Use of pilocarpine during head and neck radiation therapy to reduce xerostomia and salivary dysfunction

Abstract

Background. Salivary gland hypofunction commonly develops during radiation therapy to the head and neck region. This study evaluated whether the sialogogue pilocarpine given during radiation therapy may reduce the severity of xerostomia and salivary dysfunction. Methods. Nine patients requiring head, neck, or mantle radiation therapy participated in this double‐blind, placebo‐controlled trial. The patients took either 5 mg of pilocarpine or placebo four times daily for 3 months, beginning the day before radiation therapy. Subjective complaints and salivary functions were assessed. Results. The pilocarpine‐treated group had a lower frequency of oral symptoms during treatment than the placebo‐treated group. Although salivary flow decreased in all patients, the pilocarpine‐treated group had smaller reductions in flow. No drug effect was observed in glands that were irradiated completely. Thus, pilocarpine appeared to stimulate salivary tissues outside the radiation field. Conclusions. These results suggest that stimulation with pilocarpine may reduce the severity of salivary dysfunction and associated oral symptoms during radiation therapy.

A Comparative Study on the Protection Profile of Lidocaine, Amifostine, and Pilocarpin on the Parotid Gland during Radiotherapy

“…A single clinical trial on a further protection of radiogenic sialadenitis and mucositis by coumarin/troxerutine was also reported by Grotz et al (10). Among the so-called preemptive drugs, pilocarpin has gained ground, not only in experimental studies (11) but in clinical trials as well (12,13). Postulating the hypothesis of basolateral membrane damage as an initial target site of radiation, Stephens et al (14) suggested a further prophylactic approach, which has been proven to reduce this damage in cell culture, namely the membrane stabilization agent lidocaine.…”

Clinical features and preventive therapies of radiation-induced xerostomia in head and neck cancer patient: a literature review

“…The study conducted by Valdez et al [28] was the first randomized double blind clinical trial that evaluated the use of pilocarpine during the course of RT. A total of 9 patients with HNC took either pilocarpine or placebo four times daily for 3 months, beginning the day before RT.…”

“…The prophylactic use of systemic sialogogues for radiationinduced xerostomia is widely reported in the literature [28][29][30][31][32][33][34][35][36]. These drugs are defined as systemic stimulants of salivary gland function by acting directly on the parasympathetic nervous system [19].…”

“…Pilocarpine hydrochloride is the most widely studied sialogogue in the literature [28,29,31,34,35]. It is defined as a cholinergic parasympathomimetic agent with action on muscarinic and α/β -adrenergic receptors [17,38].…”

“…Some authors state that it is pharmacological mediator, with pilocarpine being able to cause depletion of secretory granules in serous cells and consequently decrease radiation-induced salivary damage [17,28,29]. Others postulated that pre-treatment with pilocarpine leads to an activation of intracellular signaling pathways [20].…”