Receiving Cisplatin Chemotherapy Research Articles

A retrospective audit of audiology encounters in patients undergoing Cisplatin treatment at a large Australian tertiary cancer care centre.

To identify the number and timing of audiology encounters for adult oncology patients in a tertiary care setting in Australia. A retrospective case review was completed for 149 patients who received Cisplatin chemotherapy (CT) at a large, publicly funded tertiary hospital in Brisbane, Queensland, Australia between 1st January and 31st December 2019. Patient data was extracted from the Queensland Oncology Repository (QOR) provided by Cancer Alliance Queensland (CAQ). The number of audiology encounters was low overall with a median of 0 and interquartile range (IQR) of 0-1. Of the entire patient cohort, there was a mean of 1.2 encounters with 56% of patients not engaging with audiology. Where audiology did occur, encounters were most likely before or early in the CT treatment period. This study has demonstrated engagement with audiology services for patients undergoing CT treatment was limited with the few audiology engagements occurring before or early in the CT treatment period. Further research is needed to identify the barriers and facilitators to accessing audiological ototoxic monitoring (OtoM) during chemotherapy treatment in hospitals in Australia. Early identification of ototoxic hearing loss offers the opportunity to minimise further exposure to the ototoxic agent, minimise functional and communication impacts for the patient and provide early opportunity for discussion, education and counselling with patients, carers and their treating team. This, in turn, is expected to improve health related quality of life.

Boosting Antioxidant Defense: The Effect of Astaxantin on Superoxidase Dismutase and Malondialdehyde Reduction in Patients with Head and Neck Cancer Receiving Cisplatin Chemotherapy.

Background: Superoxide dismutase (SOD) can be decreased and malondialdehyde (MDA) can be increased in patients with head and neck cancer (HNC) as a result of reactive oxygen species (ROS) brought on by cisplatin. Astaxanthin is one of the external antioxidants required to combat ROS by raising SOD and lowering MDA. The purpose of this study is to demonstrate that astaxanthin can raise SOD and lower MDA in patients with HNC caused by cisplatin. Methods: 42 research subjects were randomly assigned to two groups in a double-blind, randomized controlled trial pre-post test design. Astaxanthin 4 mg BID was administered to the treatment group, whereas a single dosage of 500 mg of vitamin C and 250 mg of vitamin E IU was given to the control group. According to the Mann Whitney test, if p < 0.05, there is a significant difference in the delta of the decrease in SOD and MDA levels between the astaxanthin and vitamin C & E groups. Results: There were 42 research subjects, with a mean age of 48.2 years, a 2:1 male to female ratio, 23 (54.8%) with nasopharyngeal cancer, 32 (76.2%) with stage IV, 14 (33.3%) with cycle IV, 24 (57.1%) with paclitaxel-Cisplatin, 31 (73.8%) with Eastern Cooperative Oncological Group (ECOG) I, and 31 (73.8%) with Normal Body Mass Index. While there was a substantial drop in MDA (p=0.000), there was no significant difference in the delta reduction in SOD (p=0.443). Conclusion: Patients with HNC who receive cisplatin chemotherapy can have an increase in SOD and a decrease in MDA after receiving astaxanthin for 21 days.

Innovative infusion center assessments of chemotherapy-induced neurotoxicities: A pilot study supporting early and routine screenings as part of survivorship programs.

e24102 Background: More than 50% of patients treated with taxane and platinum chemotherapy experience neurotoxic adverse events due to treatment, including neuropathy, hearing loss or cognitive impairment. However, because risk factors and clinical trajectory of these toxicities remain poorly understood, it is not yet clear how or when patients should be screened. Innovative technology, such as tablet-based screening tools, create unique opportunities to capture patient symptoms, better understand potentially long-lasting side effects, and determine when to start either preventive or treatment/rehabilitation options. Methods: We assembled a multidisciplinary team from oncology, nursing, and audiology. IRB permission was obtained to perform a longitudinal observational pilot to assess the feasibility of performing chair-side neurotoxicity screenings in the infusion center of an urban safety net health system. Five infusion center nurses were recruited to collect data using a tablet-based application on 55 patients who met the inclusion criteria including chemotherapy-naive patients and fluent in English. Neuropathy and cognitive impairment were measured by validated standardized subjective scales (the Chemotherapy Induced Peripheral Neuropathy Assessment Tool, and the Attentional Function Index, respectively) and objective pure-tone audiometry (SHOEBOX Audiometry). Descriptive statistics were used to summarize outcome data. Results: Baseline assessments were completed on 48/55 patients with 37 completing at least one or up to 6 repeated assessments. All participants had baseline assessments before their first cycle by a chemo-certified RN in the infusion chair. Our sample included 55 adults aged 29 to 81 years, of whom 75% were females. 61% of participants were diagnosed with a gynecologic cancer, and 51% consented to receive Paclitaxel and Carboplatin chemotherapy regimen, 29% consented to receive Cisplatin chemotherapy, the remaining 20% consented to receive Oxaliplatin, Docetaxel, or Carboplatin alone. Significant changes occurred in all 3 symptoms by cycle 6 of chemotherapy with 45% of participants experiencing neuropathy, 13% experiencing a clinically significant change in hearing, and 30% experiencing self-reported cognitive concern by the 6th cycle. Ototoxicity and neurotoxicity scores followed the same trajectory of an increase or worsening in scores over time from cycle 1 to cycle 6. Conclusions: Use of innovative, portable tablet-based screening tool can be effectively used to capture symptoms of neuropathy chair-side as patients undergo chemotherapy. These observations support the need to better assess these approaches so that they can be used to optimize clinical outcomes and patient quality of life.

Fluoxetine, fluvoxamine, and hearing loss or tinnitus after cisplatin treatment: A retrospective cohort study.

Cisplatin use is often limited by its ototoxic side effects, which can lead to irreversible hearing loss. Preventing cisplatin-induced ototoxicity is crucial to improve patient outcomes. Fluoxetine and fluvoxamine, both selective serotonin reuptake inhibitors antidepressants, inhibit the NLR pyrin domain-containing protein 3 inflammasome, a potential therapeutic target for preventing ototoxicity. However, human studies have not evaluated if these antidepressants may protect against cisplatin-induced ototoxicity. The object of this study is to assess the association between fluoxetine or fluvoxamine use and incidence of hearing loss or tinnitus in a large cohort of patients receiving cisplatin chemotherapy. We use a retrospective cohort study within the U.S. Department of Veterans Affairs healthcare system. Adult patients with cancer who received cisplatin chemotherapy between 2000 and 2023 are included. Incidence of ototoxicity, defined by international classification of diseases revision 9-CM or international classification of diseases revision 10-CM diagnoses of hearing loss or tinnitus is compared between concurrent use of fluoxetine or fluvoxamine and cisplatin alone. A total of 20,552 patients were included. Of those, 489 received cisplatin and fluoxetine or fluvoxamine. After propensity score adjustment, the hazard of ototoxicity was lower in the group receiving fluoxetine or fluvoxamine compared to the group receiving cisplatin alone (HR = 0.62, 95% CI = (0.41-0.94)). Fluoxetine or fluvoxamine use may be associated with a reduced risk of cisplatin-induced ototoxicity. Randomized clinical trials are needed to confirm these findings and establish the efficacy of the medications in ototoxicity prevention. Further research is also warranted to investigate the potential mechanisms underlying this protective effect.

Erythrocyte PIG-A mutant frequencies in cancer patients receiving cisplatin.

Cisplatin is a primary chemotherapy choice for various solid tumors. DNA damage caused by cisplatin results in apoptosis of tumor cells. Cisplatin-induced DNA damage, however, may also result in mutations in normal cells and the initiation of secondary malignancies. In the current study, we have used the erythrocyte PIG-A assay to evaluate mutagenesis in non-tumor hematopoietic tissue of cancer patients receiving cisplatin chemotherapy. Twenty-one head and neck cancer patients undergoing treatment with cisplatin were monitored for the presence of PIG-A mutant total erythrocytes and the young erythrocytes, reticulocytes (RETs), in peripheral blood for up to five and a half months from the initiation of the anti-neoplastic chemotherapy. PIG-A mutant frequency (MF) in RETs increased at least two-fold in 15 patients at some point of the monitoring, while the frequency of total mutant RBCs increased at least two-fold in 6 patients. A general trend for an increase in the frequency of mutant RETs and total mutant RBCs was observed in 19 and 18 patients, respectively. Only in one patient did both RET and total RBC PIG-A MFs did not increase at any time-point over the monitoring period. Cisplatin chemotherapy induces moderate increases in the frequency of PIG-A mutant erythrocytes in head and neck cancer patients. Mutagenicity measured with the flow cytometric PIG-A assay may serve as a tool for predicting adverse outcomes of genotoxic antineoplastic therapy.

Effect of Astaxanthin Supplementation in Preventing Anemia in Head and Neck Cancer Patients Receiving Cisplatin Chemotherapy

The incidence of anemia due to reactive oxygen species (ROS) in patients with head and neck cancer (HNC) can be caused by a side effect of cisplatin chemotherapy, namely myelosuppression. In the presence of ROS, external antioxidants are needed, including astaxanthin as an antioxidant to neutralize and fight ROS in preventing anemia. This study aims to prove and analyze the antioxidant effect of astaxanthin in preventing anemia in HNC patients due to cisplatin chemotherapy for 3 weeks. The study design was a randomized controlled trial pre-post test design, involving 42 research subjects who were randomly divided into two groups, then 3 cc of blood was taken I to check the hemoglobin level and the number of erythrocytes. The treatment group was given astaxanthin 2x4 mg and the control group was given a combination of vitamin C 1x500 mg and vitamin E 1x250 IU for 3 weeks then 3 cc of blood was taken II to check hemoglobin levels and erythrocyte counts. The independent variable is intake of astaxanthin, the dependent variable is hemoglobin level and the number of erythrocytes and the confounding variables are age, sex, type of HNC, stage of HNC, ECOG and BMI. Data analysis was performed by the Descriptive test, Levene test, Shapiro Wilks, Wilcoxon test, and Mann-Whitney test. The significance of the hypothesis test was obtained with p&lt;0.05. The 42 research subjects met the inclusion criteria, most aged between 41-50 years, male and female ratio 2:1, The most HNC were Nasopharyngeal Cancer, the most HNC stage was stage IV, the most HNC performance status was ECOG I and the most HNC patients had normal BMI. There was a significant difference in hemoglobin levels p=0.012 (p&lt;0.05) and the number of erythrocytes, p=0.04 (p&lt;0.05) between the treatment and control groups. There was a significant difference in hemoglobin levels after therapy in the treatment and control groups p=0.012 (p&lt;0.05) and the number of erythrocytes p=0.04 (p&lt;0.05) between the treatment and control groups. Astaxanthin can prevent anemia in the form of decreased hemoglobin levels and the number of erythrocytes in HNC patients who receive cisplatin chemotherapy.Keywords: astaxanthin, anemia, HNC, cisplatin, ROS.

USP10 promotes migration and cisplatin resistance in esophageal squamous cell carcinoma cells.

Cisplatin-based chemotherapy is the main treatment option for advanced or metastatic esophageal squamous cell carcinoma (ESCC). However, most ESCC patients develop drug resistance within 2years after receiving cisplatin chemotherapy. Ubiquitin-specific protease 10 (USP10) is abnormally expressed in a variety of cancers, but the mechanistic roles of USP10 in ESCC are still obscure. Here, the effects of USP10 on the migration and cisplatin resistance of ESCC in vivo and in vitro and the underlying mechanisms have been investigated by bioinformatics analysis, RT-PCR, western blotting, immunoprecipitation, immunohistochemistry, cell migration and MTS cell proliferation assays, deubiquitination assay, and mouse tail vein injection model. USP10 was significantly up-regulated in ESCC tissues compared with adjacent normal tissues in both public databases and clinical samples and was closely associated with overall survival. Subsequent results revealed that USP10 contributed to the migration and cisplatin resistance of ESCC cells, while knocking down USP10 in cisplatin-resistant cells exhibited opposite effects in vitro and in vivo. Further Co-IP experiments showed that integrin β1 and YAP might be targets for USP10 deubiquitination. Moreover, deficiency of USP10 significantly inhibited the migrative and chemo-resistant abilities of ESCC cells, which could be majorly reversed by integrin β1 or YAP reconstitution. Altogether,USP10 was required for migration and cisplatin resistance in ESCC through deubiquinating and stabilizing integrin β1/YAP, highlighting that inhibition of USP10 may be a potential therapeutic strategy for ESCC.

A toddler with testosterone: where did it come from?

Precocious development of secondary sexual characters not involving pulsatile gonadotropin secretion is known as gonadotropin independent precocious puberty or peripheral precocious puberty (PPP). This form of sexual precocity in males can occur due to gonadal, adrenal, or other testosterone secreting tumors (teratomas, hepatomas, and choriocarcinomas), untreated congenital adrenal hyperplasia, testotoxicosis, and familial male limited precocious puberty. We report a case of a 2-year-old boy with PPP caused due to hepatoblastoma. Complete surgical resection of the tumor was done, and the child received cisplatin chemotherapy.

Levels of APE1 Repair Gene and CLEC4M in Lung Cancer Patients Receiving Cisplatin Chemotherapy.

This study aimed to detect the levels of apurinic/apyrimidinic endonuclease 1 (APE1) gene expression and C-type lectin domain family 4 member M (CLEC4M) and their association with cisplatin chemotherapy in lung cancer patients. Overall, 105 individuals who attended the Al-Amal National Hospital for Cancer Management, Baghdad, Iraq, were enrolled in the study and divided into three equal groups. The groups included the patients newly diagnosed with lung cancer, cancer patients who received cisplatin, and the healthy control group. All study groups were subjected to the sampling of the venous blood for molecular analysis by real-time polymerase chain reaction (RT-PCR) to detect the APE1 gene and enzyme-linked immunosorbent assay (ELISA) for serological testing to measure the concentration of CLEC4M protein. Significantly, the values of both cancer groups were higher than those reported in the control group. The relative index revealed a significant difference in the mean fold change level of APE1 in the newly diagnosed group (3 fold) and cisplatin therapy patients group (2 fold), compared to the control group (P=0.005). No significant differences were detected between the two cancer groups in terms of fold change mean of expression, demographic characteristics, and cancer histological type. Regarding human CLEC4M protein level, cases receiving cisplatin (139.2±25.9) and newly diagnosed patients (331.0±38.1) had a highly significant difference with the control group (100.3±47.5, P<0.001). There was no significant difference between the concentration level of CLEC4M and all parameters in demographic characteristics and cancer histological type. This was the first study to demonstrate that higher expression levels of new APE1, CLEC4M, and glutathione, especially after chemotherapy, are beneficial as diagnostic and prognostic markers for resistance to platinum chemotherapy in Iraqi lung cancer patients.

MP56-02 THE EFFECT OF TUMOR MUTATIONAL BURDEN, PDL1 EXPRESSION, AND SOMATIC GENE ALTERATIONS ON ADVANCED BLADDER CANCER RESPONSE TO CISPLATIN CHEMOTHERAPY

You have accessJournal of UrologyCME1 Apr 2023MP56-02 THE EFFECT OF TUMOR MUTATIONAL BURDEN, PDL1 EXPRESSION, AND SOMATIC GENE ALTERATIONS ON ADVANCED BLADDER CANCER RESPONSE TO CISPLATIN CHEMOTHERAPY John Heard, Eric Lo, Peris Castaneda, and Michael Ahdoot John HeardJohn Heard More articles by this author , Eric LoEric Lo More articles by this author , Peris CastanedaPeris Castaneda More articles by this author , and Michael AhdootMichael Ahdoot More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003309.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cisplatin based chemotherapy is a mainstay of treatment for patients with advanced bladder cancer, however not all patients achieve clinical response. We sought to understand how tumor mutational burden (TMB), PDL1 expression, and somatic tumor alterations were associated with response to cisplatin therapy by utilizing the Tempus Lens platform, a web-based library of clinical and molecular data. METHODS: We selected patients on the Lens platform, managed by Tempus (Chicago, Illinois), with stage 3 and 4 bladder cancer who received cisplatin chemotherapy. Somatic gene mutations via next-generation sequencing (NGS), TMB (>10 mutations/Mb), and PDL1 expression on tumor and immune cells were assessed against rates of clinical response. Analyses were performed with chi-square test at significance of p=0.05. RESULTS: 5.4 million patients were assessed as part of the Lens platform. 4,049 patients with stage 3 or 4 bladder cancer were identified. Clinical response to cisplatin therapy and NGS data was available for 305. In this dataset, PDL1 expression on greater than 10% of tumor cells was associated with worse response to cisplatin therapy as 23% of patients with progressive disease (PD) had this finding compared to 6% of those with complete response (CR) (p=0.046) (Table 1). Similarly, PDL1 expression on great than 10% of tumor infiltrating immune cells was lower in patients with CR compared to PR (0% vs 29%, p=0.02). TMB appeared to be associated with improved response, with high TMP seen in 27% of patients with CR and 19% in patients with PD, although this difference was not significant (p=0.14). Certain somatic alterations were associated with CR while others were associated with PD (Figure 1). CONCLUSIONS: While it is known that PDL1 expression is important in response to immunotherapy, our data suggest PDL1 expression by tumor and immune cells is also associated with response to cisplatin chemotherapy. Specific somatic alterations may be associated with response or lack of response to cisplatin as well. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e773 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information John Heard More articles by this author Eric Lo More articles by this author Peris Castaneda More articles by this author Michael Ahdoot More articles by this author Expand All Advertisement PDF downloadLoading ...

MP12-08 EVALUATING THE IMPACT OF EXCLUDING THE RACE FACTOR FROM THE eGFR EQUATION ON BLADDER CANCER TREATMENT OPTIONS

You have accessJournal of UrologyCME1 Apr 2023MP12-08 EVALUATING THE IMPACT OF EXCLUDING THE RACE FACTOR FROM THE eGFR EQUATION ON BLADDER CANCER TREATMENT OPTIONS Amir Khan, Shu Wang, Rehan Choudhary, Michael Phelan, Eberechukwu Onukwugha, and M. Minhaj Siddiqui Amir KhanAmir Khan More articles by this author , Shu WangShu Wang More articles by this author , Rehan ChoudharyRehan Choudhary More articles by this author , Michael PhelanMichael Phelan More articles by this author , Eberechukwu OnukwughaEberechukwu Onukwugha More articles by this author , and M. Minhaj SiddiquiM. Minhaj Siddiqui More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003227.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The estimated glomerular filtration rate (eGFR) equation is based on several factors among which the race factor has been broadly criticized. In September 2021, the National Kidney Foundation and American Society of Nephrology Task Force announced a new race-free calculation for eGFR. Aspects of treatment decisions for muscle-invasive bladder cancer (MIBC) are dependent on eGFR, specifically neoadjuvant cisplatin eligibility and choice of diversion with cystectomy. Herein, we evaluate the impact of removal of race-based eGFR calculation on the management of patients with MIBC. METHODS: Using the National Surgical Quality Improvement Program database, adult patients diagnosed with MIBC and who received radical cystectomy from 2015 to 2020 were included in this study. eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) equation. We calculated the proportion of African American patients who were candidates for neobladder urinary diversions and cisplatin-based chemotherapy using >30 and >60 ml/min/1.73m2 as the cutoff for eGFR, respectively, as calculated with and without the race factor. RESULTS: African Americans constituted 4.5% (579) of the total sample population (12,192) among which 39.7% (230) were female and 60.3% (349) were male. There was no association of eGFR with gender. Using the MDRD equation, the mean eGFR decreased from 70.0 to 57.8 ml/min/1.73m2 after removing the race factor. With the adjusted eGFR without race, 4.1% fewer patients (94.6% vs 90.5%) were eligible for neobladder urinary diversion with a >30 ml/min/1.73m2 eGFR cutoff. Furthermore, among patients who were previously eligible to receive cisplatin chemotherapy, 18.0% fewer patients (63.0% vs 45.0%) would remain eligible with a >60 ml/min/1.73m2 eGFR. (Figure 1) CONCLUSIONS: Excluding race from the eGFR equation will preclude some previously eligible African American patients for certain treatment in bladder cancer management. Further studies are needed to understand the relative risks and benefits of decisions that are based on the adjusted eGFR. Source of Funding: No source of funding © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e136 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amir Khan More articles by this author Shu Wang More articles by this author Rehan Choudhary More articles by this author Michael Phelan More articles by this author Eberechukwu Onukwugha More articles by this author M. Minhaj Siddiqui More articles by this author Expand All Advertisement PDF downloadLoading ...

The STAT1/HMGB1/NF-κB pathway in chronic inflammation and kidney injury after cisplatin exposure.

Rationale: Cisplatin, a potent chemotherapeutic drug, induces side effects in normal tissues including the kidney. To reduce the side effects, repeated low-dose cisplatin (RLDC) is commonly used in clinical setting. While RLDC reduces acute nephrotoxicity to certain extents, a significant portion of patients later develop chronic kidney problems, underscoring the need for novel therapeutics to alleviate the long-term sequelae of RLDC therapy. Methods: In vivo, the role of HMGB1 was examined by testing HMGB1 neutralizing antibodies in RLDC mice. In vitro, the effects of HMGB1 knockdown on RLDC-induced nuclear factor-κB (NF-κB) activation and fibrotic phenotype changes were tested in proximal tubular cells. To study signal transducer and activator of transcription 1 (STAT1), siRNA knockdown and its pharmacological inhibitor Fludarabine were used. We also searched the Gene Expression Omnibus (GEO) database for transcriptional expression profiles and evaluated kidney biopsy samples from CKD patients to verify the STAT1/HMGB1/NF-κB signaling axis. Results: We found that RLDC induced kidney tubule damage, interstitial inflammation, and fibrosis in mice, accompanied by up-regulation of HMGB1. Blockage of HMGB1with neutralizing antibodies and Glycyrrhizin suppressed NF-κB activation and associated production of pro-inflammatory cytokines, reduced tubular injury and renal fibrosis, and improved renal function after RLDC treatment. Consistently, knockdown of HMGB1 decreased NF-κB activation and prevented the fibrotic phenotype in RLDC-treated renal tubular cells. At the upstream, knockdown of STAT1 suppressed HMGB1 transcription and cytoplasmic accumulation in renal tubular cells, suggesting a critical role of STAT1 in HMGB1 activation. Upregulation of STAT1/HMGB1/NF-κB along with inflammatory cytokines was also verified in kidney tissues of CKD patients. Conclusion: These results unravel the STAT1/HMGB1/NF-κB pathway that contributes to persistent inflammation and chronic kidney problems after cisplatin nephrotoxicity, suggesting new therapeutic targets for kidney protection in cancer patients receiving cisplatin chemotherapy.

A Comparison of the Efficacy of 5 mg Olanzapine and Aprepitant in the Prevention of Multiple-Day Cisplatin Chemotherapy-Induced Nausea and Vomiting

Objective The significance of this article is to talk about aprepitant and olanzapine 5 mg, compare them, and deeply explore the safety or effectiveness during the whole process of multiple-day cisplatin chemotherapy-induced vomiting and nausea. Methods This trial was randomized and prospective. It is needed to receive cisplatin chemotherapy (25 mg/m2/d) for three days. Its patients would need to choose to use 5 mg olanzapine or aprepitant for this treatment, combined with 5-HT3 receptor antagonist plus dexamethasone. The primary endpoints were the total protection (TP) during the acute phase (AP) (0–24 hours), delayed phase (DP) (25–120 hours), and overall phase (OP) (0–120 h) between the two groups. The secondary endpoints were the complete response (CR) and total control (TC) during the three phases. The first time of the whole process is particularly important and needs to be observed vigorously. However, the time of the patient's first vomiting symptom is also compared accurately by using the Kaplan–Meier curve. The functional life index vomiting (FLIE) was used to calculate and carefully evaluate the serious impact of nausea and vomiting (CINV) induced by the whole chemotherapy process on the quality of life. About olanzapine, its related symptoms and other side effects and aprepitant were also recorded. Results (1) The primary endpoint TP rates of the olanzapine and aprepitant groups were similar; for the AP, they were 94.23% (98/104) vs. 95.45% (98/106) P=0.61(P=0.61); for the DP, they were 54.81% (57/104) vs. 54.72% (58/106) (P=0.99), and for the OP, the values were 53.79% (58/105) and 55.31% (56/104), respectively (P=0.99). The secondary endpoints, the TC rates, and CR rates were also comparable in the three phases (P > 0.05). (2) After research and display, the results showed that there was no significant difference between the two groups when they were used for the first time of vomiting and the FLIE index (P > 0.05). (3) The main olanzapine-related adverse event was drowsiness, while that of aprepitant was constipation. Conclusion The efficacy of 5 mg olanzapine was similar to that of aprepitant, and it also showed an advantageous economic potency ratio in preventing CINV induced by multiple-day cisplatin chemotherapy with increased sedation side effects.

O2-2 The effect of mannitol versus intravenous diuretics in preventing cisplatin-induced nephrotoxicity: A meta-analysis

Cisplatin is one of the most widely used chemotherapeutic agents in the treatment of a majority of malignancies. However, it is associated with nephrotoxicity despite adequate hydration prior to cisplatin administration. We aimed to determine the efficacy and safety of diuretics versus mannitol in preventing cisplatin-induced nephrotoxicity among adult patients with cancer receiving cisplatin chemotherapy.

Carbon Ion Beam Boost Irradiation in Malignant Tumors of the Nasal Vestibule and the Anterior Nasal Cavity as an Organ-Preserving Therapy.

BackgroundSurgery and radiotherapy are current therapeutic options for malignant tumors involving the nasal vestibule. Depending on the location, organ-preserving resection is not always possible, even for small tumors. Definitive radiotherapy is an alternative as an organ-preserving procedure. Carbon ion beam radiotherapy offers highly conformal dose distributions and more complex biological radiation effects eventually resulting in optimized normal tissue sparing and improved outcome. The aim of the current study was to analyze toxicity, local control (LC), and organ preserving survival (OPS) after irradiation of carcinoma of the nasal vestibule with raster-scanned carbon ion radiotherapy boost (CIRT-B) combined with volumetric intensity modulated arc therapy (VMAT) with photons.MethodsBetween 12/2015 and 05/2021, 21 patients with malignant tumors involving the nasal vestibule were irradiated with CIRT-B combined with VMAT and retrospectively analyzed. Diagnosis was based on histologic findings. A total of 17 patients had squamous cell carcinoma (SCC) and 4 had other histologies. In this series, 10%, 67%, and 24% of patients had Wang stages 1, 2, and 3 tumors, respectively. Three patients had pathologic cervical nodes on MRI. The median CIRT-B dose was 24 Gy(RBE), while the median VMAT dose was 50 Gy. All patients with pathologic cervical nodes received simultaneously integrated boost with photons (SIB) up to a median dose of 62.5 Gy to the pathological lymph nodes. Eight patients received cisplatin chemotherapy. All patients received regular follow-up imaging after irradiation. Kaplan–Meier estimation was used for statistical assessment.ResultsThe median follow-up after irradiation was 18.9 months. There were no common toxicity criteria grade 5 or 4 adverse events. A total of 20 patients showed grade 3 adverse events mainly on skin and mucosa. All patients were alive at the end of follow-up. The median OPS after treatment was 56.5 months. The 6- and 24-month OPS were 100% and 83.3%, respectively. All local recurrences occurred within 12 months after radiotherapy. The median progression free survival (PFS) after treatment was 52.4 months. The 6-, 12-, and 24-month PFS rates were 95%, 83.6%, and 74.3%, respectively.ConclusionCIRT-B combined with VMAT in malignant tumors of the nasal vestibule is safe and feasible, results in high local control rates, and thus is a good option as organ-preserving therapy. No radiation-associated grade 4 or 5 acute or late AE was documented.

Hyponatremia timing, incidence, and associated risk factors in patients treated with cisplatin for lung cancer: a retrospective study.

The incidence of cisplatin-derived hyponatremia remains unknown, although nausea, vomiting, and renal dysfunction are common adverse events of cisplatin, a platinum-based preparation. The factor contributing to hyponatremia is described but not well known. This study aimed to retrospectively investigate the incidence of hyponatremia, timing, and associated risk factors. This study surveyed patients with lung cancer who received cisplatin chemotherapy from August 2013 to July 2019 at Shizuoka Cancer Center. The severity of hyponatremia was evaluated based on Common Terminology Criteria for Adverse Events. A total of 814 patients were included in this study. 682 (83.7%) patients had hyponatremia of any grade: grade 1 (<135-130 mmol/L), grade 3 (<130-120 mmol/L), and grade 4 (<120 mmol/L) hyponatremia were observed in 619 (76.0%), 51 (6.3%), and 12 (1.5%) patients, respectively. Of 63 patients with grade 3-4 hyponatremia, 43 (68.3%) developed it in the first treatment cycle. In multivariate analysis, the short hydration regimen (<3000 mL/day) has a lower incidence of grade 3-4 hyponatremia than a normal (>3000 mL) hydration regimen (OR: 0.35 [0.16-0.80], p = 0.013). In addition, if the Na+ value before the start of administration is < 135mmol/L, the incidence of grade3 and 4 hyponatremia is higher (OR:0.14 [0.07-0.28], p < 0.001). Hyponatremia due to cisplatin is likely to occur in patients with low Na levels before administration, such as the elderly. Since short hydration might avoid diuretics, hydration methods might need to be reconsidered to prevent hyponatremia.

Https://theijmed.com/index.php?journal=theijmed&amp;page=issue&amp;op=view&amp;path%5B%5D=24

Background: Nasopharyngeal cancer (NPC) is a malignant tumor located in the nasopharynx, which can be treated by Cisplatin, a chemotherapy that has a side effect of increasing the production of Reactive Oxygen Species (ROS) that can damage the liver. We aim to determine the effect of giving Mahkota Dewa ( Phaleria macrocarpa ) as an antioxidant on liver function of NPC patients receiving Cisplatin chemotherapy. Subjects and Method: Forty subjects of stage III and IV Nasopharyngeal Carcinoma patients were divided into treatment and control groups. Subjects will be tested for SGOT SGPT before cisplatin chemotherapy. The treatment group was given Phaleria macrocarpa capsules 300 mg/24 hours for 5 weeks since a week before chemotherapy. The control group was given placebo capsules/24 hours for 5 weeks since a week before chemotherapy. The patients received two series of cisplatin chemotherapy with an interval of 3 weeks, then a second blood sample was taken 1 week after the second series of cisplatin chemotherapy. Results: There was a significant difference in SGOT levels in the post-treatment group of Phaleria macrocarpa and control, as well as the difference in the pre- and post- treatment group between the Phaleria macrocarpa and control groups. Also, there was a significant difference in SGPT levels in the pre- and post- treatment in the Phaleria macrocarpa and control groups. Conclusion: The administration of Phaleria macrocarpa has an effect on decreasing the levels of SGOT and SGPT in NPC patients receiving Cisplatin chemotherapy therapy Keywords: Phaleria macrocarpa , SGOT, SGPT, Nasopharyngeal Carcinoma, Cisplatin Correspondence: Adi Januar Akbar. ENT Department of Diponegoro University. Prof. Sudarto Street No. 13, Tembalang, Tembalang Sub-district, Semarang City, Central Java, 50275. Email: diaz17akbarsaleh­@gmail.com. +628161455179. Indonesian Journal of Medicine (2022), 07(01): 1-8 https://doi.org/10.26911/theijmed.2022.07.01.01

Pathogenic TP53 mutations influence chemotherapy response and survival rate of HPV-negative oral carcinomas

Background/Aim. Oral squamous cell carcinoma (OSCC) is the most common tumor type of head and neck carcinomas, characterized by a high recurrence rate and patients? poor survival. Further elucidation of the function and regulation of the TP53, a pivotal tumor suppressor gene, would provide advances in predicting the clinical behavior, prognosis, and chemotherapy response of OSCC patients. Thus, we investigated the association of TP53 gene mutations with survival and response to cisplatin chemotherapy in human papilloma virus (HPV)-negative OSCC patients. Methods. The potential clinical relevance of TP53 mutations was analyzed in 82 patients with HPV-negative OSCC. All patients underwent radiotherapy, and 25 patients received cisplatin chemotherapy. A negative HPV status was deter-mined by type-specific polymerase chain reaction (PCR) for high-risk HPV 16, 18, 31, and 33. Targeted sequencing of TP53 exons 4?8 was assessed by Sanger sequencing. Results. Of 82 HPV-negative OSCC patients, 49 (59.79%) had TP53 mutations, and 26 patients (31.7%) carried pathogenic TP53 mutations. Patients with pathogenic TP53 mutations had significantly reduced overall survival (p = 0.009). Recurrence status, but not TP53 mutations, was an independent marker of poor survival in our cohort [hazard ratio (HR) = 4.733, 95% confidence interval (95% CI): 2.027?11.053, p = 0.0001]. In the sub-cohort of patients who underwent cisplatin-based chemotherapy, pathogenic TP53 mutations were predictors of poor response to chemotherapy (p = 0.026). Conclusion. Our findings indicate that pathogenic TP53 mutations in HPV-negative OSCC tumors could be a prognostic marker of patients? reduced overall survival. In addition, pathogenic TP53 mutations in HPV-negative OSCC could be a marker of poor chemotherapy response of OSCC patients.

The effect of combined TPF and intensity modulated radiotherapy after TPF induction chemotherapy on locally advanced nasopharyngeal carcinoma: a retrospective analysis.

To evaluate the efficacy and toxicity of docetaxel, cisplatin, and fluorouracil (TPF) regimen followed by intensity modulated radiotherapy (IMRT) on locally advanced nasopharyngeal carcinoma (NPC). A total of 150 patients with locally advanced NPC [American Joint Committee on Cancer (AJCC) 2009 stage IIIa-IVb] received 2 or 3 cycles of a TPF regimen as induction chemotherapy. A group of 67 participants (TPF group) continued to receive TPF chemotherapy and radiotherapy, and the remaining 83 participants (P group) received cisplatin chemotherapy and radiotherapy. A median follow-up of 35 months (4-66 months) showed that there was no significant difference between P group and TPF group in progression-free survival (PFS) and overall survival (OS). The incidence rate of myelosuppression at 3-4 degrees was 16.9% and 34.3% in the P group and TPF group (P=0.029), respectively, and the oral mucosa reaction at 3-4 degrees was 18.1% and 37.3% in the P group and TPF group, respectively (P=0.007). The 3-4-degree skin reaction in the P group and TPF group was 15.7% and 29.9% (P=0.030), respectively. The rate of liver function injury in the P group was significantly lower than that in TPF group (P<0.05). Compared with concurrent cisplatin chemotherapy and radiotherapy, the concurrent TPF regimen and IMRT showed no significant improvement in OS and PFS in patients with advanced NPC, but exhibited more severe hematologic toxicity, oral mucosal responses, skin reactions, and liver functional impairment.

Effect of Mannitol Hydration as Renoprotective on Cisplatin Induced Nephrotoxicity (CIN) in Head and Neck Cancer Patients

Background: Cisplatin is a cytostatic agent used as treatments in head and neck cancer patients.Nephrotoxicity is one of cisplatin major side effects. This study aimed to evaluate the renoprotectiveeffect of mannitol-hydration administration in head and neck cancer patients who receive cisplatinchemotherapy. Methods: This was a cohort observational study to analyze the renal function of head andneck cancer patients who receives cisplatin before and after mannitol-hydration administration in IRNASurgery and Soekardja Room of Chemotherapy at RSUD Dr. Soetomo Surabaya during June – September2018. The data obtained were BUN, SCr, and eClCr Cockroft-Gault of each cycle. Result: A total of 52patients were evaluated. The average value of creatinine serum, creatinine clearance, and BUN at each cyclewere fluctuate. However, the average value of creatinine serum and BUN were within the normal limit.The result of statistical analysis using paired t-test in those parameters at each cycle were not statisticallysignificant (p &gt; 0,05) after mannitol administration except during first cycle to second cycle the SCr increasedsignificantly and eClCr was decreased significantly (p-value 0,024; 0,006, CI 95% respectively ). At fourthcycle the eClCr also decreased significantly (p value 0,008, CI 95%). Conclusion: The renoprotective effectof mannitol in head and neck cancer patients who receive cisplatin chemotherapy is sufficiently adequatewhich can maintain the value of BUN and creatinine serum of patients at each cycle within the normal limit.