Trial Information

Evaluation of Efficacy and Mechanisms of an Anti-Inflammatory Intervention for Chemotherapy Related Mucosal Injury

Stomatitis is defined as inflammation of the mucous membranes of the oral cavity and
oropharynx characterized by tissue erythema, edema, and atrophy, often progressing to
ulceration. Stomatitis is a biologically complex, multifactorial, treatment-related oral
condition experienced by many oncology patients, which often leads to a cascade of negative
sequelae including oropharyngeal pain, critical treatment alterations or cessation, and
decreased quality of life. The optimal treatment strategies for stomatitis have not been
established. There is a critical need to examine the pathogenesis of and to evaluate
interventions for stomatitis and related acute oropharyngeal pain in the randomized
controlled clinical trial setting using valid and reliable stomatitis assessment tools to
both advance the science of cancer treatment-related oral toxicities and improve patient
care. Therefore, the purpose of this randomized controlled clinical trial is to elucidate
the role of inflammation in stomatitis by testing the effects of a novel tumor necrosis
factor (TNF) fusion protein etanercept, (Enbrel(Registered Trademark), Immunex Corporation,
Seattle, WA) on the incidence and severity of stomatitis. The actions of this fusion
protein, which binds specifically to TNF preventing its interaction with cellular receptors
and altering the inflammatory cascade, may provide insight into the role of inflammation in
stomatitis. An etanercept effect is defined as a prevention or amelioration of stomatitis
and acute oropharyngeal pain and/or changes in levels of tissue mediators. If stomatitis is
primarily a consequence of a mucosal inflammatory response, then we hypothesize that this
oral condition will be responsive to binding of TNFa. Elaboration of the role of
inflammatory cell signaling associated with stomatitis and the effect of TNFa may elucidate
the mechanisms related to the pathogenesis of stomatitis and to other mucosal conditions.

Patients who are scheduled to receive autologous or allogeneic peripheral blood stem cell or
bone marrow transplant will be invited to participate in this study during a regularly
scheduled pre-treatment visit. Written informed consent will be obtained from all
participants. Patients will be randomized to receive either etanercept mouthwash or placebo,
which will both be administered by protocol schedule. Stomatitis and oropharyngeal pain will
be measured at baseline and at specified post-chemotherapy time points corresponding with
the predicted stomatitis onset, peak, and healing time course. TNFa levels in buccal mucosa,
analyzed by reverse transcriptase polymerase chain reaction techniques, and blood levels of
pro-inflammatory cytokines, growth factors, and inflammatory mediators will also be measured
at baseline and at specified post-chemotherapy time points corresponding with the predicted
stomatitis onset, peak, and healing time course.