Evaluating a PBMT–pilocarpine combination to improve salivary gland function during radiochemotherapy in head and neck cancer: an exploratory randomized trial

Abstract Hyposalivation is a frequent and disabling complication in head and neck cancer (HNC) patients undergoing radiochemotherapy (RCT), with few effective long-term interventions currently available. This randomized prospective study evaluated the preliminary clinical outcomes of a combined intervention involving photobiomodulation therapy (PBMT) and pilocarpine hydrochloride in mitigating RCT-induced hyposalivation and disruptions in salivary electrolyte balance. Twenty-four HNC patients undergoing RCT were randomized into three groups: Pilocarpine alone, PBMT alone, and a combined PBMT–Pilocarpine regimen. Salivary flow rates (stimulated and unstimulated), pH, and concentrations of sodium, potassium, chloride, and calcium in unstimulated saliva were assessed at baseline (R1), end of RCT (R2), and 3-month follow-up (R3). Statistical analyses were performed using appropriate parametric and non-parametric methods. Unstimulated salivary flow remained largely unchanged across groups. For stimulated salivary flow (SSF), no statistically significant difference was observed in the primary endpoint (R1 to R3 comparison). However, in an exploratory secondary analysis, the combined group demonstrated a statistically significant increase between R2 and R3, whereas declines were observed in the PBMT and pilocarpine groups. The between-group difference in change from R2 to R3 favored the combined group (mean difference vs. PBMT: 0.33 mL/min, 95% CI [0.07–0.59]). Electrolyte concentrations increased at R2 across all groups and showed partial normalization by R3, with trends favoring the combined group. In conclusion, the combined approach may be associated with more favorable salivary outcomes during radiochemotherapy. However, given the small sample size, these findings should be considered exploratory and hypothesis-generating and require confirmation in larger studies. Trial Registration: This clinical trial was registered with the ISRCTN registry (ISRCTN56133161) on August 21, 2023.