Preventive intraglandular botulinum toxin type A for radiation‑induced salivary gland dysfunction in head and neck squamous cell carcinoma patients

The primary objective is to determine whether intraglandular administration of botulinum toxin type A before radiotherapy preserves salivary gland function in patients with head and neck squamous cell carcinoma, addressing the clinical need to mitigate radiation‑induced xerostomia.

Secondary objectives include:

• Assessment of quantitative salivary secretion following treatment.
• Evaluation of patient‑reported xerostomia and health‑related quality of life.
• Investigation of safety and tolerability of the intraglandular injection.

The trial enrolled adult patients (≥ 18 years) of both sexes with a diagnosis of head and neck squamous cell carcinoma who were scheduled to receive radiotherapy and demonstrated symmetrical submandibular gland function on pre‑treatment Tc99m scintigraphy; all participants provided signed informed consent. Selection was based on histologic confirmation of the malignancy and eligibility for radiotherapy, without additional lifestyle restrictions reported. The sponsor did not provide information on the total number of participants enrolled in the study.

The trial is a Phase 4, Category 2 interventional study evaluating intraglandular administration of botulinum toxin type A before radiotherapy in adults with head and neck squamous cell carcinoma. Participants undergo a screening visit, a baseline visit for a single 2 ml injection of BOTOX 100 units, standard radiotherapy, and scheduled follow‑up assessments at the end of radiotherapy, and at 3, 6 and 12 months post‑treatment, concluding with an end‑of‑study visit at 12 months. The primary endpoint is the change in salivary gland function assessed by dynamic Tc99m scintigraphy; secondary endpoints include quantitative salivary flow, ultrasound gland parameters, xerostomia questionnaire scores, quality‑of‑life measures, and safety evaluations. Participant involvement therefore lasts approximately 12 months from baseline injection to study completion. Early termination may occur if a participant withdraws consent, experiences a serious adverse event related to the investigational product, shows disease progression that precludes continued radiotherapy, or breaches major protocol criteria.

The investigational product is botulinum toxin type A supplied as BOTOX 100 units defined by Allergan, a powder for injection reconstituted to a solution for injection. The preparation is administered intraglandularly as a 2 ml dose of the solution, delivered by injection into the salivary glands prior to the initiation of radiotherapy. The administration is performed once, on the day designated for pre‑radiotherapy treatment, and is carried out by qualified clinical staff under aseptic conditions.

All participants receive standard radiotherapy for head and neck cancer in accordance with institutional protocols. Radiotherapy constitutes the non‑experimental comparator and is delivered according to the prescribed schedule for each patient’s disease stage and treatment plan. No placebo injection is employed; the study compares the effect of the single intraglandular injection of the investigational product against the standard radiotherapy regimen alone.

Compliance with the investigational product administration is verified by direct observation of the injection procedure and documentation of the administered volume. Timing of the injection relative to the radiotherapy start date is recorded to ensure adherence to the protocol‑specified schedule.

The primary efficacy assessment will be the change in salivary gland function measured by dynamic Tc99m scintigraphy (excretory fraction), with values obtained before radiotherapy and after completion of radiotherapy to evaluate the biomarker of gland function.

Secondary efficacy evaluations will include quantitative changes in salivary secretion obtained using Škach’s test for both stimulated and unstimulated flow, structural alterations of the salivary glands assessed by ultrasound (gland volume and echostructure), patient‑reported xerostomia measured with the Xerostomia Questionnaire (XQ), and overall quality of life evaluated by the EORTC QLQ‑C30. Safety and tolerability will be monitored through the incidence and severity of adverse events (CTCAE grading) and the occurrence of local injection‑site complications.