Effect of Chemotherapy With Paclitaxel/Cisplatin on Development Dysgeusia in Non Small Cell Lung Cancer

Study Overview
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Brief Summary
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One of the most widely used treatments for non-small cell lung cancer (NSCLC) is the combination of paclitaxel-cisplatin. These drugs may contribute to taste alterations like dysgeusia. Which alters the feeding of cancer patients, contributing to the anorexia, weight loss and malnutrition, which leads to a prognostic impact in a lower patient response to chemotherapy, radiotherapy and surgical treatment as well as increased toxic effects, impacting treatment discontinuation and therefore, morbidity and survival of patients. The objective of this study is to describe the threshold of perception and recognition of basic tastes in patients with NSCLC before treatment with platin and paclitaxel-based chemotherapy and after the second cycle, and analyze the effect in the developement of dysgeusia, as well as the association between these and the nutritional status and quality of life.

Detailed Description
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Lung cancer is the leading cause of death from malignancies in our country. It was recently reported to induce 11.5% of cancer deaths in Mexico, with a rate of 6.5 per 100 000 people. Non-Small Cell Lung Cancer (NSCLC) accounts for 80% of all lung cancer cases. Less than 20% has resectable disease and in the National Cancer Institute of Mexico exclusively less than 2%, representing chemotherapy the standard of care in these patients. One of the most widely used drug combinations is paclitaxel-cisplatin. It has been reported a prevalence of malnutrition in 60 to 79% in this type of cancer, being the major contributor to morbidity and mortality. The etiology resides both in the systemic effects of the tumor and toxic effects of treatment as low levels hematologic, nausea, vomiting, mucositis, anorexia, dysgeusia, among others. Weight loss has a strong impact on the response to chemotherapy, radiotherapy and surgery, as well as increased toxic effects impacting the discontinuation of treatment and is considered an independent predictor of survival for most patients with NSCLC. Is estimated that over 20% of cancer patients the cause of death are inanition effects. Among the most frequent symptoms in advanced unresectable cancer or its treatment that may affect food intake and hence nutritional status, are the early satiety and dysgeusia (61% and 46% respectively). As are difficult to change early satiety, dysgeusia is a field for selecting strategies in its management. The dysgeusia is defined as a change in taste that can manifest as a distortion of taste, lack of taste (ageusia), decreased sensitivity of perception (hypogeusia) or increased sensitivity to some or all flavors (hypergeusia). The development of dysgeusia have clinical significance in the etiology of cancer anorexia because it can affect eating habits and contribute to weight loss or malnutrition and consequently affect the quality of life. The chemotherapy may contribute to dysgeusia. It has reported a prevalence of 56.3% of Dysgeusia in cancer patients under this type of treatment. As well, zinc deficiency has been associated with the hypogeusia, this metal to be involved at various levels in the physiology of the role of taste at various levels of cell several organization. Several studies have linked consumption dysgeusia with energy and macronutrients, weight loss, lack of appetite and early satiety. The type of tumor, stage, chemotherapy regimen and serum zinc levels are associated with dysgeusia, but the exact mechanism underlining these disturbances are not known at totality. No known if chemotherapy or before this is presented dysgeusia. In addition there are few studies in this area and with methodological weaknesses, among which include heterogeneous population (patients with a diagnosis of malignancy of breast, lung, prostate, multiple myeloma and lymphoma), different patterns of treatment(different chemotherapy drugs, radiotherapy schedules and combination of both forms of measurement of dysgeusia, besides the absence of dysgeusia baseline evaluation before chemotherapy to establish a causal association between chemotherapy and taste alteration. Also, is unknown if dysgeusia impact on body composition determined by bioelectrical impedance, phase angle in and consumption of micronutrients (iron, sodium, zinc, B6, B12). That's why is necessary to continue studying this phenomenon to develop a better understanding of the nature, frequency, severity and duration of dysgeusia in patients with advanced lung cancer, the role that zinc exerts in its development and its impact on consumption food, anthropometric parameters and quality of life in such patients before and after chemotherapy in the same regimen of chemotherapy.

Official Title
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Effect of Chemotherapy With Paclitaxel and Cisplatin on Development Dysgeusia in Non-small Cell Lung Cancer Patients

Conditions
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Dysgeusia, Non-Small Cell Lung Cancer, Taste Disorders, Lung Neoplasms, Small Cell Lung Carcinoma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients over 18 years old with INCan histopathological diagnosis of Lung Cancer Stage III or IV ECOG score ≤ 2 Candidates for first-line chemotherapy based 1 st Paclitaxel / cisplatin 200 mg/m2 and 75 every 3 weeks Signed informed consent (and ethical scientific committee No. (010/023 (IMO) (CB/618 Exclusion Criteria: Patients who withdraw their consent and not want to continue with the evaluation of the study Common cold or hay fever, recent dental procedure, evidence of gingival inflammation or infection or oral mucosa People diagnosed with epilepsy or some other neurological disorders associated Concomitant radiotherapy in head and neck.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| BASELINE<br>Outpatients from National Cancer Institute with stage III and IV NSCLC candidates for 1 st line chemotherapy paclitaxel-cisplatin based agreeing to participate in the study | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dysgeusia (UMAMI Perception) | Describe the threshold of perception and recognition (PT and RT, respectively) umami) with 5 dilutions with different concentrations. The patients were instructed to taste each 5 ml dilution in ascending order and to rinse the dilution around the entire oral cavity. After each rinse, the patients were asked whether the sample they took tasted different from water to identify their PT, which was assigned to the lowest concentration at which the subject perceived a difference in taste from water. If so, then the patients were asked to identify the taste to define their RT, which was assigned to the lowest concentration at which the subject identified the taste. | Change from Baseline in threshold of perception at 6 weeks | 
| Dysgeusia (UMAMI Recognition) | Describe the threshold recognition (RT) of umami with 5 dilutions with different concentrations. The patients were instructed to taste each 5 ml dilution in ascending order and to rinse the dilution around the entire oral cavity. After each rinse, the patients were asked whether the sample they took tasted different from water to identify their PT, which was assigned to the lowest concentration at which the subject perceived a difference in taste from water. If so, then the patients were asked to identify the taste to define their RT, which was assigned to the lowest concentration at which the subject identified the taste. | Change from Baseline in threshold of perception at 6 weeks | 
| Dysgeusia (SWEET Perception) | Describe the threshold perception (PT) of sweet taste with 5 dilutions with different concentrations. The patients were instructed to taste each 5 ml dilution in ascending order and to rinse the dilution around the entire oral cavity. After each rinse, the patients were asked whether the sample they took tasted different from water to identify their PT, which was assigned to the lowest concentration at which the subject perceived a difference in taste from water. If so, then the patients were asked to identify the taste to define their RT, which was assigned to the lowest concentration at which the subject identified the taste. | Change from Baseline in threshold of perception at 6 weeks | 
| Dysgeusia (SWEET Recognition) | Describe the recognition threshold (RT) of sweet taste with 5 dilutions with different concentrations. The patients were instructed to taste each 5 ml dilution in ascending order and to rinse the dilution around the entire oral cavity. After each rinse, the patients were asked whether the sample they took tasted different from water to identify their PT, which was assigned to the lowest concentration at which the subject perceived a difference in taste from water. If so, then the patients were asked to identify the taste to define their RT, which was assigned to the lowest concentration at which the subject identified the taste. | Change from Baseline in threshold of perception at 6 weeks | 
| Dysgeusia (BITTER Perception) | Describe the perception threshold (PT) of bitter taste with 5 dilutions with different concentrations. The patients were instructed to taste each 5 ml dilution in ascending order and to rinse the dilution around the entire oral cavity. After each rinse, the patients were asked whether the sample they took tasted different from water to identify their PT, which was assigned to the lowest concentration at which the subject perceived a difference in taste from water. If so, then the patients were asked to identify the taste to define their RT, which was assigned to the lowest concentration at which the subject identified the taste. | Change from Baseline in threshold of perception at 6 weeks | 
| Dysgeusia (BITTER Recognition) | Describe the recognition threshold (RT) of bitter taste with 5 dilutions with different concentrations. The patients were instructed to taste each 5 ml dilution in ascending order and to rinse the dilution around the entire oral cavity. After each rinse, the patients were asked whether the sample they took tasted different from water to identify their PT, which was assigned to the lowest concentration at which the subject perceived a difference in taste from water. If so, then the patients were asked to identify the taste to define their RT, which was assigned to the lowest concentration at which the subject identified the taste. | Change from Baseline in threshold of perception at 6 weeks | 
| Dysgeusia (UMAMI Dilutions Dichotomized) | We divide dilutions in two groups and dichotomized the patients into high and low sensibility to umami taste. (perception) | pre - post chemotherapy (6 weeks) | 
| Dysgeusia (SWEET Dilutions Dichotomized) | We divide dilutions in two groups and dichotomized the patients into high and low sensibility to sweet taste. | pre - post chemotherapy (6 weeks) | 
| Dysgeusia (BITTER Dilutions Dichotomized) | We divide dilutions in two groups and dichotomized the patients into high and low sensibility to umami, bitter and sweet tastes | pre - post chemotherapy (6 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BODY COMPOSITION | fat mass and lean body mass pre-post chemotherapy | Change from Baseline in perception and recognition thresholds at 6 weeks | 
| Body Mass Index | Body mass index, using the formula kg/m^2 | Change from Baseline in threshold of perception and recognition at 6 weeks | 
| Subjective Global Assessment | validated questionnaire to identify patients with malnutrition or risk of malnutrition Subjective global assessment (PG-SGA) was used to assess and classify patients as having severe or moderate malnourishment (B or C) or as being well nourished (A). | descriptive values before chemotherapy | 
| PROTEIN AND FAT Consumption | energy and nutrimental consumption was estimated by questionnaire SNUT difference between ≥ Sweet perception thresholds vs < Sweet perception thresholds after chemotherapy | participants were evaluated baseline and after 2 cycles of chemotherapy, an average of 6 weeks | 
| IRON Consumption | IRON consumption was estimated by questionnaire SNUT difference between ≥ Sweet perception thresholds vs < Sweet perception thresholds after chemotherapy | participants were evaluated baseline and after 2 cycles of chemotherapy, an average of 6 weeks | 
| Quality o f Life | The HRQL evaluation was assessed using the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaires specific for cancer and for LC (EORTC-QLQ-C30 and QLQ-LC13). [18, 19] Scores for the multi-item functional or symptom scales and the single items scales were calculated using a linear transformation of raw scores to produce a range from 0 to 100, as described by EORTC. A score of 100 represents the best score for the global health status and functional scales of QoL or 0 in the symptom rating. | participants were evaluated baseline and after 2 cycles of chemotherapy, an average of 6 weeks | 
| Change From Baseline in Albumin After 2 Cycles of Chemotherapy | comparison of patients who increased or decreased their sensibility to the PT of umami taste | participants were evaluated baseline and after 2 cycles of chemotherapy, an average of 6 weeks | 
| Peripheral Neuropathy (QLQ-C30 Version 3, EORTC) | comparison of peripheral neuropathy patients who increased or decreased their sensibility to the PT of umami taste The HRQL evaluation was assessed using the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaires specific for cancer and for LC (EORTC-QLQ-C30 and QLQ-LC13). Scores for the multi-item functional or symptom scales and the single items scales were calculated using a linear transformation of raw scores to produce a range from 0 to 100, as described by EORTC. A score of 100 represents the best score for the global health status and functional scales of QoL or 0 in the symptom rating. | participants were followed for the duration of 2 cycles of chemotherapy, an average of 6 weeks | 
| Global Status of Quality of Life (C-30,LC13 EORTC) | differences in global status of QoL scale (C-30,LC13 EORTC) between those with more or less sensibility to recognize the umami taste. score of scale 0-100, a higher score represents better overall state. | time between baseline and before 2 cycles of chemotherapy, an average of 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Small Cell Lung Cancer, Dysgeusia, Antineoplastic Combined Chemotherapy Protocols, Paclitaxel, Cisplatin