Lactoferrin supplementation for taste and smell abnormalities among patients receiving cancer chemotherapy.

PURPOSE: Taste and smell abnormalities (TSA) are common in patients receiving chemotherapy and may lead to altered nutritional intake, treatment withdrawal, and impaired quality of life. Lipid peroxidation in the oral cavity is one cause of TSA. Lactoferrin (LFN), an iron-binding salivary protein, reduces production of lipid oxidation byproducts and has been shown to reduce perception of unpleasant flavors. To assess the feasibility of LFN as a treatment for TSA, we conducted pilot investigations among patients with cancer who self-reported TSA following onset of chemotherapy. The primary objective was to assess change in subjective taste and smell perception from baseline to completion of 30 days of LFN supplementation. METHODS: Patients were treated with 750 mg LFN daily for 30 days and followed for an additional 30 days without LFN. TSA was measured via the taste and smell questionnaire (TSQ) including taste (score 0-10), smell (score 0-6), and composite scores (0-16) (0 = no TSA) at baseline, day 30, and day 60. RESULTS: A total of 26 patients enrolled; 19 remained on study at day 30 and 17 at day 60. Baseline mean TSQ scores were 6.5 (taste), 3.1 (smell), and 9.6 (composite). By day 30, mean composite TSQ score improved by 1.7 (p = 0.018); taste and smell improved by 0.6 (p = 0.062) and 1.1 (p = 0.042), respectively. From baseline to day 60, mean composite TSQ score improved by 3.8 (p < 0.0001); taste and smell improved by 1.9 (p = 0.001) and 1.8 (p = 0.003). CONCLUSIONS: Further evaluation of LFN is warranted to determine its value for improving self-reported TSA among patients receiving chemotherapy.

Effect of lactoferrin on taste and smell abnormalities induced by chemotherapy: a proteome analysis.

Cancer patients receiving chemotherapy often experience taste and smell abnormalities (TSA). To date, the underlying molecular mechanisms of this frequent side-effect have not been determined and effective treatments are not available. This study assessed the feasibility of lactoferrin (LF) supplementation as a treatment for TSA and investigate the related mechanisms through salivary proteome analysis. Nineteen cancer patients with established TSA following chemotherapy administration were enrolled in this study. Cancer patients and additional 12 healthy subjects took LF supplements, 3 tablets per day (250 mg per tablet), for 30 days. Saliva was collected at three timepoints: baseline, 30-day LF supplementation, and 30-day post-LF supplementation. Patient's TSA level, salivary proteome, and salivary minerals at each LF treatment stage were analyzed. High TSA level was associated with high concentration of salivary Fe and loss of critical salivary immune proteins. LF supplementation significantly decreased the concentration of salivary Fe (P = 0.025), increased the abundance (P < 0.05) of salivary α-amylase and Zn-α-2-GP, and led to an overall increase of expression (≥2-fold changes) of immune proteins including immunoglobulin heavy chain, annexin A1, and proteinase inhibitor. Abundance of α-amylase and SPLUNC2 were further increased (P < 0.05) at 30-day post-LF supplementation in cancer patients. At the same time, total TSA score was significantly reduced (P < 0.001) in chemotherapy patients. This study demonstrated the feasibility of developing lactoferrin supplementation as a treatment to reduce TSA caused by chemotherapy and improve cancer patient's oral immunity.

Exploring an Integrative Patient-Tailored Complementary Medicine Approach for Chemotherapy-Induced Taste Disorders.

CONTEXT: Chemotherapy-induced taste disorder (CITD) is a common adverse effect among patients with cancer, with no effective known treatment. OBJECTIVES: Exploring the impact of a patient-tailored complementary and integrative medicine (CIM) treatment program on CITD-related severity. DESIGN: Prospective study on patients' chart. SETTING: Integrative oncology program operating within the Clalit Healthcare Oncology Service in northern Israel. PATIENTS: Patients were referred by their oncology healthcare practitioner to a consultation with a CIM-trained integrative physician (IP). A patient-tailored CIM treatment program was designed, addressing quality of life (QOL)-related concerns which were evaluated using the Edmonton symptom assessment scale (ESAS) and the measure yourself concerns and well-being (MYCAW) questionnaires. RESULTS: A total of 626 patients were referred to the IP consultation, with CITD-related symptoms identified in 43, 34 of them returning for follow-up. The majority of patients treated with CIM reported a reduction in symptom severity (n = 29), with only three reporting no change, 2 an "unclear effect" and none a worsening of CITD-related symptoms. Acupuncture and herbal medicine (sage, carob, and wheatgrass juice, as mouthwash or applied to the oral mucosa) were the most frequently CIM modalities used. Assessment was considered optimal for 18 of the 29 patients who reported an improvement in ESAS scores for fatigue, drowsiness and depression. We conclude that a patient-tailored CIM program is a potentially effective and safe therapeutic option for CITD-related symptoms. Further research is needed in order to explore the impact of CIM treatments on taste and appetite-related concerns during chemotherapy.

From the Cover: Drug-Induced Taste Disorders in Clinical Practice and Preclinical Safety Evaluation.

More than 200 medications can induce taste disorders in patients. They not only reduce quality of life for those affected, but can lead to malnutrition, severe dehydration and difficulty in maintaining a therapeutic regimen. Nevertheless, the impact of drug candidates on taste is rarely evaluated in preclinical toxicology studies during the early stage of drug development. Moreover, knowledge about how to investigate these adverse effects is scarce in the toxicology field. Here, we discuss the clinical status of drug-induced taste disorders in patients, with the goal of providing toxicologists with a broad understanding of its prevalence, and how stressful and even dangerous it can be to affected patients. Because taste, smell, and oral trigeminal sensation are highly interdependent, we also address drug-induced changes in olfactory and oral somatosensory perceptions. We then review the biology of the gustatory system (including anatomy and histology), and the latest developments about how taste contributes to flavor perception. Finally, we feature recently optimized preclinical approaches to investigate drug-induced taste change in animal models, including morphological evaluation of taste buds and taste cells, gustatory nerve recording, and behavioral testing. Our goals are to raise awareness of drug-induced taste disorders among toxicologists, share an overview of new approaches and key studies that can be used to identify drug-induced gustatory system toxicity early in the drug development process, and to stimulate further research at this emerging interface of chemosensory disorders with toxicology.

Metallic taste in cancer patients treated with chemotherapy.

BACKGROUND: Metallic taste is a taste alteration frequently reported by cancer patients treated with chemotherapy. Attention to this side effect of chemotherapy is limited. This review addresses the definition, assessment methods, prevalence, duration, etiology, and management strategies of metallic taste in chemotherapy treated cancer patients. METHODS: Literature search for metallic taste and chemotherapy was performed in PubMed up to September 2014, resulting in 184 articles of which 13 articles fulfilled the inclusion criteria: English publications addressing metallic taste in cancer patients treated with FDA-approved chemotherapy. An additional search in Google Scholar, in related articles of both search engines, and subsequent in the reference lists, resulted in 13 additional articles included in this review. Cancer patient forums were visited to explore management strategies. FINDINGS: Prevalence of metallic taste ranged from 9.7% to 78% among patients with various cancers, chemotherapy treatments, and treatment phases. No studies have been performed to investigate the influence of metallic taste on dietary intake, body weight, and quality of life. Several management strategies can be recommended for cancer patients: using plastic utensils, eating cold or frozen foods, adding strong herbs, spices, sweetener or acid to foods, eating sweet and sour foods, using 'miracle fruit' supplements, and rinsing with chelating agents. INTERPRETATION: Although metallic taste is a frequent side effect of chemotherapy and a much discussed topic on cancer patient forums, literature regarding metallic taste among chemotherapy treated cancer patients is scarce. More awareness for this side effect can improve the support for these patients.

Efficacy of the Mentha crispa in the treatment of women with Trichomonas vaginalis infection.

PURPOSE: The aim of this study was to evaluate the efficacy of Mentha crispa in the treatment of women with Trichomonas vaginalis infection (TVI). METHODS: This was a randomized, double-blind, and controlled clinical trial consisting of three phases, pre-treatment, treatment, and post-treatment. Sixty female patients were randomized to a treatment group, M. crispa (24 mg) or secnidazole (2,000 mg), both consisting of single dose. RESULTS: After treatment the proportion of patients without TVI in secnidazole group was 96.6% and in the M. crispa group was 90%, no difference was found between groups (P = 0.6120). We observed improvement in vaginal discharge, malodorous vaginal secretion, dyspareunia, dysuria, pelvic pain, and burning and itching in the genital area in patients of both groups of treatment, with no statistically significant differences between them (P > 0.05). Adverse effects were significantly higher (P = 0.0006) in the secnidazole group (66.6%) than in the M. crispa group (20%), that being mostly nausea and metallic taste with statistically significant differences between treatment groups (P < 0.001). CONCLUSION: This study is the first to show that M. crispa is effective and safe, representing an alternative for the treatment of TVI in women.

Comparison of therapeutic effect of aqueous extract of garlic and nystatin mouthwash in denture stomatitis.

INTRODUCTION: Denture stomatitis (DS) is the most common form of chronic oral candidiasis. The standard treatment for DS is nystatin, which is accompanied with complications such as a bitter taste. The aim of this study was to compare the effect of garlic with nystatin in DS. MATERIAL AND METHODS: This randomised clinical trial study was performed on 40 patients with DS. After obtaining written consent, patients were divided into two groups while members of each group were given either nystatin or garlic extract for 4 weeks. The length and width of erythema area was measured at the end of the first, second, third, and the fourth weeks using a calliper. Data were analysed by SPSS and statistical tests including variance analysis with anova repeated measures, chi-square, and least square differences. RESULTS: The changes in the length and width of erythema at different times according to the type of treatment were found to be significant while an accelerated recovery was demonstrated for nystatin (p < 0.001). Both regimens resulted in significant recovery (p < 0.0001). Greater satisfaction with the use of garlic rather than nystatin was mentioned (p < 0.0001). CONCLUSION: Considering the efficacy of garlic and lack of side effects for this compound and also regarding the nystatin-associated complications, garlic extract can be introduced as a substitution for standard treatment in DS.

Loss of taste responds to high-dose biotin treatment.

BACKGROUND AND OBJECTIVE: We saw 2 patients who lost their sense of taste, which was restored by pharmacologic doses of biotin. The key objective is to describe the 2 case reports and suggest a potential treatment for unexplained loss of taste. METHODS AND DESIGN: The first patient was a 67-year-old woman who lost her sense of taste taking Juvenon, a dietary herbal supplement containing acyl-L-carnitine, lipoic acid, calcium, phosphorus, and biotin 300 µg per day. The second patient was a 60-year-old man who lost his sense of taste after a sleeve gastrectomy for obesity. RESULTS: The first patient did not respond to 5 mg per day of biotin, but taste was restored with 10 mg of biotin per day. Biotin was prescribed based on information that lipoic acid bound to the biotin transporter. Baseline urine gave no evidence of a pre-existing biotin deficiency. The second patient did not have restoration of taste after taking biotin 5 mg per day for 7 weeks but did have taste restoration on biotin 20 mg per day. Neither subject had an abnormal biotinidase level. CONCLUSIONS: Further research into the relationship of biotin to taste is clearly indicated. Loss of taste was very distressing and significantly altered the quality of life for both patients. Since biotin up to 40 mg per day has been shown to be safe, a therapeutic trial of pharmacologic doses of biotin should be considered as a potentially curative treatment in patients who present with a loss of taste that has no obvious cause.

Short-term clinical effects of commercially available gel containing Acacia arabica: a randomized controlled clinical trial.

BACKGROUND: Certain plants used in folk medicine serve as a source of therapeutic agent by having antimicrobial and other multi-potential effects. This prospective, randomized, placebo and positively controlled clinical trial was designed to evaluate the short-term clinical effects of a commercially available gel containing Acacia arabica in the reduction of plaque and gingival inflammation in subjects with gingivitis. METHODS: Ninety subjects diagnosed with chronic generalized gingivitis were selected and randomly divided into three groups: Group I - placebo gel, Group II - gumtone gel and Group III - 1% chlorhexidine gel. Clinical evaluation was undertaken using the gingival index of Loe and Silness and the plaque index at baseline, 2 weeks, 4 weeks and 6 weeks. A subjective evaluation was undertaken by questionnaire. RESULTS: Gumtone gel showed significant clinical improvement in gingival and plaque index scores as compared to a placebo gel. This improvement was comparable to 1% chlorhexidine gel. Unlike chlorhexidine gel, gumtone gel was not associated with any discolouration of teeth or unpleasant taste. CONCLUSIONS: Gumtone gel may be a useful herbal formulation for chemical plaque control agent and improvement in plaque and gingival status.

[Incidence of taste disorder associated with cancer patients undergoing chemotherapy on an ambulatory basis].

Taste disorders are a common complaint among cancer patients undergoing chemotherapy on an ambulatory basis. We conducted a survey on the incidence of such disorders among 74 patients, and 45.95% (34 of 74 patients) developed taste disorders. When stratified by medication into a regimen including 5-FU and one including taxanes, taste disorders were found in 59.0% (23 of 39 patients) of the former and 60.0% (9 of 15) of the latter. The survey also included the effects of taste disorders on patients appetites. Both regimens led to reduced appetite in a number of these patients (39.1% and 44.4%, respectively). Among patients on the 5-FU-containing regimen, the FOLFOX/FOLFIRI therapy was found to be responsible for loss of appetite. Regarding change in tastes, many patients stated that the medication dulled their taste sensation except for bitterness; their capacity to sense intensity of taste remained unchanged. It was found that acute taste disorders develop frequently among patients on a high dosage of 5-FU or a taxane-containing regimen.

The effects of an essential oil and an amine fluoride/stannous fluoride mouthrinse on supragingival plaque regrowth.

BACKGROUND: The side effects of chlorhexidine (CHX) have stimulated the search for alternative antiplaque agents such as amine fluoride/stannous fluoride (ASF) and essential oils (EO). The aim of the study was to investigate the plaque-inhibiting effects of two commercially available mouthrinses containing ASF and EO, respectively. METHODS: The study was an observer-masked, randomized, 5 x 5 Latin square cross-over design, balanced for carryover effects, involving 15 volunteers in a 4-day plaque regrowth model. A 0.12% CHX rinse and a saline solution served as positive and negative controls, respectively. On day 1, subjects received professional prophylaxis, suspended oral hygiene measures, and commenced rinsing with their allocated rinses. On day 5, subjects were scored for disclosed plaque. The ASF rinse was tested at two dosages: 10 and 20 ml (ASF-10 and ASF-20, respectively). RESULTS: The ASF and EO rinses showed a significant inhibition of plaque regrowth compared to saline (P <0.0001), but the lowest plaque indices were obtained with the CHX product (P <0.01). There were no significant differences among products containing ASF-10, ASF-20, and EO (P >0.05). There was no correlation between the occurrence of side effects and the use of a particular rinse product (P >0.2). CONCLUSIONS: ASF and EO mouthrinses exerted effective and similar plaque inhibition. The two dosages tested for ASF did not differ in plaque reduction. These findings, together with those from long-term trials, suggest that ASF and EO rinses may represent effective alternatives to CHX rinse as adjuncts to oral hygiene.

Oral mucosal lesions, microbial changes, and taste disturbances induced by adjuvant chemotherapy in breast cancer patients.

OBJECTIVE: The aim of the study was to examine oral mucosal lesions, microbial changes, and taste disturbances induced by adjuvant chemotherapy (CT) in breast cancer patients during and 1 year after treatment. STUDY DESIGN: Forty-five consecutive breast cancer patients, eligible for adjuvant CT with cyclophosphamide, epirubicin or methotrexate, and 5-fluorouracil were followed before, during, 6 months and 1 year after CT and were compared to a control group of 31 breast cancer patients not receiving adjuvant CT. RESULTS: During CT, oral mucosal lesions developed including erythema (n = 10, 22%) and ulceration (n = 7, 16%). Five patients (11%) were diagnosed with oral candidosis. Scores of dental bacterial plaque and gingival inflammation increased during CT and the oral microbial composition changed towards a more acidophilic flora. Taste disturbances were experienced by 84% (n = 38) of the patients in the CT group. CONCLUSION: In breast cancer patients, moderate-intensive adjuvant CT caused oral mucosal lesions, oral candidosis, taste disturbances and a more acidophilic oral microflora. These adverse effects were temporary and the majority of the patients were mildly affected.

Terbinafine hydrochloride oral granules versus oral griseofulvin suspension in children with tinea capitis: results of two randomized, investigator-blinded, multicenter, international, controlled trials.

BACKGROUND: Although griseofulvin is currently considered the primary antifungal agent used to treat tinea capitis in many countries, increasingly higher doses and longer durations of treatment are becoming necessary to achieve effective treatment. Alternative antifungal therapies with shorter/simpler treatment regimens may be important to develop for this indication. OBJECTIVE: To compare the efficacy and safety of a new pediatric formulation of terbinafine hydrochloride oral granules with griseofulvin oral suspension in the treatment of tinea capitis. METHOD: Children (4-12 years of age) with clinically diagnosed and potassium hydroxide microscopy-confirmed tinea capitis were randomized in two identical studies (trial 1, trial 2) to once-daily treatment with terbinafine (5-8 mg/kg; n = 1040) or griseofulvin administered per label (10-20 mg/kg; n = 509) for a period of 6 weeks followed by 4 weeks of follow-up. End-of-study complete cure (negative fungal culture and microscopy with Total Signs and Symptoms Score [TSSS] = 0), and mycologic (negative culture and microscopy) and clinical cure (TSSS = 0) were primary and secondary efficacy variables, respectively. Efficacy analysis was based on pooled data using modified intent-to-treat population (those who received at least one dose of study drug and had positive baseline fungal culture, N = 1286). Safety assessments included monitoring of the frequency and severity of adverse events (AEs). RESULTS: Rates of complete cure and mycologic cure were significantly higher for terbinafine than for griseofulvin (45.1% vs 39.2% and 61.5% vs 55.5%, respectively; P < .05). A majority (86.7%) of patients received griseofulvin, 10 to 19.9 mg/kg per day; complete cure rate was not found to be higher among patients who received griseofulvin more than 20 mg/kg per day compared with those who received less than 20 mg/kg per day. Complete cure rate was statistically significantly greater for terbinafine compared to griseofulvin in trial 1 (46.23% vs 34.01%) but not in trial 2 (43.99% vs 43.46%). On the basis of pooled data, clinical cure was higher for terbinafine than for griseofulvin, but the difference was not found to be statistically significant (P = .10). Subgroup analyses revealed that terbinafine was significantly better than griseofulvin for all cure rates--mycologic, clinical, and complete--among patients with Trichophyton tonsurans but not Microsporum canis (P < .001). For M. canis, mycologic and clinical cure rates were significantly better with griseofulvin than with terbinafine (P < .05). Approximately 50% of patients in each group reported an AE; almost all were mild or moderate in severity. Nasopharyngitis, headache, and pyrexia were most common in both groups. There were no drug-related serious AEs, no deaths, and no significant effects on weight or laboratory parameters, including liver transaminases. LIMITATIONS: In retrospect, a difference in the distribution of infecting microorganisms between the two trials was a limitation. Stringent adherence to griseofulvin doses recommended by prescribing information but smaller than those used in current clinical practice, and exclusion of adjuvant therapies such as shampoos or topical agents, which are routinely used in practice, are other limitations. CONCLUSIONS: Data from this largest pediatric trial of terbinafine to date indicate that terbinafine is efficacious and well tolerated in the treatment of tinea capitis. Terbinafine is an effective alternative to griseofulvin against T. tonsurans tinea capitis.

Combination of flavor enhancement and chemosensory education improves nutritional status in older cancer patients.

BACKGROUND: Abnormalities in taste and smell functioning occur with elevated frequency in both older adults and patients with cancer. With the predicted increase in both of these populations in the coming decades, it is imperative to evaluate potential interventions that are designed to help older cancer patients compensate for the additive burden of this disease and its treatment on age-related taste and smell losses. OBJECTIVE: The purpose of the current study was to determine if providing instruction and products for flavor enhancement of foods to elderly cancer patients in addition to nutritional information would improve their nutritional status, and, by extension, functional and immune status as well as quality of life. DESIGN: One hundred and seven subjects enrolled in the study. Fifty-four subjects were in the experimental group that received flavor enhancement plus nutritional information; fifty-three control subjects received only nutritional information. Subjects were evaluated 1 month, 3 months, and 8 months after beginning chemotherapy. At every session, subjects completed taste and smell assessments as well as questionnaires related to nutritional status, activities of daily living, and quality of life. Blood samples were also obtained to determine immune parameters. RESULTS: At the eight-month time point, experimental subjects had better scores on the mini nutritional assessment (MNA) and the physical function assessment of the quality of life questionnaire. Also at eight months, self-reported taste and smell perception for experimental subjects was better than that of controls as well as better than at earlier time points. Tests that assessed quantity and quality of food intake, as well as a number of immune parameters declined over time and did not differ significantly between groups. CONCLUSION: The combination of flavor enhancement, chemosensory education, and nutritional information for elderly cancer patients improved their nutritional assessment on the MNA and physical function over time. On the whole, experimental subjects perceived themselves to be better functioning at eight months than did their control counterparts.

[Adverse drug effects in the oral region]. / Legemiddelbivirkninger i munnhulen.

Syphilis was previously termed "the great imitator" because so many of the signs and symptoms are indistinguishable from those of other diseases. This role has been taken over by drugs, and this also applies to adverse drug reactions in the oral region. Accordingly, a careful drug history, including identification of any prescription, over-the-counter, or herbal medicines used, may give an important clue to the differential diagnosis of oral diseases when the aetiology is not apparent. Virtually all drugs have the potential to cause oral adverse reactions, but some have a greater ability to do so than others. Among the numerous adverse oral manifestations are xerostomia, taste disturbances and ulceration. The reactions are often non-specific, but they may mimic specific disease states such as erythema multiforme, lichen planus and pemphigus. Drug-induced gingival hyperplasia is an example of a quite characteristic and easily recognisable oral side effect. This article briefly describes some of the presentations and mechanisms of oral manifestations of drug therapy and the drugs that most commonly are responsible. Just like approved pharmaceuticals, herbal medicines are also associated with adverse oral manifestations. Finally we comment on some of the more recent reports on osteonecrosis of the jaws associated with the use of bisphosphonates.

[Metal intolerance. A frequent condition, but difficult to diagnose]. / Metall-Unverträglichkeit. Eine häufige Erkrankung, aber schwierig zu diagnostizieren.

Many of the methods and devices used for incompatibility testing of metals and alloys today are of questionable scientific value. Neither epicutaneous testing nor other diagnostic adjuncts from the realm of alternative medicine, nor patient-history data contained in so-called dental alloy passports, are generally able to yield any useful information. Analysis is particularly difficulty in situations where metallic components are cemented in place in the oral cavity. For many years now, the so-called splinter test has proven its value as a means of non-destructively identifying the type of alloy used. It can also be used for detecting persistent corrosion-prone adhesive oxides and soldering joints as causative agents of metal-related noxious processes. This article presents a number of case reports to demonstrate the reliability and the precision of the splinter test. Over a period of 10 years, more than 1600 splinter analyses have been performed at the University of Basle Center of Dentistry. According to a pertinent survey, these analyses were able to contribute to full treatment success in 63% of the cases, to partial success in 27% of the cases, and to no success in only 10% of the cases.

Oral manifestations of drug therapy.

The oral cavity may be the target organ for a number of diverse abnormalities that develop from side effects of medications. Because of the widespread and increasing use of prescription, over-the-counter, and herbal remedies, it is becoming increasingly likely that the dentist will encounter soft tissue or dental pathologies that represent a complication of a therapeutic agent. The more common abnormalities that may occur include gingival hyperplasia, tooth discoloration, candidiasis, chemical injuries, and altered taste perception. The dental practitioner is often the primary health care provider who can recognize, diagnose, treat, and/or prevent these conditions.

A long-term, multicenter study of the efficacy and safety of paricalcitol in end-stage renal disease.

BACKGROUND: Paricalcitol is a vitamin D analog approved for the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure. This study was designed to evaluate the long-term efficacy and safety of paricalcitol. Additional analysis evaluated the effects of paricalcitol in hypocalcemic and hyperphosphatemic subpopulations. PATIENTS AND METHODS: One hundred sixty-four end-stage renal disease (ESRD) patiesnts on hemodialysis were treated in an open-label, multicenter study lasting up to 13 months in duration. After a baseline or washout period, an initial starting dose of 0.04-0.393 microg/kg was given 2-3 times per week. This dose was adjusted at the discretion of the investigator according to the patient's intact parathyroid hormone level (iPTH), calcium level, and calcium-phosphorus (Ca x P) product. The therapy was intended to reproduce expected clinical use of paricalcitol. Patients represented a wide cross-section of the ESRD population, and were not excluded from the study based on age or underlying disease. RESULTS: The mean paricalcitol dose level throughout the study was 0.10 microg/kg. The mean iPTH levels (baseline mean 628.3 +/- 27.65 pg/ml) decreased rapidly during the first 4 months of therapy, and reached the designated target range (100-300 pg/ml) by month 5 (mean 295.3 +/- 25.69 pg/ml). A maximum mean decrease in iPTH level of 409 +/- 35.01 pg/ml was seen at month 13. Throughout the course of the study, the mean normalized calcium level was maintained well within the normal range (9.44-9.94 mg/dl). The mean phosphorus level was maintained in an acceptable range throughout the study (5.92-6.53 mg/dl). Mean Ca x P product was maintained between 52 and 65. Mean alkaline phosphatase levels decreased significantly from baseline with a maximum mean decrease of 62 +/- 17.3 U/l observed at month 9. In 34 initially hypocalcemic patients (mean of 7.7 mg/dl) iPTH levels decreased from baseline, on average, by 443 +/- 81.86 pg/ml while mean calcium levels rose by 1.2 +/- 0.23 mg/dl to reach the normal range. In 35 initially hyperphosphatemic patients (mean of 8.0 mg/dl) iPTH levels decreased, on average, by 515 +/- 103.31 pg/ml with an associated mean decrease in phosphorus of 0.57 +/- 0.52 mg/dl. Adverse events that were considered by the investigator to have a possible. probable, or definite relationship to study drug occurred in 26% of patients. Other than expected temporary effects of hypercalcemia and hyperphosphatemia. the only possible trends for causally-related adverse events were for nausea/vomiting and metallic taste. CONCLUSIONS: This long-term study of paricalcitol demonstrates that it rapidly and effectively suppresses iPTH levels in a wide spectrum of ESRD patients and caused no unexpected adverse events.