Ketoconazole and candidiasis: a controlled study. Ketoconazole in the prevention of candidiasis in patients with cancer. A prospective, randomized, controlled, double-blind study. Therapy for oropharyngeal candidiasis in the immunocompromised host: a randomized double-blind study of fluconazole vs. ketoconazole. Prophylaxis of candidiasis in cancer patients. Control of oral mucositis and candidiasis in marrow transplantation: a prospective, double-blind trial of chlorhexidine digluconate oral rinse. An open multicentre comparative study of the efficacy, safety and tolerance of fluconazole and itraconazole in the treatment of cancer patients with oropharyngeal candidiasis. Fluconazole versus nystatin in the prevention of candida infections in children and adolescents undergoing remission induction or consolidation chemotherapy for cancer. Controlled study of lactoperoxidase gel on oral flora and saliva in irradiated patients with oral cancer. Once-weekly fluconazole to prevent recurrence of oropharyngeal candidiasis in patients with AIDS and AIDS-related complex: a double-blind placebo-controlled study.
A double-blind, placebo-controlled study was undertaken to determine the efficacy of ketoconazole in the treatment of candidiasis. The drug was administered orally in the dosage of 200 mg/m2 of body surface per day for two weeks to cancer patients with oral candidiasis. Randomization in a 2:1 ratio provided 36 patients treated with ketoconazole and 20 managed with a placebo. Regression of visible lesions was achieved in 26 (72%) of 36 ketoconazole-treated and four (20%) of 20 untreated patients; eradication of culturable organisms occurred in 12 (36%) of 33 ketoconazole-treated and one (7%) of 14 untreated patients; and resolution of lesions plus eradication of Candida albicans occurred in nine (25%) of 36 ketoconazole-treated and one (5%) of 20 untreated patients. Although the therapeutic efficacy of ketoconazole was demonstrated for oropharyngeal candidiasis, the magnitude of its efficacy was less than that desired. A prospective, randomized, controlled, double-blind study was performed between 1982 and 1985 to assess the ability of ketoconazole to prevent fungal infections in selected patients with cancer. Fifty-six patients receiving induction chemotherapy for acute leukemia, autologous bone marrow transplant for refractory nonhematopoietic malignant neoplasms, multidrug chemotherapy for malignant lymphoma, or corticosteroids for brain metastases were randomized to receive either oral ketoconazole, 400 mg/d, or placebo and observed until leukopenia resolved or corticosteroid therapy was stopped. Oral candidiasis developed in eight (28%) of 29 patients receiving placebo compared with none of 27 receiving ketoconazole. However, ketoconazole failed to prevent Candida esophagitis and vulvovaginitis in two patients and one patient, respectively. Furthermore, prophylactic use of ketoconazole did not significantly alter the total number of hospital days, febrile days, or antibiotic days or the requirement for amphotericin B in patients with acute leukemia and autologous bone marrow transplant. Since oral candidiasis can be successfully managed by several different treatment modalities when it does occur, we do not think that the routine prophylactic use of ketoconazole is justified. Optimal therapy for oropharyngeal candidiasis, a common infection in immunocompromised patients, has yet to be clearly defined. Topical therapy is usually poorly tolerated; ketoconazole is effective but absorption is highly variable. New antifungal agents have been developed to increase the therapeutic options. Fluconazole is active against yeasts, is available in both oral and intravenous formulations, and has a pharmacokinetic profile different from that of ketoconazole. This randomized double-blind study evaluates systemic antifungal therapy with fluconazole (100 mg daily) or ketoconazole (400-mg daily) for oropharyngeal candidiasis in patients with cancer. Clinical cure was observed in 15 of 19 and 14 of 18 patients treated with fluconazole and ketoconazole, respectively. Eradication of pathogenic yeasts ws documented for 10 patients in both groups. The rates of relapse were similar, but relapse occurred earlier in patients in the ketoconazole group. Overall, this study demonstrates the value of a dosage of 100 mg of fluconazole or of 400 mg of ketoconazole daily for the management of oropharyngeal candidiasis in patients with cancer. Patients undergoing therapy for metastatic malignancies were randomly assigned to receive fluconazole or placebo as antifungal prophylaxis. Oropharyngeal candidiasis developed in 28% of 54 evaluable patients receiving placebo but in only 2% of 58 evaluable patients receiving fluconazole (P = .0003). Among patients receiving placebo, oropharyngeal candidiasis (thrush) occurred in 30% of those receiving antibiotic therapy and in 44% of those receiving adrenal corticosteroid therapy. Oropharyngeal candidiasis developed in 54% of the placebo patients who were colonized by Candida sp at the onset of prophylaxis. Fluconazole proved to be effective for prophylaxis of oropharyngeal candidiasis in susceptible patients and was well tolerated. Conditioning chemoradiotherapy damages the mucosal barrier of the mouth and throat and often produces severe oral inflammation and infection. In a prospective, double-blind, randomized study, we examined the use of a chlorhexidine digluconate mouthrinse for prophylaxis against oral mucosal complications in 51 bone marrow transplant patients. Use of chlorhexidine mouthrinse produced significant reductions in the incidence and severity of oral mucositis. Mucositis also resolved more quickly in patients receiving chlorhexidine. Concomitant reductions in total oral streptococci (p less than 0.02-p less than 0.001) and oral candida (p less than 0.004) were seen in patients using chlorhexidine. Persistent clinical oral candidiasis (thrush) was observed in 15 to 27 control group patients (56%), but only transiently in two (8%) of 24 patients who used chlorhexidine rinse (p less than 0.001). Five of 27 control group patients (19%) had candidemia, while no candidemia was observed in the chlorhexidine group (p less than 0.03). Three deaths from disseminated candidiasis occurred in the placebo group; none occurred in patients who received chlorhexidine. Prophylactic use of chlorhexidine mouthrinse produces reductions in oral soft tissue disease and oral microbial burden in patients undergoing bone marrow transplantation. The reductions in mucositis and in oral candida infections observed with prophylactic chlorhexidine mouthrinse represent a significant advantage for patients undergoing marrow transplantation. Oropharyngeal candidiasis is a frequent infection in cancer patients who receive cytotoxic drugs. In this study, the efficacy, safety and tolerance of fluconazole and itraconazole were compared in non-neutropenic cancer patients with oropharyngeal candidiasis. Of 279 patients who were randomised between the two treatment groups, 252 patients were considered to be eligible (126 in each group). The clinical cure rate was 74% for fluconazole and 62% for itraconazole (P=0.04, 95% Confidence Interval (CI): 0.5-23.3%). The mycological cure rate was 80% for fluconazole and 68% for itraconazole (P=0.03, 95% CI: 1.2-22.6%). The safety and tolerance profile of both drugs were comparable. This study has shown that in patients with cancer and oropharyngeal candidiasis, fluconazole has a significantly better clinical and mycological cure rate compared with itraconazole. An open, prospective, randomized pilot study was performed to assess the efficacy and safety of oral fluconazole 3 mg/kg once daily compared with oral nystatin 50,000 units/kg/day in four divided doses in preventing candida infections in 50 children undergoing remission induction or consolidation therapy for cancer. In 21 of 25 fluconazole-treated and 20 of 25 nystatin-treated patients the overall outcome of prophylaxis was clearly successful. Mild and transient oropharyngeal candidosis was observed in two and three patients in the fluconazole and nystatin groups respectively. One patient randomized to fluconazole and two patients randomized to nystatin required empirical treatment with amphotericin B and one patient assigned to fluconazole developed tissue-proven candida colitis. Initially non-colonized patients remained yeast-free throughout treatment with no differences between the two study arms. Initially colonized patients stayed colonized throughout treatment although at the end of the study, more patients randomized to nystatin were still harbouring yeasts (P = 0.05). Almost exclusively, Candida albicans (95%) was isolated. A change in species was observed in one patient in each arm of the study. Candida krusei or Candida glabrata were not encountered. Transient elevations of hepatic transaminases were more common in the fluconazole group, although not statistically significant (28% vs 12%, P = 0.15). Reversible grade I gastrointestinal and skin symptoms were observed in four patients randomized to fluconazole (16 vs 0%, P < 0.05). Fluconazole was as safe and effective as nystatin in controlling yeast colonization and in preventing superficial and invasive candida infections and the empirical use of amphotericin B in children and adolescents undergoing intensive chemotherapy for cancer. The aim of this study was to determine if radiotherapy induces hyposalivation altering oral microbial flora. The purpose of this placebo-controlled, single-blind study was to determine beneficial effects of a saliva substitute and an oral hygiene product on irradiated patients with oropharyngeal cancer. Eighteen patients were assigned to the test group (Biotène Oral Balance gel [Lacléde Incorporated Healthcare Products, Gardena, CA] and toothpaste used daily), and another 18 were put on a conventional daily regimen (carboxymethylcellulose gel and Oral-B toothpaste [Laclede Pharmaceuticals, Gardena, CA]). Cultures for identifying and quantitating microorganisms, whole unstimulated saliva, and visual analog measurements for comfort were obtained before mucositis occurred and after treatment. Daily use of Biotène products enhanced control of microbial flora, improved salivary flow, and increased oral comfort as compared with control subjects. Four weeks after mucositis, some aerobic isolates disappeared in the test group; periodontal-associated bacteria were markedly decreased in the test group; and candidal species were significantly lowered in the test group. Although baseline saliva was lower in the test group (P = 0.001), after 4 weeks, no difference between groups existed; comfort was greater in the test group (P = 0.007). Use of enzyme-engineered Biotène products that assist in control of the oral microbial flora as well as supporting oral comfort through lubrication appear to be useful aids for irradiated patients with oropharyngeal cancer. Fluconazole 50 mg daily for 14-28 days was effective in the treatment of patients with AIDS and AIDS-related complex with severe oropharyngeal and oesophageal candidiasis. Of 24 patients entered, 17 (81%), including seven with oesophageal candidiasis, were clinically cured and two (9.5%) improved at the end of treatment. Following clinical cure, 14 patients were entered into the double-blind phase of the study, where fluconazole (150 mg) or placebo capsules were given once weekly. Treatment was double blind. Fluconazole 150 mg once weekly was found to be effective in maintaining patients both clinically and mycologically free of oropharyngeal candidiasis.
There is strong evidence, from randomised controlled trials, that drugs absorbed or partially absorbed from the GI tract prevent oral candidiasis in patients receiving treatment for cancer. There is also evidence that these drugs are significantly better at preventing oral candidiasis than drugs not absorbed from the GI tract.