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The Oncologist, Vol. 13, No. 3, 337-346, March 2008; doi:10.1634/theoncologist.2007-0217
© 2008 AlphaMed Press

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Symptom Management and Supportive Care

Prevention of Docetaxel- or Paclitaxel-Associated Taste Alterations in Cancer Patients with Oral Glutamine: A Randomized, Placebo-Controlled, Double-Blind Study

Florian Strassera, Ruth Demmera, Christel Böhmea, Shu-Fang Hsu Schmitzc, Beat Thuerlimanna,b, Thomas Cernya, Silke Gillessena

aDivision of Oncology/Haematology, Department of Internal Medicine, and bSenology Centre, Department of Interdisciplinary Medical Services, Cantonal Hospital, St. Gallen, Switzerland; cStatistical Unit, Swiss Group for Clinical Cancer Research, Bern, Switzerland

Key Words. Glutamine • Paclitaxel • Docetaxel • Taste alterations • Neuropathy • Prevention

Correspondence: Florian Strasser, M.D., A.B.H.P.M., Oncology and Palliative Medicine, Division of Oncology/Haematology, Department of Internal Medicine and Palliative Care Centre, Cantonal Hospital, Rorschacherstrasse, 9007 St. Gallen, Switzerland. Telephone: 41-71-494-1111; Fax: 41-71-494-6425; e-mail: florian.strasser{at}kssg.ch or fstrasser{at}bluewin.ch

Received November 2, 2007; accepted for publication January 15, 2008.

Disclosure: The article discusses glutamine manufactured by Baxter for prophylaxis of taste alterations. No other potential conflicts of interest were reported by the authors, planners, reviewers, or staff managers of this article.


   Learning Objectives
Top
 Footnotes
 Learning Objectives
Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 Conclusion
 Acknowledgments
 References
 
After completing this course, the reader will be able to:

  1. Discuss the frequency, clinical presentation, and patient burden of taste alterations and peripheral neuropathy in patients receiving taxane-based chemotherapy.
  2. Identify the risk factors for developing peripheral neuropathy and taste alterations associated with taxanes.
  3. Administer glutamine treatment in the supportive care of peripheral neuropathy and taste alterations and evaluate emerging new agents.

Access and take the CME test online and receive 1 AMA PRA Category 1 CreditTM at CME.TheOncologist.com


   ABSTRACT
Top
 Footnotes
 Learning Objectives
 Abstract
Introduction
 Patients and Methods
 Results
 Discussion
 Conclusion
 Acknowledgments
 References
 
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 ≤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.


   INTRODUCTION
Top
 Footnotes
 Learning Objectives
 Abstract
 Introduction
Patients and Methods
 Results
 Discussion
 Conclusion
 Acknowledgments
 References
 
Taxanes inhibit disassembly of microtubules, which play an important role in mitosis and axoplasmatic transport, and can cause degeneration of peripheral, mainly small sensory, nerves [1]. Peripheral neuropathy develops with both paclitaxel and docetaxel with a dose-dependent reduction in nerve conduction velocity, but as the pathological changes are milder than expected on the basis of neurophysiological results, the neurotoxic effects of taxanes seem to be mediated not only by mictrotubular damage, but also by other targets [2].

Risk factors for polyneuropathy include dose per cycle, treatment schedule (more neurotoxicity with weekly than 3-week schedules [3]), duration of infusion (duration of the time of total paclitaxel above a concentration of 0.05 µmol/l), and cumulative dose [4]. Age may [4] or may not [5] be a risk factor. A typical syndrome of neuropathy develops, including painful paresthesias, global areflexia, and distal weakness, in a predictable temporal pattern of early onset, length-independent and progressive sensory defect, and delayed distal and length-dependent motor deficits [6].

Taste alterations occur in up to two thirds of patients treated with paclitaxel and docetaxel [7]. The mechanism by which taxanes cause taste alterations is understood as neurological damage [8], rather than an isolated problem of saliva, occurring in the context of radiation treatment [9]. But taste alterations are not included in the Function Assessment of Cancer Therapy–Taxane, which focuses mainly on neuropathy and fluid retention [10].

In clinical trials of systemic anticancer treatment, taste alterations (dysgeusia) are rarely assessed prospectively but are reported only in toxicity scales: namely, under gastrointestinal complications and symptoms (grades 1–2), salivary gland changes, and cranial neuropathy (cranial nerve VII, grades 0–5) [11]. To report dysgeusia as neuropathy, the cranial nerves (VII, IX, X) must be documented, as gustatory information from the taste buds is carried by specific branches of three, not only one, cranial nerves [8]. Grade 1–2 toxicities are reported in many clinical trials in a summative way, carrying the risk of underreporting the "true burden" of taste alterations [12]. Patients' experiences, including subjectively relevant complications, are detected substantially later through adverse-events reporting rather than through assessment of patients' perceived symptoms and quality of life measures [13]. An example from North Central Cancer Treatment Group investigations is that adverse-events detection missed >50% of peripheral neuropathy identified through quality-of-life data [14].

Taste alterations are also associated with stomatitis [15], zinc deficiency [8], and antineoplastic agents other than taxanes, specifically cisplatin and doxorubicin [12]. Taste alterations are also frequent (60%) in far-advanced cancer patients without anticancer treatment [16]. Taste alterations can impair patients' quality of life [17] and decrease appetite and nutritional intake [18], leading to involuntary weight loss and ultimately malnutrition [19]. Currently, no standard treatment has been established to alleviate taste alterations caused by cytotoxic drugs [20]. In a pilot study, zinc supplementation for patients during radiation therapy improved taste significantly more than placebo [21], but these results were not confirmed in a larger phase III trial [22].

Glutamine is vital for several physiologic functions, such as nitrogen transfer between tissues and synthesis of RNA, DNA, and some neurotransmitters [23]. Preclinical data show amelioration of vincristine [24], cisplatin, and paclitaxel [25] associated sensory and motor neuropathy by glutamine in rats. The daily intake of glutamine in healthy persons is <10 g, whereas cancer patients may require higher doses because of an often accelerated metabolism and a decreased body pool of glutamine [26], as other amino acids decrease during severe illness [27, 28]. However, an association of glutamine blood level or quantitative glutamine metabolism with taste alteration is not reported.

The clinical use of glutamine is supported by grade B recommendations for multiple-trauma and critically ill patients (to improve immunological aspects and clinical outcomes), and for cancer patients undergoing (high-dose) chemotherapy (to improve mucositis and recovery time) [23, 29]. In cancer patients with taxane chemotherapy, few trials with glutamine have been reported. The prevention of peripheral neuropathy associated with high-dose paclitaxel was investigated in 50 patients with metastatic breast cancer in a sequential cohort study without (n = 33) and with (n = 12) oral glutamine (10 g three times a day [t.i.d.]). The severity of sensory and motor neuropathy was significantly reduced by glutamine, as were associated functional outcomes [30]. A later phase II trial by the same research group in the same population confirmed the results [31]. In contrast, paclitaxel-induced myalgias and arthralgias were not less frequent with the administration of 30 g oral glutamine as compared with placebo [32]. Clinical trials specifically tackling taste alterations or investigating docetaxel have not been not reported. The application of glutamine has been reported to be safe; a transient increase in uric acid and creatinine, associated with fluid intake, occurs with glutamine given i.v. or orally at doses up to 0.34 g/kg [33, 34]. The tumor response rate to paclitaxel seems not to be changed by glutamine [35].

The aim of this longitudinal trial was to compare the effects of 6 weeks of supplementation using oral glutamine with those of placebo on the prevalence and severity of taste alterations in cancer patients receiving first-time taxane-based chemotherapy.


   PATIENTS AND METHODS
Top
 Footnotes
 Learning Objectives
 Abstract
 Introduction
 Patients and Methods
Results
 Discussion
 Conclusion
 Acknowledgments
 References
 
This single-center, randomized, double-blind, placebo-controlled, two-arm, parallel study adhered to good clinical practice (GCP) and the Declaration of Helsinki, and was approved by the local ethical review board and the federal health authorities.

Participants
Physicians recruited adult patients with cancer who were receiving, for the first time, a taxane-containing chemotherapy from March 2004 to March 2006 in the outpatient and inpatient oncology wards. Eligible patients gave written informed consent to participate, could feed themselves, had an Eastern Cooperative Oncology Group performance status score ≤2, had no previous surgery or radiation therapy of the oral or nasal region, had no oral candidiasis, had no zinc deficiency (measured at baseline; patients with zinc deficiency received supplementation of 15 mg oral zinc t.i.d.), and had a creatinine clearance of ≥30 ml/minute (Cockgroft-Gault).

Intervention
On the first day of taxane-based chemotherapy, patients received a 4-week supply of glutamine (Pure Powder; Baxter AG, Volketswil, Switzerland) or maltodextrin (Baxter, Switzerland) as placebo. Patients took 30 g/day in 2–3 doses for the duration of the taxane-based chemotherapy, at least 2 months. They documented their daily intake in a diary and returned the boxes at the end of each cycle. Glutamine and maltodextrin were indistinguishable white powders dissolved in fluids (i.e., water, juice, soup, yogurt).

Objectives
We tested the hypothesis that patients with first-time taxane-based chemotherapy given preventative therapy with oral glutamine would have significantly fewer patient-perceived and objective taste alterations than patients taking placebo.

Outcome Measures
Assessments were done at baseline, on day 1 of each cycle, and on day 8 of the second chemotherapy cycle, including objective and subjective tests for taste qualities, physical examination and mouth inspection, neuropathy screening, body weight assessment, and adverse-event reporting. Patients reported taste daily during the whole study period.

The primary outcome was dysgeusia, reported daily by the patient at the same time (usually before dinner) by answering the question: "Presently my sense of taste is ... " using a visual analogue scale (VAS) (0 mm, very good; 100 mm, very bad). Test-retest reliability in 26 cancer patients from a pilot study [36] was satisfactory (mean, 56 mm and 55 mm; standard deviation [SD] 18 and 20; Pearson correlation, 0.52; p = .006).

For the objective taste recognition test (gustatory testing), four different cottonwood tips soaked with 1% chinin (bitter), 10% citric acid (sour), 10% saline (salty), and sugar water (sweet) [37] were applied in random order to the tongue of the patient, who was allowed to keep it in his/her mouth for comfort. Chinin was applied on the back of the tongue, whereas citric acid, saline, and sugar water were applied on the sides of the tongue. The patient had to recognize the taste correctly (yes/no). The subjective test perception assessment included four category scales (normal, increased, decreased some, decreased a lot) for the four taste items. These items were piloted previously [36].

Adverse events were classified according to Common Toxicity Criteria [11]; neuropathy, stomatitis/mucositis, and arthralgia/myalgia were given special attention in physical examinations.

Zinc deficiency was assessed through blood levels [21] at baseline and on the first day of every chemotherapy cycle, and patients were treated with 15 mg zinc t.i.d. if their levels were below normal.

Sample Size
Sample size was calculated with reference to a pilot study evaluating items for taste assessment [36]. Half the SD (18–20 mm) of the taste VAS may be considered clinically significant [38].

Treatment Assignment, Randomization, and Blinding
Patients were randomized before taxane-based chemotherapy: unique patient numbers were assigned continuously and corresponded to the randomization number. Identical boxes containing glutamine or maltodextrin were labeled before the study start with randomization numbers. The randomization list was prepared by an independent person and was kept inaccessible to the study team in a locked container. Sealed envelopes for each number were stored in a locked container accessible to clinicians for emergencies, as required by GCP standards.

The database was closed after completion of the study and rating of all adverse events. Thereafter, an independent senior faculty member (Ph.D.) in laboratory medicine who had controlled the randomization procedure revealed the treatment assignments.

Statistical Analyses
Patient characteristics and outcome variables are summarized by either frequency counts or descriptive statistics.

For primary outcomes, repeated dysgeusia scores were analyzed with a linear mixed model including group, baseline dysgeusia score, and time interval from baseline as covariates, with a power serial correlation structure. The difference between the baseline average dysgeusia and the maximum (worst) dysgeusia under treatment was compared using the Wilcoxon two-sample test.

Repeated binary values of each objective taste item were analyzed with a generalized estimating equation using the logit link function, including group and baseline value as covariates, with an independent working correlation structure. Repeated ordinal values of each subjective taste item were analyzed with a generalized estimating equation using a cumulative logit link function, including group and linear time effect (day) as covariates, with an independent working correlation structure.

Toxicities were compared using Fisher's exact test.


   RESULTS
Top
 Footnotes
 Learning Objectives
 Abstract
 Introduction
 Patients and Methods
 Results
Discussion
 Conclusion
 Acknowledgments
 References
 
Patients
Patient characteristics (Table 1), the percentage of dropouts, and the reasons for dropout were similar between treatment arms (Fig. 1). Of 52 patients randomized, two patients did not continue taxane therapy after the first application, one patient was not willing to take the powder formula of the study-drug, and two patients withdrew consent (one because of nausea and vomiting after the first taxane application and one because of too much burden with tumor therapy). Of 47 patients receiving at least one day of study treatment, three men with advanced lung cancer experienced rapid tumor-related deterioration or associated complications (hospitalization for pneumonia, pain) and died after 1, 3, and 4 weeks, respectively. Three men (two with lung cancer and one with prostate cancer) withdrew consent to comply with the study procedures and did not complete outcome measurements. In addition, one had painful bone metastasis, one had depression, and one had early satiety and fullness. In the first 3 weeks, four patients having glutamine stopped treatment—two (gastric cancer, pancreatic carcinoma) because of taxane toxicity, one (prostate cancer) because of nausea, and one (cervical carcinoma) withdrew consent to continue; one patient receiving placebo stopped as a result of bloating. In weeks 4–6, three patients stopped glutamine treatment—two women with advanced breast cancer (one because of diarrhea and abdominal pain and one for personal reasons) and one man with advanced prostate carcinoma (because of vomiting). Likewise, three patients receiving placebo stopped—one man (gastric cancer) because of frequent, physically deteriorating travel, one man (neoadjuvant) because of bloating, vomiting, and burning, and one man (adjuvant) because of new information in newspapers about treatment for lung cancer. Forty-one patients complied with the study procedures, completing the diary for the primary outcome and the medication log, and were analyzed.


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  		Table 1. Demographics of patients receiving glutamine or placebo

 


Figure 1
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  		Figure 1. Patient flow.

 
The median study duration was 11 weeks for both glutamine (range, 1–33) and placebo (range, 2–28). The median total dose of study drug per patient was 1,430 g for glutamine (range, 70–6,110) and 2,175 g for placebo (range, 50–5,760).

At baseline, six patients in the glutamine arm had a pre-existing neuropathy (four grade 1, two grade 2 because of degenerative changes of the vertebrae); in the placebo arm four patients had grade 1 pre-existing neuropathy.

Before the study, two patients received platins (one in the glutamine arm and one in the placebo arm) and one received vinca alkaloids (in the glutamine arm).

The median zinc values (normal, 11–18 µmol/l) at baseline were 11.2 µmol/l for patients in the glutamine arm (range, 8–18) and 9.9 µmol/l for patients in the placebo arm (range, 7–14); two patients in each arm received supplementation. Two patients treated with glutamine and none treated with placebo were treated for oral candidiasis.

Dysgeusia
Of 41 patients, 35 (85%) experienced higher than baseline dysgeusia. On average, a mean VAS increase from 11/100 mm at baseline to 37/100 mm at maximum was observed, signifying worse dysgeusia, with no differences between the glutamine (maximum, 41.2/100 mm) and placebo (maximum, 34.1/100 mm) arms. The median values are reported in Table 2.


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  		Table 2. Difference between the baseline dysgeusia and the maximum (worst) dysgeusia under taxane treatment in patients receiving either glutamine or placebo

 
Daily dysgeusia scores were not different for glutamine and placebo. Of 2,834 observations, no significant group effect between glutamine and placebo could be detected with the linear mixed model (coefficient, –2.4; empirical standard error [SE], 2.9; p = not significant). There was a significant baseline dysgeusia effect (coefficient, 0.7; SE, 0.08; p < .0001), but a subgroup analysis (cutoff, 11 mm) did not change the result of a missing group effect between glutamine and placebo. No significant linear time effect (day) could be detected (coefficient, 0.005; SE, 0.03; p = not significant).

Objective Recognition of Taste Qualities
No differences between glutamine and placebo were detected for objective taste recognition. There was no baseline effect. At day 8 of the second chemotherapy cycle, 13 patients taking glutamine and 14 taking placebo had a taste test. On that day, 12 of 13 patients taking glutamine had the same taste recognition for bitter as at baseline (one patient did not recognize it at baseline but did recognize it at day 8; no patient recognized it at baseline but not at day 8); the corresponding values were nine for sour (2, 2), eight for salty (1, 3; 1 missing), and 13 for sweet; for the placebo group, the corresponding values were 14, 9 (3, 2), 9 (2, 2), and 13 (0, 1) for the four tastes, respectively.

Subjective Perception of Taste Items
The generalized estimating equation model for repeated measures of subjective taste items revealed no significant group effect for glutamine and placebo, for either bitter (147 observations; coefficient, 0.40; SE, 0.73), sour (146 observations; coefficient, 0.93; SE, 0.64), salty (147 observations; coefficient, 0.41; SE, 0.63), or sweet (146 observations; coefficient, –0.50; SE, 0.59).

Likewise, no linear time effect (day) was detected for any taste item: bitter (coefficient, 0.0057; SE, 0.006), sour (coefficient,: –0.0006; SE, 0.005), salty (coefficient, 0.0015; SE, 0.0041), or sweet (coefficient, 0.009; SE, 0.005).

No baseline effect was detected for bitter or sour. For sour and sweet, all baseline values were the same among all evaluable patients impeding inclusion in the model.

Toxicities: Adverse Events
Twenty-two of 41 patients (12 in the glutamine group and 10 in the placebo group) developed peripheral neuropathy grade 1 or 2, none developed grade 3. Grade 2 toxicity was significantly (p = .048) more frequent in glutamine than in placebo patients (Table 3). Of the patients with pre-existing neuropathy treated with glutamine, the patient with grade 2 and one of the patients with grade 1 at baseline improved, one had no follow-up evaluation, and one finally developed finally grade 2 neuropathy in cycle 6. Of the patients treated with placebo, two deteriorated to grade 2, one remained unchanged, and one improved transiently (grade 1 at cycle 6).


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  		Table 3. Comparison of adverse events, as defined by Common Toxicity Criteria (grade 0 and 1 versus grade ≥2), between patients receiving glutamine and those receiving placebo

 
More patients experienced grade 2 nausea with glutamine (four grade 0, 10 grade 1, seven grade 2) than with placebo (11 grade 0, 8 grade 1, one grade 2).

Body Weight
There was no difference in body weight changes during the study period between glutamine and placebo patients.


   DISCUSSION
Top
 Footnotes
 Learning Objectives
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
Conclusion
 Acknowledgments
 References
 
This is the first prospective study investigating glutamine for the prevention of taste alterations associated with taxane-based chemotherapy and reporting the frequency of both subjective and objective taste alterations. Compared with placebo, oral glutamine at the dose given did not result in lower incidences of subjective taste disturbances or altered taste perception.

The patients in our study did develop taste alterations during taxane-based chemotherapy, in a range (85% higher than baseline) comparable with ranges seen in prior studies [7] and of sufficient effect size (average increase from 11/100 to 37/100) to detect a clinically relevant difference between glutamine and placebo. The frequency of peripheral neuropathy in our study population seems representative of taxane-based chemotherapies in a mixed population [4].

Our chosen dose of 30 g/day in patients with a mean weight of 71 kg, controlled by patient diaries and measurement of remaining drug in returned bottles, is consistent with reported doses from other trials in cancer patients, using 0.34–0.4 g glutamine/kg per day [39, 40], a total dose of 18 g [41], or 15 g twice daily [42]. Higher doses were also reported in a randomized, placebo-controlled, within-patient crossover trial in pediatric oncology, where patients did not detect a reduction in mucositis; however, in the glutamine phase, patients required less parenteral nutrition [43]. The preceding dose escalation was designed mainly for tolerability and safety (ammonium blood levels) but not dose-dependent efficacy [44].

Our patients receiving glutamine had, at baseline, lower performance status scores and a higher frequency of weight loss than patients receiving placebo. An association between taste changes and weight loss in patients with advanced cancer was recently reported [19]. However, our groups were balanced for taste alterations at baseline.

In our patients, peripheral neuropathy was more severe (more grade 2) in patients receiving glutamine than in those receiving placebo. This finding contrasts with 12 patients [30] and 17 patients [31] receiving glutamine for neuroprotection during high-dose paclitaxel treatment, who reported fewer symptoms and signs associated with peripheral neuropathy than control patients not receiving glutamine, but both trials were not randomized and used no placebo control. Comparison with our patients may require caution as they received standard-dose taxane treatment, both paclitaxel and docetaxel, and most were treated with weekly schedules. Glutamine prevention during high-dose paclitaxel treatment did not significantly protect from loss of sensory or motor nerve conduction, but only from symptoms and signs of peripheral neuropathy [31]. Glutamine prevention during oxaliplatin treatment significantly reduced peripheral neuropathy but not electrophysiological alterations [42]. We and others [30, 31] did not assess blood levels of nerve growth factor, which would be expected to be lower in patients suffering from severe neurotoxicity [45]. Glutamine degradation yields ammonia and glutamate, both known to be neurotoxic; however, in many studies exploring glutamine safety, no neurological adverse effects were reported [34].

We did assess a subjective taste sensation, which is a summation of various taste qualities. Theoretically, this approach may underestimate the effects and the prevention by glutamine of specific taste qualities by taxanes. Our patients had a more consistent recognition of bitter and sweet than of salty and sour, a yet unreported observation in cancer patients. Patients may also experience a preventive effect on flavor, a combined sensation of taste and smell [17]; however, evidence of specific, not global, effects on taste qualities or smell by taxanes is lacking as are data to support patients' inability to perceive such effects by a global taste experience.

Some features of our trial call for cautious interpretation. We included a mixed cancer patient population with the risk that subgroups may have profited from the intervention, namely, patients receiving higher doses of paclitaxel [30, 31]. Associated with our "real world" population is the relatively high number of patients (22 of 52) not reaching the first time point for per protocol analysis. In our relatively small trial, we did not see a true clinical effect favoring glutamine, the between-group differences in dysgeusia relative to baseline (delta, 3 mm; SD, 20 and 26) even point in the opposite (wrong) direction. To detect such a small difference in the desired direction would require 860 patients per group for an 80% power and a 5% type I error rate, with a common SD of 25. Another limitation is that we explored prevention, not early treatment, of taste alterations; it can be hypothesized that treatment would be more efficient. The primary outcome chosen, even though not used as extensively as other symptom outcome instruments, seemed to be sensitive in detecting clinically relevant changes, as the increase in patients' perceived taste alterations during taxane-based chemotherapy shows. The unbalanced early stopping of the study medication may have contributed to the negative results.

Our study does not support the clinical use of glutamine prophylaxis for taste alterations in patients receiving taxane-based chemotherapy.

Further research to alleviate taste alterations is clearly justified acknowledging the patient's burden [7, 17]. In clinical practice, the true treatment burden of taste alteration and its impact on oral intake and physical function merit routine monitoring. Simple instruments, such as those used in this trial, may be implemented. Other substances may be tested, as explored for supportive care of neuropathy or mucositis; they include new formulations of glutamine (powder in UpTecTM: Saforis®; MGI Pharma, Inc., Bloomington, MN) [46], recombinant human leukemia inhibitory factor [47], vitamin E [48], L-carnitine [49], erythropoietin [50], and antiangiogenic agents [51]. However, the question remains whether taste alterations are indeed a form of neuropathy or are caused partially by other mechanisms.


   CONCLUSION
Top
 Footnotes
 Learning Objectives
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 Conclusion
Acknowledgments
 References
 
Oral glutamine at the dose given did not result in a lower incidence of subjective taste disturbances or altered taste perception associated with taxane-based chemotherapy as compared with placebo. The current data, including our results, do not support the use of glutamine in the supportive care of taxane-associated dysgeusia.


   ACKNOWLEDGMENTS
Top
 Footnotes
 Learning Objectives
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 Conclusion
 Acknowledgments
References
 
This report represents original work designed, performed, analyzed, and reported by the authors.

Final results of the study were presented at the American Society for Clinical Oncology 2007 Annual Meeting in Chicago, Illinois, in the general poster session: Strasser F, Demmer R, Boehme C et al. Prophylactic oral glutamine for docetaxel- or paclitaxel-associated taste alterations in cancer patients: A randomized, parallel, placebo-controlled, double-blind study.

We thank our patients for participating in this trial, the nurses of the outpatient and inpatient oncology units of the department of oncology and the senology center for supporting the conduct of the trial, Kasia Galeka for voluntary editorial review, and Susan Eastwood, E.L.S. (D.), for her editorial assistance.

This trial is registered at the International Standard Randomized Controlled Trial Number (ISRCTN) Register (http://www.controlled-trials.com/ISRCTN18939629).

We are thankful for the academic research funding and limited unrestricted industrial support. We acknowledge the following research support: Swiss Institute of Applied Cancer Research (SIAK), pilot development grant; Eastern Switzerland Foundation of Clinical Cancer Research (OSKK); Baxter Switzerland, unrestricted grant and study medication free of charge; Bristol-Myers Squibb Switzerland, unrestricted grant.


   FOOTNOTES
 
Conception/design: Florian Strasser, Ruth Demmer, Christel Böhme, Shu-Fang Hsu Schmitz, Beat Thuerlimann, Thomas Cerny, Silke Gillessen

Financial support: Thomas Cerny

Administrative support: Beat Thuerlimann, Thomas Cerny

Provision of study materials or patients: Florian Strasser, Beat Thuerlimann, Thomas Cerny, Silke Gillessen

Collection/assembly of data: Florian Strasser, Ruth Demmer, Christel Böhme, Beat Thuerlimann, Thomas Cerny, Silke Gillessen

Data analysis and interpretation: Florian Strasser, Ruth Demmer, Christel Böhme, Shu-Fang Hsu Schmitz, Beat Thuerlimann, Thomas Cerny, Silke Gillessen

Manuscript writing: Florian Strasser, Ruth Demmer, Christel Böhme, Shu- Fang Hsu Schmitz, Beat Thuerlimann, Thomas Cerny, Silke Gillessen

Final approval of manuscript: Florian Strasser, Ruth Demmer, Christel Böhme, Shu-Fang Hsu Schmitz, Beat Thuerlimann, Thomas Cerny, Silke Gillessen


   REFERENCES
Top
 Footnotes
 Learning Objectives
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 Conclusion
 Acknowledgments
 References
 

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