Gerald A. Ferretti

Oral Pilocarpine for Post-Irradiation Xerostomia in Patients with Head and Neck Cancer

BACKGROUND AND METHODS We evaluated pilocarpine hydrochloride for the treatment of radiation-induced xerostomia, a common complication of irradiation of the head and neck. A prospective, randomized, double-blind, placebo-controlled trial was undertaken to test the safety and efficacy of pilocarpine, particularly in reversing the decrease in the production of saliva and other manifestations of xerostomia. Patients received either placebo or pilocarpine (5 mg or 10 mg orally three times a day) for 12 weeks and were evaluated at base line and every 4 weeks. RESULTS We studied 207 patients who had each received > or = 4000 cGy of radiation to the head and neck. In the patients receiving the 5-mg dose of pilocarpine, oral dryness improved in 44 percent, as compared with 25 percent of the patients receiving placebo (P = 0.027). There was overall improvement in 54 percent of the 5-mg group as compared with 25 percent of the placebo group (P = 0.003), and 31 percent of the 5-mg group had improved comfort of the mouth and tongue, as compared with 10 percent of the placebo group (P = 0.002). Speaking ability improved in 33 percent of the 5-mg group as compared with 18 percent of the placebo group (P = 0.037). Saliva production was improved, but it did not correlate with symptomatic relief. There were comparable improvements in the group receiving the 10-mg dose. The primary adverse effect was sweating, in addition to other minor cholinergic effects. Six and 29 percent of the patients in the 5-mg and 10-mg groups, respectively, withdrew from the study because of adverse effects. There were no serious adverse effects related to pilocarpine. CONCLUSIONS Pilocarpine improved saliva production and relieved symptoms of xerostomia after irradiation for cancer of the head and neck, with minor side effects that were predominantly limited to sweating.

Chlorhexidine prophylaxis for chemotherapy-and radiotherapy-induced stomatitis: A randomized double-blind trial

Patients receiving cytotoxic antineoplastic therapy often have treatment-associated stomatitis. A 0.12% chlorhexidine digluconate mouthrinse was evaluated (15 ml, three times a day) in a prospective, double-blind randomized trial as prophylaxis against cytotoxic therapy-induced damage to oral soft tissues. Seventy subjects, forty inpatients receiving high-dose chemotherapy and thirty outpatients receiving high-dose head and neck radiation therapy, were evaluated. Chlorhexidine mouthrinse significantly reduced the incidence of oral mucositis in the chemotherapy group on day 14 (p less than 0.02) and at 1 week follow-up on day 28 (p less than 0.002). Mucositis in the patients undergoing chemotherapy who received chlorhexidine also resolved more rapidly. Mucositis severity was significantly less compared to the control chemotherapy group on day 14 (p less than 0.03), day 21 (p less than 0.04), and on 1 week follow-up (p less than 0.02). Concomitant trends in the reduction in oral streptococci and yeast were noted in the chemotherapy group receiving chlorhexidine mouthrinse. Although no differences were observed in oral mucositis between the control and chlorhexidine groups of patients undergoing high-dose radiotherapy, similar reductions of oral microflora to those seen in the chemotherapy population were also noted for patients undergoing radiation therapy who received chlorhexidine. Although generally not significant, some increase in gram-negative bacilli was noted in the chlorhexidine-treated patients in both the chemotherapy and radiotherapy groups, but there was no correlation with increased systemic infection. Prophylactic chlorhexidine mouthrinse reduces oral mucositis and microbial burden in patients with cancer undergoing intensive chemotherapy.

Therapeutic use of chlorhexidine in bone marrow transplant patients: Case studies

Patients undergoing cytotoxic chemotherapy and radiation therapy often experience severe oral complications during and after treatment despite supervised oral hygiene and conventional antimicrobial regimens. The antimicrobial compound chlorhexidine is an effective topical prophylactic agent against oral mucositis and candidiasis. Oral mucositis developed in four patients who underwent bone marrow transplantation; the condition was severe enough to prompt use of chlorhexidine. In each case, there was clinical resolution of mucositis and a concomitant decrease in the oral microbial burden 1 week after chlorhexidine use began. This strongly suggests that, in addition to its value in protecting these severely immunocompromised patients from oral infection, chlorhexidine also offers a therapeutic benefit in the resolution of existing oral infections and of mucositis.

Clinical evaluation of MGI 209, an anesthetic, film-forming agent for relief from painful oral ulcers associated with chemotherapy.

PURPOSE This open-label, multicenter trial evaluated the efficacy of a mucoadherent, anesthetic medication (MGI 209) for relief from painful oral ulcers associated with cytotoxic chemotherapy. PATIENTS AND METHODS Twenty-eight eligible cancer patients who had up to five discrete oral ulcers (total area < or = 5 cm2) completed this study. Mean age was 53.5 years (range, 21 to 81). Subjective assessments of oral discomfort before and after an orange juice pain challenge (OJPC), which was measured using a visual analog scale (VAS), and visual estimates of the amount of MGI 209 that remained on treated ulcers were collected at (1) baseline (before MGI 209 treatment); and (2) 30, 60, 120, and 180 minutes posttreatment. RESULTS Most subjects had low VAS scores (4 or less), which was indicative of oral discomfort, at baseline before and after the OJPC. At 30, 60, 120, and 180 minutes after MGI 209 treatment, most subjects had high VAS scores before and after an OJPC compared with baseline scores, which was indicative of a substantial increase in oral comfort; these differences were statistically significant (P < .0001). Mean percent of MGI 209 estimated to remain on ulcers at the previously mentioned times was 93.7%, 90.3%, 79.6%, and 71.3% of the total amount applied, respectively. CONCLUSION Benzocaine hydrochloride in combination with the protective, mucoadherent film-coating relieved discomfort for at least 3 hours even with exposure to an irritating beverage. MGI 209 treatment should allow patients with chemotherapy-induced oral ulcers to drink and eat with significantly diminished pain or no pain.

OralCandida albicans in bone marrow transplant patients given chlorhexidine rinses: Occurrence and susceptibilities to the agent

The tongue and buccal mucosa of 26 bone marrow transplant recipients given three 0.12% chlorhexidine digluconate (CHX) oral rinses daily for 8 weeks were sampled weekly for oral Candida albicans. Putative C. albicans colony-forming units on selective bismuth sulfite glucose glycine yeast agar plates were identified with the API 20C system. The CHX minimum inhibitory concentrations (MICs) of oral C. albicans isolates obtained at all 8 sample weeks was determined with a microbroth dilution sensitivity assay. The CHX MIC range for yeast isolates selected randomly at all sample weeks was up to 2.5 to up to 20 micrograms/ml (mean MIC less than or equal to 8.5 micrograms/ml). The CHX MIC range for isolates at week 1 was less than or equal to 5 to less than or equal to 10 micrograms/ml (mean MIC less than or equal to 7.9 micrograms/ml) compared with less than or equal to 2.5 to less than or equal to 20 micrograms/ml at week 8 (mean MIC less than or equal to 8.8 micrograms/ml). Therefore the persistence of oral C. albicans in bone marrow transplant recipients using CHX rinses was due neither to low CHX susceptibilities nor to the development of resistance to the agent.

Dentinal candidiasis in cancer patients.

Two examples of an unusual presentation of oropharyngeal candidiasis in cancer patients are offered. The light and scanning electron microscopic appearances of candidiasis involving the dentin of teeth are described. The potential significance of recognition of this form of candidiasis in cancer patients is discussed.

In vitro effect of chlorhexidine and amikacin on oral gram-negative bacilli from bone marrow transplant recipients.

Prophylactic use of chlorhexidine (CHX) mouthrinses has been shown to benefit the oral health status of bone marrow transplant recipients and other immunosuppressed persons and to reduce systemic complications of oral origin. However, a problem that often emerges with these patients is oropharyngeal and lower respiratory tract colonization by opportunistic aerobic or facultative gram-negative bacilli (GNB). Trends in four studies indicated that CHX rinses may predispose these persons to oral colonization by GNB such as the enterobacteria, Klebsiella pneumoniae and Enterobacter cloacae. Since GNB are generally susceptible to broad-spectrum aminoglycoside antibiotics such as amikacin, the in vitro sensitivities of K. pneumoniae, E. cloacae, Pseudomonas aeruginosa, and Escherichia coli ATCC reference strains and K. pneumoniae and E. cloacae oral clinical isolates to combinations of CHX and amikacin were determined by means of a disk diffusion sensitivity assay on Mueller-Hinton agar. The amikacin minimum inhibitory concentrations for all GNB tested were much lower (less than or equal to 4.69 to less than or equal to 9.37 micrograms/ml) than those for CHX (less than or equal to 18.75 to less than or equal to 300 micrograms/ml), and combinations of CHX and amikacin gave larger growth inhibition zones than CHX alone. No antibacterial antagonism between CHX and amikacin was found, and their solubilities were compatible. Therefore use of topical amikacin in conjunction with CHX rinses may reduce oral colonization by GNB in severely immunocompromised patient populations.

Oral Gram-negative Bacilli in Bone Marrow Transplant Patients Given Chlorhexidine Rinses

Fifteen bone marrow transplant (BMT) patients who received three 0.12% chlorhexidine digluconate (CHX) mouthrinses daily for eight weeks were monitored weekly for the occurrence of oral opportunistic Gram-negative bacilli (GNB). Tongue and buccal mucosa were sampled with use of Culturette swabs that were streaked on plates containing selective MacConkey agar. After incubation, colony-forming units were scored and putative GNB classified with use of the API 20E rapid identification system and supplemental biochemical tests. After identification, the susceptibilities of all GNB to CHX were determined by means of a disk diffusion sensitivity assay. Sixty-seven percent (10) of the BMT subjects had at least one GNB-positive tongue culture, and 53% (8) had GNB in samples taken from the buccal mucosa. Of 218 samples taken, 26% and 24% from the tongue and buccal mucosa, respectively, were GNB-positive. The predominant clinical GNB isolates were Enterobacter cloacae (46%) and Klebsiella pneumoniac (30%). Their respective CHX minimum inhibitory concentrations (MICs) were similar to those of ATCC reference strains. Although the CHX MIC values of the clinical GNB isolates were high (≤37.5 to ≤300 μg/mL), they were not dependent upon length of exposure to the agent. Therefore, changes in sensitivity or resistance to CHX did not appear to occur. The results suggest that the mouths of BMT patients - and perhaps of other immunosuppressed individuals - should be routinely monitored for GNB, as are other clinically important sites, such as the throat and the urinary and gastro-intestinal tracts.

Maintaining Oral Health

The prevention of dental disease plays a significant role in the comprehensive health care of children. This responsibility should be shared by the child, the parents, and the health care professional, and it is essential that programs be initiated early in life to incorporate the proper use of oral hygiene, fluoride, and appropriate dietary practice.