Evaluation of Chemotherapy-induced Dysgeusia in Patients With Gastrointestinal Cancer: A Pilot Study.

BACKGROUND/AIM: Dysgeusia, one of the adverse effects of cancer chemotherapy, and anorexia due to taste disorder can significantly impair the quality of life of patients. However, an evaluation method for dysgeusia has not yet been established. The present prospective study aimed to utilize a combination of subjective and objective assessment methods to evaluate dysgeusia in patients with gastrointestinal cancer initiating chemotherapy, to determine chemotherapeutic drugs and regimens causing dysgeusia, and to assess whether dysgeusia was associated with zinc deficiency. PATIENTS AND METHODS: A total of 21 patients with newly diagnosed gastrointestinal cancer were registered between August 2020 to March 2021. The following regimens were also included in the evaluation if the patients did not develop dysgeusia. A total 30 regimens were administered to the patients during the study period. A salt-impregnated test paper (Salsave®) was used as a subjective assessment, and the chemotherapy-induced taste alteration scale was used as an objective assessment. RESULTS: Based on physician interviews, dysgeusia was diagnosed in 8 of 21 patients (38%) treated with 8 of 30 regimens (27%). All regimens that resulted in dysgeusia contained platinum-based drugs. The patients who developed dysgeusia had higher controlling nutritional status scores at the start of chemotherapy compared to those who did not develop dysgeusia. In both subjective and objective assessments, the patients with dysgeusia performed significantly worse than those without dysgeusia. Six of the eight patients who developed dysgeusia were administered Novelzine, which did not improve the taste disorder despite the improvement of serum zinc levels. CONCLUSION: The combined approach using subjective and objective taste assessment methods was useful in assessing chemotherapy-induced dysgeusia. Mechanisms other than hypozincemia should be considered as contributors to taste disorders caused by platinum-based drugs.

Therapeutic effects of clonazepam in patients with burning mouth syndrome and various symptoms or psychological conditions.

Burning mouth syndrome (BMS) is frequently accompanied by dysgeusia and xerostomia. Clonazepam has been widely prescribed and is effective, but it is unclear whether clonazepam also affects the symptoms that accompany BMS, or whether such symptoms affect treatment outcomes. Here, we investigated the therapeutic outcomes in BMS patients with various symptoms or comorbidities. We retrospectively reviewed 41 patients diagnosed with BMS between June 2010 and June 2021 at a single institution. Patients were instructed to take clonazepam for 6 weeks. Before the first dose, burning pain intensity was measured using a visual analog scale (VAS); the unstimulated salivary flow rate (USFR), psychologic characteristics, site(s) of pain, and any taste disturbance were evaluated. Burning pain intensity was measured again after 6 weeks. Thirty-one of the 41 patents (75.7%) exhibited a depressed mood, whereas more than 67.8% of the patients exhibited anxiety. Subjective xerostomia was reported by ten patients (24.3%). The mean salivary flow rate was 0.69 mL/min and hyposalivation (an unstimulated salivary flow rate ≤ 0.5 mL/min) was apparent in ten patients (24.3%). Dysgeusia was present in 20 patients (48.7%); a bitter taste (n = 15, 75%) was reported by the largest proportion of patients. Patients who reported a bitter taste responded best in terms of burning pain reduction after 6 weeks (n = 4, 26.6%). Overall, 32 patients (78%) reported decreased oral burning pain after clonazepam (mean VAS score changed from 6.56 to 5.34) use. Patients who reported taste disturbances exhibited a significantly greater decrease in burning pain, compared with other patients (mean VAS score changed from 6.41 to 4.58) (p = 0.02). Clonazepam significantly improved burning pain in BMS patients who had taste disturbances.

Acupuncture in chemotherapy-induced dysgeusia (AcuDysg): study protocol of a randomised controlled trial.

INTRODUCTION: Dysgeusia is a common side effect of chemotherapy in patients with cancer, but to date, there is no effective treatment. Many patients with cancer request complementary medicine treatment in addition to their cancer treatments, and acupuncture is highly accepted for patients with cancer; however, evidence regarding the effectiveness of acupuncture for dysgeusia is scarce.The study investigates the effectiveness of an additional dysgeusia-specific acupuncture plus self-acupressure intervention compared with supportive acupuncture plus self-acupressure intervention alone for chemotherapy-induced dysgeusia in patients with cancer. METHODS AND ANALYSIS: This is a multicentre, randomised, controlled and two-armed parallel-group, single-blind trial involving 130 patients. Both groups will receive eight sessions of acupuncture treatment over a period of 8 weeks and will be trained to perform self-acupressure (eLearning combined with therapist instruction) at predefined acupressure points once a day during the whole treatment period. Patients in the control group will receive supportive routine care acupuncture and self-acupressure treatment only; in addition to this treatment, the intervention group will receive the dysgeusia-specific acupuncture and acupressure within the same treatment session. The primary outcome is the perceived dysgeusia over 8 weeks, measured weekly after the acupuncture treatment. Secondary outcomes include the indices from the objective taste and smell test, weight loss, perceived dysgeusia, fatigue, distress, nausea and vomiting, odynophagia, xerostomia and polyneuropathy, as well as quality of life at the different time points. ETHICS AND DISSEMINATION: The study has been approved by the Cantonal Ethics Committee (CEC) (Kanton Zürich Kantonale Ethikkommission) (approval no. KEK-ZH-Nr. 2020-01900). The results will be submitted to a peer-reviewed journal for publication. TRIAL REGISTRATION NUMBERS: DRKS00023348, SNCTP000004128.

Efficacy and Safety of Sonic Hedgehog Inhibitors in Basal Cell Carcinomas: An Updated Systematic Review and Meta-analysis (2009-2022).

BACKGROUND: Basal cell carcinoma (BCC) of the skin is the most common form of skin cancer in the United States. In life-threatening, advanced BCC, sonic hedgehog inhibitors (SSHis) remain a pre-eminent treatment option for locally advanced BCC and metastatic BCC. OBJECTIVE: In this updated systematic review and meta-analysis, we aimed to better characterize the efficacy and safety of SSHis by including final updates from pivotal clinical trials and additional new recent studies. METHODS: An electronic database search was performed for articles including clinical trials, prospective case series, and retrospective medical record reviews on human subjects. Overall response rates (ORRs) and complete response rates (CRRs) were the primary outcomes. For safety assessment, the prevalence of the following adverse effects was analyzed: muscle spasms, dysgeusia, alopecia, weight loss, fatigue, nausea, myalgias, vomiting, skin squamous cell carcinoma, increased creatine kinase, diarrhea, decreased appetite, and amenorrhea. Analyses were performed using R statistical software. Data were pooled using linear models with fixed effects meta-analysis for primary analyses, along with 95% confidence intervals (CIs) and p-values. Intermolecular differences were calculated using Fisher's exact test. RESULTS: A total of 22 studies (N = 2384 patients) were included in the meta-analysis: 19 studies assessing both efficacy and safety, 2 studies assessing safety only, and 1 study assessing efficacy only. Overall, the pooled ORR for all patients was 64.9% (95% CI 48.2-81.6%), implicating there is at least a partial response (z = 7.60, p < 0.0001) in most patients receiving SSHis. The ORR for vismodegib was 68.5% and 50.1% for sonidegib. The most common adverse effects for vismodegib and sonidegib were muscle spasms (70.5% and 61.0%, respectively), dysgeusia (58.4% and 48.6%, respectively), and alopecia (59.9% and 51.1%, respectively). Patients were likely to experience weight loss (35.1%, p < 0.0001) from vismodegib. Alternatively, patients taking sonidegib experienced more nausea, diarrhea, increased creatine kinase levels, and decreased appetite compared with those receiving vismodegib. CONCLUSION: SSHis are an effective treatment for advanced BCC disease. Given the high discontinuation rates, management of patient expectations is warranted for compliance and achieving long-term efficacy. It is essential to stay updated with the latest discoveries on the efficacy and safety of SSHis.

Taste alterations during neo/adjuvant chemotherapy and subsequent follow-up in breast cancer patients: a prospective single-center clinical study.

PURPOSE: Dysgeusia and taste alterations (TAs) are side effects of cytotoxic chemotherapy and affect patients' quality of life; however, the prevalence, types, and duration of TAs and their potential relationship with other clinical disturbances are not well-described. Our primary aim was to prospectively evaluate the characteristics of TAs in early breast cancer (EBC) patients during (neo)adjuvant chemotherapy and up to 1 year after its completion. METHODS: From April 2014 to June 2018, 182 EBC patients entered the study and received (neo)adjuvant chemotherapy, mostly with taxane and anthracycline-containing regimens (65% of cases). A dietitian performed TAs assessment through the Common Terminology Criteria for Adverse Event v4.0 (CTCAE) and the Chemotherapy-induced Taste Alteration Scale (CiTAS) questionnaire during chemotherapy and follow-up according to defined time points: at baseline (T0, before starting chemotherapy); at the first follow-up visit, (T1, 2 months after starting chemotherapy); at the final follow-up visit (T2, 1 week after completing chemotherapy); after that, every 3 months up to 12 months. RESULTS: Dysgeusia was reported by 69.8% of patients at T1 and declined subsequently; salty flavor distortion was the most frequently reported TA (51.6% of cases). CiTAS was significantly different between T0 and T2 (p < 0.001). Dysgeusia occurred more frequently in patients reporting nausea, mucositis, diarrhea, and appetite modification. CONCLUSIONS: TAs are common but transient during chemotherapy and occurred frequently with other distressing gastrointestinal side effects. The assessment of these side effects is crucial in managing EBC patients during (neo)adjuvant chemotherapy.

Multicenter, prospective, observational study of chemotherapy-induced dysgeusia in gastrointestinal cancer.

PURPOSE: Dysgeusia is an adverse event caused by chemotherapy. Although retrospective studies have shown zinc administration improves dysgeusia, there have been no prospective studies. The present study examined effects of zinc therapy on dysgeusia in patients with gastrointestinal cancer. METHODS: This multicenter, prospective, observational study enrolled patients with dysgeusia during chemotherapy treatment. Patients received no intervention (control), polaprezinc p.o., or zinc acetate hydrate p.o., and serum zinc levels were measured at 0 (baseline), 6, and 12 weeks. Dysgeusia was assessed using CTCAE v5.0 and subjective total taste acuity (STTA) criteria using questionnaires at baseline and 12 weeks. RESULTS: From February 2020 to June 2021, 180 patients were enrolled from 17 institutes. There were no differences in mean baseline serum zinc levels among the groups (67.3, 66.6, and 67.5 µg/dL in the no intervention, polaprezinc, and zinc acetate hydrate groups, respectively. P = 0.846). The changes in mean serum zinc levels after 12 weeks were - 3.8, + 14.3, and + 46.6 µg/dL, and the efficacy rates of dysgeusia were 33.3%, 36.8%, and 34.6% using CTCAE and 33.3%, 52.6%, 32.7% using STTA in the no intervention, polaprezinc, and zinc acetate hydrate groups, respectively. The STTA scores improved in all groups, with significant improvement observed in the polaprezinc group compared with the no intervention group (P = 0.045). CONCLUSION: There was no significant correlation between the degree of serum zinc elevation and improvement in dysgeusia, suggesting that polaprezinc, but not zinc acetate hydrate, was effective in improving chemotherapy-induced dysgeusia. TRIAL REGISTRATION: UMIN000039653. Date of registration: March 2, 2020.

Zinc as a complementary treatment for cancer patients: a systematic review.

Zinc is a trace element that plays an important role in the immune system and cell growth. The role of zinc in cancer treatment has been discussed for some time, however without reaching an evidenced-based consensus. Therefore, we aim to critically examine and review existing evidence on the role of zinc during cancer treatment. In January 2019, a systematic search was conducted searching five electronic databases (Embase, Cochrane, PsychINFO, CINAHL and PubMed) to find studies concerning the use, effectiveness and potential harm of zinc therapy on cancer patients. Out of initial 5244 search results, 19 publications concerning 23 studies with 1230 patients were included in this systematic review. The patients treated with zinc were mainly diagnosed with head and neck cancer and underwent chemo-, radio- or concurrent radio-chemotherapy. Interventions included the intake of different amounts of zinc supplements and oral zinc rinses. Outcomes (primary endpoints) investigated were mucositis, xerostomia, dysgeusia, pain, weight, dermatitis and oral intake of nutrients. Secondary endpoints were survival data, quality of life assessments and aspects of fatigue, immune responses and toxicities of zinc. The studies were of moderate quality reporting heterogeneous results. Studies have shown a positive impact on the mucositis after radiotherapy. No protection was seen against mucositis after chemotherapy. There was a trend to reduced loss of taste, less dry mouth and oral pain after zinc substitution. No impact was seen on weight, QoL measurements, fatigue, and survival. The risk of side effects from zinc appears to be relatively small. Zinc could be useful in the prevention of oral toxicities during irradiation. It does not help in chemotherapy-induced side effects.

The effects of zinc on radiation-induced dysgeusia: a systematic review and meta-analysis.

PURPOSE: Many head and neck cancer patients who receive radiation therapy experience radiation-induced dysgeusia (RID), which has no standard treatment. The only supplement controlled clinical trials have evaluated for the treatment of RID is zinc. However, the results of these and other studies investigating the use of zinc for RID have been inconsistent. To assess the validity of zinc as a treatment for RID, we conducted a systematic literature search and performed a meta-analysis to determine the extent to which zinc affects RID incidence and the degree to which ongoing RID responds to zinc. METHODS: We searched the Ovid MEDLINE, Ovid Embase, PubMed, and Cochrane Library databases to identify studies investigating the use of zinc-based therapy for RID in head and neck cancer patients treated with radiation that were published between January 1, 2003, and November 9, 2017. Using American Society of Clinical Oncology criteria, we selected studies with a high level of evidence for inclusion in the meta-analysis. RESULTS: Of the 32 full-text articles eligible for inclusion, three were included in the final review and meta-analysis. The meta-analysis showed that, compared with placebo, zinc reduces the incidence of RID (risk ratio, 0.72; 95% confidence interval, 0.67-0.92) but does not improve taste acuity more rapidly following radiation therapy (risk ratio, 2.58; 95% confidence interval, 0.97-6.88). CONCLUSION: Our findings indicate that zinc-based therapy reduces the incidence of RID but has a minimal effect on ongoing RID. Our findings also highlight the need for additional evidence-based research on this topic.

Successful Management of Glioblastoma Chemotherapy-Associated Dysgeusia with Gabapentin.

Dysgeusia is a frequent, yet underreported side effect of chemotherapy for cancer. We report here the first use of gabapentin in two glioblastoma patients who developed dysgeusia following intra-arterial administration of carboplatin or oral administration of lomustine, respectively. Treatment initiation was followed by resolution of taste alteration within weeks. Both patients reported significant improvement in their quality of life and regained weight, allowing further chemotherapy cycles. We hypothesized that in these two cases, chemotherapy impeded gustatory cells turnover and function, resulting in a gustatory "deafferentation-like" syndrome which was successfully addressed by the medication.

Increase in Carbohydrate Antigen 19-9 Levels without Tumor Progression after Polaprezinc Administration that Induced Deep Vein Thrombosis in a Colon Cancer Patient.

Carbohydrate antigen 19-9 (CA 19-9) is a well-known tumor marker of adenocarcinoma (reference range, 37 U/mL). It can also be used, together with computed tomography, to monitor responses and resistance to chemotherapy in cancer patients. False elevation of CA 19-9 levels is often seen in conditions such as biliary tract obstruction and cholangitis. However, whether medication might induce false elevation of CA 19-9 levels has not yet been reported. A 74-year-old man was treated with third-line CPT-11 (irinotecan) plus panitumumab for stage IV cancer of the ascending colon. The patient developed chemotherapy-induced dysgeusia and was treated with polaprezinc. After polaprezinc administration, his CA 19-9 levels gradually increased from 18.9 to 1,699.4 U/mL. He developed deep vein thrombosis (DVT), although it was not associated with progressive disease or metastasis. Upon discontinuation of polaprezinc, CA 19-9 levels gradually decreased. This case demonstrates that polaprezinc may not only induce false elevation of CA 19-9 levels but also cause development of DVT induced by increased CA 19-9 levels, both of which are very rare events.

Improvement of Dysgeusia by Polaprezinc, a Zinc-L-carnosine, in Outpatients Receiving Cancer Chemotherapy.

BACKGROUND/AIM: Dysgeusia is one of the adverse events frequently affecting patients undergoing cancer chemotherapy. Dysgeusia-induced anorexia could decrease patient's quality of life. The present study was designed to determine whether the zinc-containing compound polaprezinc improves chemotherapy-induced dysgeusia. PATIENTS AND METHODS: The incidence of grade 2 dysgeusia was assessed in 634 patients receiving cancer chemotherapy in outpatient settings during January 2013 and June 2017. Polaprezinc was administered to patients showing grade 2 dysgeusia and the effect was compared with that in patients subjected to follow-up observation. RESULTS: Grade 2 dysgeusia appeared in 80 patients (12.6%), in whom pancreatic cancer and treatment with fluoropyrimidines were significant risks for dysgeusia. Polaprezinc, when administered to patients with grade 2 dysgeusia, significantly shortened the duration of dysgeusia compared with that in the follow-up observation group. Subgroup analysis indicated that polaprezinc was less effective in patients with pancreatic cancer, those receiving gemcitabine, or those whose age was 65 year-old and over. CONCLUSION: Chemotherapy-induced dysgeusia occurred with high frequency in patients with pancreatic cancer or in those receiving fluoropyrimidines. Polaprezinc was highly effective in improving the symptom of dysgeusia, except for patients with pancreatic cancer, those receiving gemcitabine and the elderly.

Successful treatment of dysgeusia after middle-ear surgery with amitriptyline: Case report.

INTRODUCTION: The chorda tympani branches off of the facial nerve within the petrous portion of the temporal bone, and is responsible for controlling the taste in the anterior two-thirds of the tongue on each side. Due to its location, it is commonly injured during middle-ear surgery resulting in dysgeusia. METHOD: A case of a 59-year-old male had recurrent otitis media resulting in tympanic membrane perforation. Patient subsequently underwent lateral graft tympanoplasty. Shortly after surgery patient reported onset of dysgeusia consisting of metallic taste at the tip of the tongue and salty taste on the left side of the tongue. RESULTS: Treatment with Amitriptyline 50mg each night significantly improved the patient's symptoms of dysgeusia. CONCLUSIONS: Amitriptyline may be an effective treatment for dysgeusia occurring after middle-ear surgery.

Intranasal theophylline treatment of hyposmia and hypogeusia: a pilot study.

OBJECTIVE: To determine whether intranasal theophylline methylpropyl paraben can correct hyposmia and hypogeusia. DESIGN: We performed an open-label pilot study in patients with hyposmia and hypogeusia under the following 3 conditions: (1) before treatment, (2) after oral theophylline anhydrous treatment, and (3) after intranasal theophylline treatment. Under each condition, we performed subjective evaluations of taste and smell functions, quantitative measurements of taste (gustometry) and smell (olfactometry), and measurements of serum theophylline level and body weight. SETTING: The Taste and Smell Clinic in Washington, DC. PATIENTS: Ten patients with hyposmia and hypogeusia clinically related to the effects of viral illness, allergic rhinitis, traumatic brain injury, congenital hyposmia, and other chronic disease processes were selected. INTERVENTIONS: Oral theophylline anhydrous, 200 to 800 mg/d for 2 to 12 months, was administered to each patient. This treatment was discontinued for 3 weeks to 4 months when intranasal theophylline methylpropyl paraben, 20 µg/d in each naris, was administered for 4 weeks. MAIN OUTCOME MEASURES: At termination of each condition, taste and smell function was determined subjectively, by means of gustometry and olfactometry, with measurement of serum theophylline levels and body weight. RESULTS: Oral theophylline treatment improved taste and smell acuity in 6 patients after 2 to 12 months of treatment. Intranasal theophylline treatment improved taste and smell acuity in 8 patients after 4 weeks, with improvement greater than after oral administration. No adverse effects accompanied intranasal drug use. Body weight increased with each treatment but was greater after intranasal than after oral administration. CONCLUSIONS: Intranasal theophylline treatment is safer and more effective in improving hyposmia and hypogeusia than oral theophylline anhydrous treatment.

Recovery from long-lasting post-tonsillectomy dysgeusia.

Transient post-tonsillectomy taste dysgeusia (PTD) is a common complaint. Long-lasting PTD is less frequent but has significant consequences on patients' quality of life, with some cases leading to medicolegal issues. Treatment options and knowledge about mechanisms and factors favoring PTD are limited. PTD may result from direct surgical injury, tongue compression, inflammatory processes or side effects of local anesthetics. Some authors also claim that dietary zinc deficiency plays a role in the development of PTD. Although this latter cause had not yet received a lot of attention, we report a case of a female patient who reported a 4-year PTD and recovered within 2 months after oral intake of zinc sulfate. This clinical observation, together with recent findings on significant improvement of taste disorders after zinc treatments for other causes, opens again the question of what extent zinc deficiency plays a role in PTD.

Prevention of docetaxel- or paclitaxel-associated taste alterations in cancer patients with oral glutamine: a randomized, placebo-controlled, double-blind study.

Taste alteration (dysgeusia), an underrecognized toxicity associated with taxane-based chemotherapy (TaxCh), lacks standard treatment. We investigated prevention of dysgeusia with oral glutamine in patients undergoing first-time TaxCh. Adult patients were randomized to receive either 30 g/day glutamine or placebo (maltodextrin) from day 1 of TaxCh. Dysgeusia was measured daily with a visual analogue scale (VAS). On each chemotherapy cycle, objective (sour, sweet, salty, bitter) and subjective (four-category scale) taste and toxicity (National Cancer Institute Common Toxicity Criteria, v.3) were assessed. Stomatitis and zinc deficiency were treated. For primary outcomes, repeated dysgeusia scores were analyzed with a linear mixed model. Repeated data on each objective or subjective taste item were analyzed with a generalized estimating equation. Of 52 patients randomized, 41 completed treatment (median study duration, 74 days). At baseline, the glutamine (n = 21) and placebo (n = 20) groups were comparable for age (64 years), gender (32% men), tumor types, chemotherapy (docetaxel, 44%; paclitaxel, 56%), schedule (weekly, 78%; 3-weekly, 22%), treatment intention (15% adjuvant), dysgeusia (VAS, 11/100), and taste recognition (88%). Twenty-four patients had peripheral neuropathy grades 1-2; none had grade 3. Glutamine and placebo were not different for maximal dysgeusia and increase from baseline, with an insignificant linear time effect. Separate subgroup analyses for patients with baseline dysgeusia < or =11 or >11 did not alter the results. Objective or subjective taste tests were not different, neither were adverse events. Compared with placebo, oral glutamine did not prevent or decrease subjective taste disturbances or altered taste perception associated with TaxCh. The role of glutamine in supportive care of taxane-associated dysgeusia seems limited.

A case of Cronkhite-Canada syndrome with taste disturbance as a leading complaint.

Cronkhite-Canada syndrome was first described in 1955. The clinical features of this rare syndrome of unknown etiology include nonhereditary gastrointestinal polyposis together with diarrhea, nail dystrophy, alopecia, and hyperpigmentation of the skin. This syndrome has been divided into five clinical types based on initial symptoms. We describe a case of Cronkhite-Canada syndrome presenting with taste disturbance as the major symptom, present a comprehensive review of the literature concerning this rare syndrome, and suggest therapeutic treatment options.

Incidental finding of dysgeusia relieved by injections of botulinum toxin A.

OBJECTIVE: We report the unique finding of hemifacial spasm and associated dysgeusia that resolved after treatment with botulinum toxin A (BTX-A). STUDY DESIGN: Case report. METHODS: Three years after undergoing resection of an acoustic neuroma and subsequent resolution of postoperative left-sided facial nerve palsy, a 38-year-old woman presented with new onset of facial spasm and dysgeusia. RESULTS: After three courses of BTX-A injections during a 2-year period, symptoms of both facial spasm and dysgeusia resolved after treatments and returned between treatments. CONCLUSIONS: These findings, which have not been reported previously in the literature, indicate a potential role for BTX-A in the treatment of surgically associated dysgeusia.

Idiopathic dysgeusia; an open trial of alpha lipoic acid (ALA) therapy.

We selected two homogenous groups, each of 22 patients with idiopathic dysgeusia, an altered perception of taste, matched for age and sex, for an open trial of alpha lipoic acid compared with placebo. The 22 patients in the study group were treated with alpha lipoic acid for 2 months. The 22 patients in the control group were treated for 2 months with carboxymethylcellulose. The latter group was then treated with alpha lipoic acid for 2 months. The results showed significant symptomatic improvements compared with placebo, in both groups of patients with dysgeusia treated with alpha lipoic acid, suggesting that idiopathic dysgeusia may be a neuropathy comparable to the burning mouth syndrome.