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Nutritional support for patients with metastatic cancer
van der Werf, A.
2019
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van der Werf, A. (2019). Nutritional support for patients with metastatic cancer.
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Chapter 9
Taste alterations during treatment with protein kinase
inhibitors: a pilot study
Anne van der Werf
Marian A.E. de van der Schueren Maria Rovithi
Mariette Labots Sayed M.S. Hashemi Jacqueline A.E. Langius Henk M.W. Verheul
Introduction
Protein kinase inhibitors (PKIs) have caused a major survival improvement for patients with certain advanced cancers, like renal cell carcinoma and lung cancer. Due to increased clinical use of these agents, physicians are faced with a new spectrum of toxicities.1 One of the most common toxicities is patient-reported taste alterations,
which may impair nutritional intake and quality of life.1-3
While taste alterations induced by chemotherapy are caused via damage to rapidly dividing taste and smell receptor cells, xerostomia or oral mucositis,3 the pathobiology of PKI-induced taste alterations remains elusive.
A different pathobiology compared to chemotherapy-induced taste alterations is expected, because PKIs have a totally different mechanism of action and induce other manifestations of oral side-effects.1 Potential causes
include functional changes in taste or smell perception as a consequence of decreased taste- or smell receptor cell renewal, altered receptor function or interference with intracellular signaling pathways. However, it is unknown whether objective changes in taste or smell function occur in patients reporting subjective taste alterations. This pilot study describes patient-reported taste alterations during PKI treatment. In addition, the association between these patient reported taste alterations and potential causal factors – which has never been studied before – was evaluated.
Methods
Patients were eligible for inclusion in the study if they were diagnosed with metastatic cancer, starting treatment with a standard dose PKI, were over 18 years of age, had no comorbidities that are known to affect taste or smell and had not experienced taste changes due to previous treatment with chemo- or radiotherapy. All patients gave written informed consent and the study was approved by the Medical Ethics Committee of the VUmc. Assessments were done just before and at least 2 weeks after start of PKI treatment, the exact timing depended on the scheduling of the regular follow-up hospital visit.
taste qualities salty, sweet, sour and bitter.4 The test-retest correlation coefficient for this test is 0.68.4 The taste
strips were presented to the patient in increasing concentrations and in a randomized order of the taste qualities at each of the four concentration levels. For each taste strip the patient was asked to determine whether a salty, sweet, sour or bitter taste or no taste at all was identified, resulting in a score from 0 to 4 per taste quality and a total score of 0 to 16.
Smell function was objectified using Sniffin’ sticks (Burghart, Wedel, Germany). These Sniffin’ sticks are pen-like odor dispensing devices to determine smell threshold, discrimination and identification using a forced choice procedure.5 The test-retest correlation coefficients are 0.61 for threshold, 0.54 for discrimination, 0.73 for
identification and 0.72 for total smell score.5 The threshold score was determined with sixteen triplets of pens.
Each triplet contained one pen with a specific dilution-ratio of n-butanol, which had to be identified by the patient. Discrimination testing also comprised sixteen triplets of pens. Of each triplet, including two pens with the same smell and one pen with a different smell, the patient was asked to identify the pen with a different smell. Identification was scored using a 4-option multiple choice task for 16 common smells. The range for each smell subscore was 0 to 16 and the total smell score was defined as the sum of the three subscores.
Taste and smell changes between baseline and follow-up measurements were evaluated with Wilcoxon Signed Rank Tests. The mean changes in taste and smell scores between patients with versus without a reported taste sensation were compared with independent t-tests. A p-value below 0.05 was regarded statistically significant.
Results
reported a decreased taste function had a decrease of 4 points (maximum possible) for salty taste. These patients were both treated with sunitinib and described their taste change as ‘savory foods are less tasty’ and ‘no salty taste perception’. In the total group, objective smell scores did not change, neither did symptoms of a dry and painful mouth. However, patients reporting a decreased taste sensation had significantly more change in painful mouth score during PKI treatment than patients without taste alteration (+0.9 vs. -0.1, p=0.011, table 1). Of note, there were no relevant changes in smoking habits or use of co-medication during the study period.
Discussion
Table 1 – Taste and smell function before PKI treatment and change after 2-6 weeks of PKI treatment
All (n=18)¥ Patient-reported taste sensation (n=15)*
Not altered (n=7) Decreased (n=8)
Test scores Range Baseline score ∆ score ∆ score ∆ score
Tastetotal 0-16 8.5 [7.0, 11.0] +0.6 (2.5) +1.1 (1.8) +0.5 (2.9) Salt 0-4 3.0 [2.0, 4.0] -0.5 (1.6) +0.1 (1.1) -1.1 (2.0) Sour 0-4 2.0 [1.0, 3.0] +0.2 (1.1) +0.3 (1.0) +0.3 (1.3) Sweet 0-4 3.0 [1.0, 3.0] +0.3 (1.0) +0.3 (1.0) +0.5 (0.8) Bitter 0-4 2.0 [1.0, 3.0] +0.6 (1.1) † +0.4 (1.1) +0.9 (1.1) Smelltotal 0-48 28.8 [26.5, 33.0] -1.2 (5.3) -3.4 (6.5) +0.2 (4.6) Threshold 0-16 4.9 [4.5, 5.5] -0.4 (2.8) -1.6 (2.6) +0.6 (3.2) Discrimination 0-16 11.0 [9.0, 13.0] -0.2 (3.0) -1.1 (3.9) 0.0 (2.4) Identification 0-16 12.5 [11.0, 14.0] -0.6 (2.8) -0.6 (3.5) -0.4 (2.8) Symptoms Dry mouth 0-3 1.0 [0.0, 2.0] +0.1 (1.2) +0.1 (0.9) +0.3 (1.5) Painful mouth 0-3 0.0 [0.0, 0.0] +0.3 (0.8) -0.1 (0.4)‡ +0.9 (0.8) ‡
Baseline score is presented as median [interquartile range] and change in score is presented as mean (standard deviation). Higher scores for taste and smell indicate better taste/smell function, higher scores for symptom scores represent more symptomatology.
¥ includes patients without reported taste alteration (n=7) and with a reported decreased (n=8), increased (n=1) or altered
(n=2) taste sensation
*patients with an increased (n=1) or altered (n=2) taste sensation were excluded
† Significant increase in bitter score during treatment in the total study population (p=0.045)
‡ Significant difference in change of painful mouth score during treatment between patients without a reported taste
PKI-induced patient-reported taste alterations had a prevalence of 61%. During PKI treatment there was an overall objectified increase in bitter taste sensitivity. An increased bitter sensitivity negatively influences taste preferences and may be perceived as a decreased taste sensation.6 The change in bitter taste sensitivity might
be explained by an interaction with the G-protein-coupled bitter receptor, because protein kinases have known interactions with G-protein-coupled receptors.2,7 No other changes in taste or smell function were objectified
during PKI treatment. In contrast, treatment with chemotherapy has shown to significantly decrease objective taste and smell scores.8,9 This may be explained by the different mechanism of action of these anticancer agents.
Patient-reported taste alterations were not confirmed by objective changes in taste or smell function. Because the sense of taste is often confused with flavour – a combined sensation resulting from taste, smell, temperature and tactile information 2 – patient-reported and objective taste and smell function may not always correspond.10
Alternatively, the used tests may have limited sensitivity to detect small changes in taste and smell. Since there are no gold standard test for taste and smell, further development of adequate measures are eagerly awaited.3
The only factor associated with a patient-reported decreased taste sensation was a painful mouth, which is an indicator of oral mucositis. Oral mucositis might alter taste sensation without changing objective taste sensitivity, for instance by mucositis related formation of compounds which may cause off-flavor taste perceptions.6
In conclusion, this exploratory study shows a high prevalence of patient-reported taste alterations during PKI treatment. Patient-reported taste alterations were not related to objective changes of taste or smell scores or to a dry mouth, but were related to a painful mouth, an indicator of mucositis. Future research is needed to develop more adequate methods to objectify taste and smell function. In addition, the factors contributing to patient-reported taste alterations during PKI treatment should be studied in a larger cohort, preferentially during treatment with the same PKI, in order to develop potential interventions to reduce or prevent this toxicity.
Conflict of interest
The authors declare no conflicts of interest .
References
1. Vigarios E, Epstein JB, Sibaud V. Oral mucosal changes induced by anticancer targeted therapies and immune checkpoint inhibitors. Support Care Cancer 2017; 25(5): 1713-39.
2. van der Werf A, Rovithi M, Langius JAE, de van der Schueren MAE, Verheul HMW. Insight in taste alterations during treatment with protein kinase inhibitors. Eur J Cancer 2017; 86: 125-34.
3. Spotten LE, Corish CA, Lorton CM, et al. Subjective and objective taste and smell changes in cancer. Ann Oncol 2017;
28(5): 969-84.
4. Mueller C, Kallert S, Renner B, et al. Quantitative assessment of gustatory function in a clinical context using impregnated "taste strips". Rhinology 2003; 41(1): 2-6.
5. Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G. 'Sniffin' sticks': olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses 1997; 22(1): 39-52. 6. Hong JH, Omur-Ozbek P, Stanek BT, et al. Taste and odor abnormalities in cancer patients. J Support Oncol 2009;
7(2): 58-65.
7. Gavi S, Shumay E, Wang HY, Malbon CC. G-protein-coupled receptors and tyrosine kinases: crossroads in cell signaling and regulation. Trends Endocrinol Metab 2006; 17(2): 48-54.
8. Steinbach S, Hummel T, Bohner C, et al. Qualitative and quantitative assessment of taste and smell changes in patients undergoing chemotherapy for breast cancer or gynecologic malignancies. J Clin Oncol 2009; 27(11): 1899-905.
9. Boltong A, Aranda S, Keast R, et al. A prospective cohort study of the effects of adjuvant breast cancer chemotherapy on taste function, food liking, appetite and associated nutritional outcomes. PLoS One 2014; 9(7): e103512. 10. Soter A, Kim J, Jackman A, Tourbier I, Kaul A, Doty RL. Accuracy of self-report in detecting taste dysfunction.
