Randomized placebo-controlled phase II trial of high-dose melatonin mucoadhesive oral gel for the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing radiation therapy concurrent with systemic treatment.

PURPOSE: The objective of this trial was to evaluate the safety and efficacy of melatonin oral gel mouthwashes in the prevention and treatment of oral mucositis (OM) in patients treated with concurrent radiation and systemic treatment for head and neck cancer. METHODS: Randomized, phase II, double-blind, placebo-controlled trial (1:1 ratio) of 3% melatonin oral gel mouthwashes vs. placebo, during IMRT (total dose ≥ 66 Gy) plus concurrent Q3W cisplatin or cetuximab. Primary endpoint: grade 3-4 OM or Severe Oral Mucositis (SOM) incidence by RTOG, NCI, and a composite RTOG-NCI scales. Secondary endpoints: SOM duration and grade 2-4 OM or Ulcerative Oral Mucositis (UOM) incidence and duration. RESULTS: Eighty-four patients were included in the study. Concurrent systemic treatments were cisplatin (n = 54; 64%) or cetuximab (n = 30; 36%). Compared with the placebo arm, RTOG-defined SOM incidence was numerically lower in the 3% melatonin oral gel arm (53 vs. 64%, P = 0.36). In patients treated with cisplatin, assessed by the RTOG-NCI composite scale, both SOM incidence (44 vs. 78%; P = 0.02) and median SOM duration (0 vs. 22 days; P = 0.022) were significantly reduced in the melatonin arm. Median UOM duration assessed by the RTOG-NCI scale was also significantly shorter in the melatonin arm (49 vs. 73 days; P = 0.014). Rate of adverse events and overall response rate were similar between the two arms. CONCLUSIONS: Treatment with melatonin oral gel showed a consistent trend to lower incidence and shorter SOM duration and shorter duration of UOM. These results warrant further investigation in phase III clinical trial.

Salvage irradiation of oral and oropharyngeal cancers using interstitial radiotherapy with au-198 grains.

Fourteen patients with recurrent or persistent carcinoma of the oral cavity or oropharynx were treated with Au-198 grain implants at the Santa Creu i Sant Pau Hospital from June 1987 through April 1991. Five patients presented recurrent carcinoma, four patients persistent carcinoma, and five patients a second primary. Local control was achieved with Au-198 implants in six patients (42.8%) at 8, 16, 23, 29, 39 and 53 months following treatment. Seven patients died of local recurrence or persistent disease at 5, 7, 7, 10, 10, 12 and 15 months after interstitial implant. Three patients (21.4%) died of significant complications of salvage irradiation (Hemorrhage in two patients and edema in one patient) at 0.5, 8 and 16 months following treatment. Three patients of fourteen (21.4%) are alive and well at 53, 39 and 23 months after salvage Au-198 grain implant. Considerations regarding the usefulness of Au-198 grain implants in the treatment of recurrent or persistent oral and oropharyngeal cancer are discussed.