No conventional therapy exists for salivary hypofunction in surviving head and neck cancer patients with Radiation Therapy Oncology Group late grade 2-3 toxicity. We conducted a phase I clinical trial to test the safety and biologic efficacy of serotype 5, adenoviral-mediated aquaporin-1 cDNA transfer to a single previously irradiated parotid gland in 11 subjects using an open label, single-dose, dose-escalation design (AdhAQP1 vector; four dose tiers from 4.8 × 10 7 to 5.8 × 10 9 vector particles per gland). Treated subjects were followed at scheduled intervals. Multiple safety parameters were measured and biologic efficacy was evaluated with measurements of parotid salivary flow rate. Symptoms were assessed with a visual analog scale. All subjects tolerated vector delivery and study procedures well over the 42-d study period reported. No deaths, serious adverse events, or dose-limiting toxicities occurred. Generally, few adverse events occurred, and all were considered mild or moderate. No consistent changes were found in any clinical chemistry and hematology parameters measured. Objective responses were seen in six subjects, all at doses <5.8 × 10 9 vector particles per gland. Five of these six subjects also experienced subjective improvement in xerostomia. AdhAQP1 vector delivery to a single parotid gland was safe and transfer of the hAQP1 cDNA increased parotid flow and relieved symptoms in a subset of subjects.gene therapy | radiation damage | salivary glands | dry mouth | water channel
Background
No standard oral assessment tools are available for determining frequency of oral care in critical care patients, and the method of providing oral care is controversial.
Objectives
To examine the effects of a systematic program of oral care on oral assessment scores in critically ill intubated and nonintubated, patients.
Methods
Clinical data were collected 3 times during critical care admissions before and after institution of a systematic program of oral care in 3 different medical centers. The oral care education program consisted of instruction from a dentist or dental hygienist and a clear procedure outlining systematic oral care. The Beck Oral Assessment Scale and the mucosal-plaque score were used to assess the oral cavity. Data were analyzed by using linear mixed modeling with controls for severity of illness.
Results
Scores on the Beck Scale differed significantly (F = 4.79, P = .01) in the pattern of scores across the 3 days and between the control group (before oral education) and the systematic oral care group. Unlike the control group, the treatment group had decreasing scores on the Beck Scale from day 1 to day 5. The mucosal-plaque score and the Beck Scale scores had strong correlations throughout the study; the highest correlation was on day 5 (r = 0.798, P < .001, n = 43).
Conclusions
Oral assessment scores improved after nurses implemented a protocol for systematic oral care. Use of the Beck Scale and the mucosal-plaque score could standardize oral assessment and guide nurses in providing oral interventions.
Longitudinal changes in serum HGF, IL-6, IL-8, and VEGF were detected with treatment response, relapse, or complications in individual patients and were associated with survival, with HGF showing the strongest relationship with survival. HGF, IL-6, IL-8, and VEGF merit investigation as markers of response, survival, and recurrence in larger prospective studies.
A significant long-term side effect of radiation therapy for head and neck cancers is xerostomia, a dry mouth, due to salivary gland damage. Despite continuing efforts to eliminate this problem, many patients continue to suffer. This brief review describes our efforts to develop a gene transfer approach, employing the aquaporin-1 cDNA, to treat patients with existing radiation-induced salivary hypofunction. A Phase I/II clinical trial, using a recombinant adenoviral vector to mediate gene transfer, is currently underway.
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