cancer patients receiving high-dose chemot herapy (CT). Two double-blind, placebo-controlled, multicenter, phase II St udies of TGF-beta3 were initiated in the United States, Europe, and Argenti na in patients with lymphomas or solid tumors who were receiving highly sto matotoxic CT regimens. Patients were to apply 10-mL mouthwash applications of TGF-beta3 (25 mug/mL) or placebo four times daily (or twice daily) I day before and all days during CT. The patients were subsequently evaluated fo r OM incidence, severity, and duration using National Institute of Cancer C ommon 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 a nalysis of the ongoing clinical trials. One hundred fifty-two patients from the combined studies were included ill the interim analysis, with 116 pati ents on the TGF-beta3 four times daily and placebo arms. Most (72%) patient s had breast cancer, 22% had lymphomas, and 6% had other solid tumors. Alth ough 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 rel evant differences were seen between the treatment and placebo arms regardin g safety, nor was there evidence for systemic absorption of TGF-beta3. Fina lly, there was no advantage of' TGF-beta3 treatment regarding the incidence (TGF-R3 four times daily versus placebo [46% versus 47%]), onset, or durat ion of NCI-CTC grade 3 or 4 OM. For this dose, formulation, regimen, and pa tient population, TGF-beta3 was not effective in the prevention or alleviat ion of CT-induced OM.