Double blind randomized prospective trial of bethanechol in the prevention of radiation-induced salivary gland dysfunction in head and neck cancer patients Graziella Chagas Jaguar a , Eduardo Nóbrega Pereira Lima b , Luiz Paulo Kowalski c , Antônio Cássio Pellizzon d , André Lopes Carvalho e , Karina Waiswol Boccaletti d , Fabio Abreu Alves a,⇑ a Stomatology Department; b Nuclear Medicine Department; c Head and Neck Department; d Radiotherapy Department, A.C. Camargo Cancer Center; and e Head and Neck Department, Hospital do Câncer de Barretos, São Paulo, Brazil article info Article history: Received 2 October 2014 Received in revised form 16 March 2015 Accepted 16 March 2015 Available online xxxx Keywords: Xerostomia Bethanechol Salivary glands scintigraphy Salivary flow Intensity modulated radiation therapy Three-dimensional radiotherapy abstract This study assessed the prophylactic bethanechol use to prevent salivary gland dysfunction during radio- therapy. A total of 97 head and neck cancer patients were allocated into two groups: Bethanechol or Placebo. Bethanechol group presented significantly improve of salivary parameters. Bethanechol was effective in decreasing the salivary gland damage. Ó 2015 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology xxx (2015) xxx–xxx Radiation-induced hyposalivation and consequent xerostomia are the most common and disturbing side effects after radiation therapy for head and neck cancer (HNC). These complications sig- nificantly increase the risk of oral and dental diseases [1,2]. Several strategies such as amifostine [3], intensity-modulated radiother- apy – IMRT [2], surgical salivary gland transfer [4] and concomitant systemic sialogogues [5–10] have been used to combat med- ication-induced xerostomia. Previous studies have suggested that pilocarpine administration during radiotherapy (RT) prevent sali- vary gland dysfunction with significant subjective reduction in xer- ostomia because of its ability to promote functional stimulation of the salivary gland [5,6,9,10]. However, the prophylactic use of pilo- carpine is still controversial because of its toxic side effects [10,11]. In addition, few publications have documented the evidence that bethanechol may be useful in decreasing the incidence and/or severity of xerostomia with minimal side effects [8,11,12]. Hence, this study evaluated the bethanechol effect in a prospec- tive double blind setting in order to reduce or ameliorate xerosto- mia and hyposalivation. In addition, with the improvement of salivary flow, it would be expected a satisfactory condition of speaking, chewing, and swallowing, resulting in better quality of life. The objectives of this trial were (1) to evaluate the efficacy of the prophylactic use of bethanechol on reducing the xerostomia complain on head and neck irradiated patients through observer- assessed toxicity grading, (2) to verify its influence on salivary flow using sialometry, and (3) to determine its benefits on salivary gland function based on salivary gland scintigraphy. In addition, the safety of this drug was also assessed. Methods This was a prospective, double-blinded, randomized controlled trial which enrolled patients diagnosed with primary oral, orophar- ynx or nasopharynx carcinomas and were scheduled to undergo Three-dimensional radiotherapy (RTC3D) or Intensity modulated radiation therapy (IMRT). Radiation consisted of once-daily mega- voltage (6 MV), given at 1.8–2.12 Gy per fraction, 5 days per week. Both parotid and submandibular glands were contoured using anatomical atlas and corresponding dose in the irradiated volumes of 25%, 50%, 75% and 100% of each gland was acquired using a dose–volume histogram (DVH). Bethanechol and placebo were administered one tablet (25 mg tablets) taken twice a day from the beginning of RT and continued until 1 month after the end of treatment. http://dx.doi.org/10.1016/j.radonc.2015.03.017 0167-8140/Ó 2015 Elsevier Ireland Ltd. All rights reserved. ⇑ Corresponding author at: Departamento de Estomatologia, A.C. Camargo Cancer Center, R: Prof. Antônio Prudente, 211 Bairro: Liberdade, São Paulo CEP: 01509-900, SP, Brazil. E-mail address: falves@accamargo.org.br (F.A. Alves). Radiotherapy and Oncology xxx (2015) xxx–xxx Contents lists available at ScienceDirect Radiotherapy and Oncology journal homepage: www.thegreenjournal.com Please cite this article in press as: Jaguar GC et al. Double blind randomized prospective trial of bethanechol in the prevention of radiation-induced salivary gland dysfunction in head and neck cancer patients. Radiother Oncol (2015), http://dx.doi.org/10.1016/j.radonc.2015.03.017