The assessment of the mechanism of action of lauric acid in the context of oral cancer through integrative approach combining network pharmacology and molecular docking technology.

OBJECTIVES: Lauric acid has been investigated for its effects on various human cancer cell types, although limited research has been dedicated to its impact on oral cancer. In light of this, the objective of our study was to comprehensively assess the anticancer properties of lauric acid specifically in the context of oral cancer. This evaluation was achieved through an in-silico approach, leveraging network analysis techniques. By employing this methodology, we aimed to gain valuable insights into the potential therapeutic benefits of lauric acid for treating oral cancer. METHODS: The in-silico analysis involved determination of drug-likeness prediction, prediction of common targets between oral cancer and LA, protein-protein interactions (PPI), hub genes, top 10 associated pathways by gene ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway, molecular docking experiments. RESULTS: Our study pinpointed 23 common genes involved in critical cellular processes, including proliferation, apoptosis regulation, PI3K AKT cascade, and cell cycle control. Among them, CXCL8, MMP9, PPARA, MAPK1, and AR stood out in the top 10 pathways, particularly in the PI3K/AKT signaling pathway. This highlights the potential role of lauric acid in oral cancer treatment through the PI3K/AKT pathway and calls for further exploration of this mechanism. CONCLUSIONS: Our study highlights lauric acid's promising anticancer properties through computational analysis, offering a foundation for future research in cancer treatment development. This approach combines molecular insights with in-silico methods, paving the way for identifying therapeutic compounds and understanding their mechanisms. Lauric acid holds potential as a chemotherapeutic agent, opening up new avenues for cancer therapy exploration.

Assessment of neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil in patients with oral cavity cancer.

BACKGROUND: Chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) has been studied in patients with head and neck cancer. Its impact on patients with oral cavity cancer was not specified. METHODS: We consecutively reviewed medical files of patients with untreated oral cavity cancer who received neoadjuvant TPF chemotherapy in our department from January 2017 to April 2020. Outcomes included the objective response to TPF chemotherapy, factors associated with the response, and progression and survival in different response groups. RESULTS: A total of 167 patients were included, with half of stage IV disease. Complete or partial response was observed in 51 patients. A total of 91 patients had stable disease, and 25 patients had progressive disease. The response was not associated with age, sex, anatomic subsite, and the tumor's T stage. It was related with N stage (p < 0.001) and clinical stage (p = 0.004). Most patients with bulky nodes or nodes with obvious necrosis showed low response or even progressed after neoadjuvant TPF chemotherapy. The planned surgery was conducted in 159 patients. Disease relapse mostly occurred in 2 years after treatment. The 2-year overall survival and the progression-free survival were 89.0% and 85.2% for patients with complete or partial response, 62.4% and 55.6% for patients with stable disease, and 12.5% and 4.2% for patients with progressive disease, respectively. CONCLUSIONS: The response of neoadjuvant TPF chemotherapy in patients with oral cavity cancer is related to disease stage, especially the nodal stage. Patients with complete or partial response developed less progression events and better survival.

Clinical evaluation of a mobile, low-cost system for fluorescence guided photodynamic therapy of early oral cancer in India.

BACKGROUND: Morbidity and mortality due to oral cancer in India are exacerbated by a lack of access to effective treatments amongst medically underserved populations. We developed a user-friendly low-cost, portable fibre-coupled LED system for photodynamic therapy (PDT) of early oral lesions, using a smartphone fluorescence imaging device for treatment guidance, and 3D printed fibreoptic attachments for ergonomic intraoral light delivery. METHODS: 30 patients with T1N0M0 buccal mucosal cancer were recruited from the JN Medical College clinics, Aligarh, and rural screening camps. Tumour limits were defined by external ultrasound (US), white light photos and increased tumour fluorescence after oral administration of the photosensitising agent ALA (60 mg/kg, divided doses), monitored by a smartphone fluorescence imaging device. 100 J/cm2 LED light (635 nm peak) was delivered followed by repeat fluorescence to assess photobleaching. US and biopsy were repeated after 7-17 days. This trial is registered with ClinicalTrials.gov, NCT03638622, and the study has been completed. FINDINGS: There were no significant complications or discomfort. No sedation was required. No residual disease was detected in 22 out of 30 patients who completed the study (26 of 34 lesions, 76% complete tumour response, 50 weeks median follow-up) with up to 7.2 mm depth of necrosis. Treatment failures were attributed to large tumour size and/or inadequate light delivery (documented by limited photobleaching). Moderately differentiated lesions were more responsive than well-differentiated cancers. INTERPRETATION: This simple and low-cost adaptation of fluorescenceguided PDT is effective for treatment of early-stage malignant oral lesions and may have implications in global health.

The Oncology Care Model and Adherence to Oral Cancer Drugs: A Difference-in-Differences Analysis.

BACKGROUND: Adherence to oral cancer drugs is suboptimal. The Oncology Care Model (OCM) offers oncology practices financial incentives to improve the value of cancer care. We assessed the impact of OCM on adherence to oral cancer therapy for chronic myelogenous leukemia (CML), prostate cancer, and breast cancer. METHODS: Using 2014-2019 Medicare data, we studied chemotherapy episodes for Medicare fee-for-service beneficiaries prescribed tyrosine kinase inhibitors (TKIs) for CML, antiandrogens (ie, enzalutamide, abiraterone) for prostate cancer, or hormonal therapies for breast cancer in OCM-participating and propensity-matched comparison practices. We measured adherence as the proportion of days covered and used difference-in-difference (DID) models to detect changes in adherence over time, adjusting for patient, practice, and market-level characteristics. RESULTS: There was no overall impact of OCM on improved adherence to TKIs for CML (DID = -0.3%, 90% confidence interval [CI] = -1.2% to 0.6%), antiandrogens for prostate cancer (DID = 0.4%, 90% CI = -0.3% to 1.2%), or hormonal therapy for breast cancer (DID = 0.0%, 90% CI = -0.2% to 0.2%). Among episodes for Black beneficiaries in OCM practices, for whom adherence was lower than for White beneficiaries at baseline, we observed small improvements in adherence to high cost TKIs (DID = 3.0%, 90% CI = 0.2% to 5.8%) and antiandrogens (DID = 2.2%, 90% CI = 0.2% to 4.3%). CONCLUSIONS: OCM did not impact adherence to oral cancer therapies for Medicare beneficiaries with CML, prostate cancer, or breast cancer overall but modestly improved adherence to high-cost TKIs and antiandrogens for Black beneficiaries, who had somewhat lower adherence than White beneficiaries at baseline. Patient navigation and financial counseling are potential mechanisms for improvement among Black beneficiaries.

The effects of oral anticancer parity laws on out-of-pocket spending and adherence among commercially insured patients with chronic myeloid leukemia.

BACKGROUND: Over the past 12 years, 43 states and Washington DC have implemented oral anticancer medication parity laws in response to the burden of pharmacy cost sharing. Parity laws are designed to provide equal coverage and cost sharing between orally and parenterally administered anticancer medications for patients in commercial, fully insured health plans (FIHPs). However, there is considerable state-level variation in the requirements to achieve compliance with parity laws, and the clinical and economic effectiveness of parity is not fully known. OBJECTIVES: To (a) understand the impact of parity laws on out-of-pocket (OOP) spending and adherence to tyrosine kinase inhibitors (TKI) among commercially insured patients with chronic myeloid leukemia (CML) and (b) compare these effects across states with and without per prescription or per 30-day OOP spending limits as part of their parity laws. METHODS: Patients aged 18-64 years with CML, at least 1 pharmacy claim for a TKI, and residence in a state that implemented oral anticancer parity legislation between January 1, 2007, and January 1, 2017, were identified from the IBM MarketScan Commercial Claims and Encounters database. A propensity score-weighted difference-in-difference approach was used to measure the impact of parity on OOP spending and adherence in the 6 months after the first pharmacy claim for a TKI (index date) for patients enrolled in FIHPs (subject to parity) and self-funded health plans (SFHPs; exempt from parity). OOP spending was standardized to a 30-day equivalent amount and adjusted to 2017 US dollars. Adherence was assessed using the proportion of days covered (PDC), and patients were categorized as adherent with PDC ≥ 0.80. RESULTS: Of 1,887 patients initiating a TKI before or after their state's parity law, 678 (35.9%) were enrolled in FIHPs (480 before vs 198 after parity), and 1,209 (64.1%) were enrolled in SFHPs (688 before vs 521 after parity). Implementation of parity laws was not associated with any changes in mean OOP spending; however, it was associated with a reduced likelihood of paying $0 per 30 days across all states (adjusted difference-in-difference [aDD] OR = 0.662; 95% CI = 0.535-0.820) and states without OOP spending limits (aDD OR = 0.654; 95% CI = 0.508-0.848), but not in states with limits. Nonsignificant but directionally opposite changes at each end of the OOP spending distribution were observed for states with and without OOP spending limits, with increased spending observed at the 75th, 90th, and 95th percentiles in states without limits. Mean PDC and adherence showed a nonsignificant increase among FIHP and SFHP patients across all states, states with limits, and states without limits. CONCLUSIONS: Oral anticancer parity laws are not associated with reduced OOP spending or improved adherence in a commercially insured sample of patients with CML. These findings were consistent for states that included OOP spending limits as a component of their parity laws. DISCLOSURES: This study did not receive any external funding. Spargo, Yost, Raju, and Schroader are or were employees of Xcenda, which receives contracts from various industry partners unrelated to this work. There are no other conflicts of interest to disclose.

Outpatient oral anticancer agent utilization and costs in Manitoba from 2003 to 2016: a population-based study.

INTERVENTION: In April 2012, the Manitoba Home Cancer Drug Program (HCDP) was introduced to allow 100% coverage for eligible oral anticancer agents (OAA) and supportive medications for Manitobans with cancer requiring these therapies. RESEARCH QUESTIONS: What is the extent of use and cost of OAAs among outpatients in Manitoba from 2003/04 to 2015/16? Did the HCDP change OAA user and prescription patterns? METHODS: This was a retrospective, population-based study using administrative data to measure the prevalence of drug utilization over time and the impact of HCDP on OAA use and prescriptions using generalized linear models. Manitobans with cancer who filled an OAA or supportive medication covered by HCDP from 2003/04 to 2015/16 were included. RESULTS: This study included 22,393 people with cancer who filled an OAA prescription. The prevalence of OAA use increased from 222 per 100,000 to 328 per 100,000 from 2003/04 to 2015/16. Hormone therapy for breast cancer was the most common class of OAA used (increased from 154 per 100,000 to 231 per 100,000). We observed a 2.6-fold decrease in the prevalence of oral alkylating agents and a 10.7-fold increase in the prevalence of protein kinase inhibitors during the study period. The total cost of targeted OAAs per year for all Manitobans with cancer increased from $1.8 million to $19 million. CONCLUSION: We observed an increase in OAA prevalence and the cost of oral targeted chemotherapy is high. Our findings underline the need for addressing these high-cost medications in future developments of a national drug program.

RéSUMé: INTERVENTION: Le Manitoba a introduit en avril 2012 le Programme de médicaments anticancéreux pris à domicile (HCDP en anglais), qui offre un accès entièrement gratuit aux agents anticancéreux oraux (AAO) admissibles et aux médicaments d'appoint aux Manitobains atteints de cancer qui ont besoin de ces traitements. QUESTIONS DE RECHERCHE: Quelle a été l'utilisation des AAO par les malades externes au Manitoba entre 2003-2004 et 2015-2016 et quel en a été le coût? Le programme HCDP a-t-il changé les modes d'utilisation et de prescription des AAO? MéTHODE: Cette étude populationnelle rétrospective a utilisé des données administratives pour mesurer la prévalence de l'utilisation des médicaments au fil du temps et l'incidence du programme HCDP sur l'utilisation et la prescription des AAO à l'aide de modèles linéaires généralisés. Les Manitobains atteints de cancer qui ont fait exécuter une ordonnance pour un AAO ou un médicament d'appoint couvert par le programme HCDP entre 2003-2004 et 2015-2016 ont été inclus. RéSULTATS: L'étude a inclus 22 393 personnes atteintes de cancer ayant fait exécuter une ordonnance d'AAO. La prévalence de l'utilisation des AAO a augmenté, passant de 222 pour 100 000 à 328 pour 100 000 entre 2003-2004 et 2015-2016. L'hormonothérapie pour le cancer du sein a représenté la classe d'AAO la plus communément utilisée (en hausse de 154 pour 100 000 à 231 pour 100 000). Nous avons observé une diminution par un facteur de 2,6 de la prévalence des agents alcoylants oraux et une augmentation par un facteur de 10,7 de la prévalence des inhibiteurs de protéine kinase au cours de la période de l'étude. Le coût total annuel des AAO ciblés pour tous les Manitobains atteints de cancer est passé de 1,8 millions de dollars à 19 millions de dollars. CONCLUSION: Nous avons observé une augmentation de la prévalence des AAO, et le coût des agents chimiothérapeutiques oraux ciblés est élevé. Nos constatations confirment la nécessité d'aborder ces médicaments coûteux dans les versions futures d'un programme de médicaments national.

Oral alterations and oral health-related quality of life assessment in patients undergoing chemotherapy at a tertiary care center.

AIMS: This study was designed to assess the oral alterations and oral health related quality of life (OHRQoL) in patients undergoing chemotherapy for malignancies other than oral cancer. METHODS AND RESULTS: Oral alterations were studied by careful clinical examination prior to and at the end of three cycles of chemotherapy in 100 patients. OHRQoL was assessed by oral health impact profile (OHIP)-14 questionnaire. Fifty-four patients developed oral complications among which oral mucositis and pigmentation were the most commonly observed. OHRQoL was hampered in all patients as indicated by higher postchemotherapy scores as compared to prechemotherapy scores (P < .0001). Postchemotherapy scores were higher for patients who developed visible oral changes as compared to those who did not (P = .001). There was a weak positive correlation between the number of oral alterations and postchemotherapy scores for OHRQoL. CONCLUSIONS: Our study emphasizes the role of oral physicians in the healthcare team delivering chemotherapeutic treatment as regular oral examination, and timely symptomatic treatment is important for the overall well-being of the patient.

Nutritional assessment and prognosis of oral cancer patients: a large-scale prospective study.

BACKGROUND: To evaluate and compare the prognostic performance of four nutritional indicators body mass index (BMI), serum albumin (ALB), prognostic nutritional index (PNI) and nutritional risk index (NRI) in oral cancer patients, and to predict the response to chemotherapy in patients with different nutritional status. METHODS: This prospective study which involved 1395 oral cancer patients was conducted in Fujian, China from September 2007 to November 2018. The BMI, PNI and NRI were calculated according to the following formulas: BMI = weight / height2 (kg/m2), PNI = albumin (g/l) + 0.005 × lymphocyte (count/µl) and NRI = (1.519 × albumin, g/l) + (41.7× present/ideal body weight), respectively. The univariate and multivariate Cox proportional hazards models were used to compare the prognostic value of BMI, ALB, PNI and NRI in overall survival (OS) in oral cancer. RESULTS: Patients with BMI < 18.5 kg/m2 (VS 18.5 kg/m2 ≤ BMI < 24 kg/m2) had a poor survival outcome (HR = 1.585; 95% CI: 1.207-2.082 ). ALB, PNI, NRI were inversely correlated with OS of oral cancer (HR = 0.716; 95% CI: 0.575-0.891; HR = 0.793; 95% CI: 0.633-0.992; HR = 0.588; 95% CI: 0.469-0.738, respectively). In addition, the prognostic predictive performance of NRI was superior to BMI or ALB or PNI. Interestingly, compared with patients with better nutritional status, chemotherapy was significantly associated with poorer OS in malnourished oral cancer patients. CONCLUSIONS: BMI, ALB, PNI and NRI are of prognostic value in patients with oral cancer and the prognostic performance of NRI was superior to BMI or ALB or PNI. Malnutrition (BMI < 18.5 kg/m2 or ALB< 40 g/l or PNI < 49.3 or NRI < 97.5) could predict an unfavorable response to chemotherapy in oral cancer patients.

In Vitro Assessment of Antitumor Potential and Combination Effect of Classical and Molecular-targeted Anticancer Drugs.

BACKGROUND/AIM: The aim of the study was to evaluate the antitumor potential and combination effects of chemotherapeutic drugs. MATERIALS AND METHODS: The cytotoxicity of 20 drip-type classical and molecular-targeted anticancer drugs was examined against 4 human oral squamous cell carcinoma cell lines and 5 human oral normal mesenchymal and epithelial cells. Cell cycle progression was monitored by a cell sorter. Combination effect was evaluated by combination index. RESULTS: Most of the classical anticancer drugs showed much higher antitumor activity than molecular-targeted drugs, except bortezomib. Among 12 classical anticancer drugs, taxanes and gemsitabine showed the highest tumor-specificity (TS) and potency-selectivity expression (PSE) values, whereas platinum analogs showed the least TS value. Combination of two classical or a classical and a molecular-targeted drug showed mostly additive or antagonistic effect. 5-FU and cisplatin did not produce a subG1 population, but induced G2/M or G1/S arrest, regardless of the addition of cetuximab. Cetuximab, nibolumab and bortezomib showed potent keratinocyte toxicity. CONCLUSION: The present TS monitoring system may provide useful information for building up the treatment regimens of anticancer drugs.

Platform for ergonomic intraoral photodynamic therapy using low-cost, modular 3D-printed components: Design, comfort and clinical evaluation.

Oral cancer prevalence is increasing at an alarming rate worldwide, especially in developing countries which lack the medical infrastructure to manage it. For example, the oral cancer burden in India has been identified as a public health crisis. The high expense and logistical barriers to obtaining treatment with surgery, radiotherapy and chemotherapy often result in progression to unmanageable late stage disease with high morbidity. Even when curative, these approaches can be cosmetically and functionally disfiguring with extensive side effects. An alternate effective therapy for oral cancer is a light based spatially-targeted cytotoxic therapy called photodynamic therapy (PDT). Despite excellent healing of the oral mucosa in PDT, a lack of robust enabling technology for intraoral light delivery has limited its broader implementation. Leveraging advances in 3D printing, we have developed an intraoral light delivery system consisting of modular 3D printed light applicators with pre-calibrated dosimetry and mouth props that can be utilized to perform PDT in conscious subjects without the need of extensive infrastructure or manual positioning of an optical fiber. To evaluate the stability of the light applicators, we utilized an endoscope in lieu of the optical fiber to monitor motion in the fiducial markers. Here we showcase the stability (less than 2 mm deviation in both horizontal and vertical axis) and ergonomics of our applicators in delivering light precisely to the target location in ten healthy volunteers. We also demonstrate in five subjects with T1N0M0 oral lesions that our applicators coupled with a low-cost fiber coupled LED-based light source served as a complete platform for intraoral light delivery achieving complete tumor response with no residual disease at initial histopathology follow up in these patients. Overall, our approach potentiates PDT as a viable therapeutic option for early stage oral lesions that can be delivered in low resource settings.

Assessment of the Blood Parameters, Cardiac and Liver Enzymes in Oral Squamous Cell Carcinoma Following Treated with Injectable Doxorubicin-Loaded Nano-Particles.

Purpose: Oral squamous cell carcinoma (OSCC) is the most common and most malignant disorder of the oral cavity. Standard cancer treatments have many complications for patients. Nausea, vomiting, and perturbation in blood cells are the most common side effects when using Doxorubicin (Dox) for the treatment of OSCC. Use of Doxorubicin-loaded nano-particles (n-Dox) give rise to increase its biological efficacy and the rapeutic effects. This study assessed the efficacy of the injectable form of the n-Doxon blood parameters and cardiac and liver enzymes compared to the commercial form of Dox in OSCC-induced by 4NQO in rats. Methods: 4-nitroquinoline-1-oxideas was used as a solution in drinking water for inducing OSCC during 14 weeks in male Sprague-Dawley rats. Four groups of animals were categorized randomly: first (OSCC+Dox), second (OSCC+n-Dox), third (OSCC) and, last, healthy animals. Results: Using n-Dox had no harmful effect on the number of white and red blood cells. Thrombocytopenia and leukopenia in animals treated with n-Dox was less than the other groups. Hemoglobin and hematocrit in all treated groups did not differ and were similar to the healthy control. Hepatic and cardiac enzymes did not show any significant difference in any of the groups. Conclusion: The results of this research showed that significant decreases in haematological changes occurred, including leukopenia and anemia, in an animal model of OSCC induced by 4-NQO following use of n-Dox with compare to Dox. Use of n-Dox is better than of Dox for treatment of OSCC.

Assessment of zero-valent iron-based nanotherapeutics for ferroptosis induction and resensitization strategy in cancer cells.

Addressing nanomedicine resistance is critical for its ultimate clinical success; despite this, advancing the therapeutic designs for cancer therapy are rarely discussed in the literature. In this study, we discovered that ferroptosis is the central mechanism governing the therapeutic efficacy and resistance of treatment with zero-valent iron nanoparticles (ZVI NPs). In ZVI-sensitive oral cancer cells, ZVI NPs-induced ferroptosis was characterized by mitochondrial lipid peroxidation and reduced levels of glutathione peroxidases (GPx) in subcellular organelles. However, resistant cells could attenuate ZVI-induced oxidative stress and GPx reduction. They also showed stronger mitochondrial respiration ability, thus resisting ZVI NPs-induced mitochondrial membrane potential loss. Transcriptome comparison and quantitative polymerase chain reaction (qPCR) analysis revealed that ZVI-resistant cancer cells expressed a gene set related to enhanced NADPH supply, higher detoxification capacity of reactive oxygen species, and decreased sensitivity to ferroptosis inducers (FINs). Finally, we discovered that certain FINs were able to sensitize ZVI-resistant cancer cells to become treatable without compromising healthy non-malignant cells. These findings suggest that ferroptosis can serve as a druggable target for anti-cancer nanomedicine and therapeutic resistance modulation using ZVI NPs.

Development and evaluation of a low-cost, portable, LED-based device for PDT treatment of early-stage oral cancer in resource-limited settings.

BACKGROUND: Photodynamic therapy (PDT) using δ-aminolevulinic acid (ALA) photosensitization has shown promise in clinical studies for the treatment of early-stage oral malignancies with fewer potential side effects than traditional therapies. Light delivery to oral lesions can also carried out with limited medical infrastructure suggesting the potential for implementation of PDT in global health settings. OBJECTIVES: We sought to develop a cost-effective, battery-powered, fiber-coupled PDT system suitable for intraoral light delivery enabled by smartphone interface and embedded electronics for ease of operation. METHODS: Device performance was assessed in measurements of optical power output, spectral stability, and preclinical assessment of PDT response in ALA-photosensitized squamous carcinoma cell cultures and murine subcutaneous tumor xenografts. RESULTS: The system achieves target optoelectronic performance with a stable battery-powered output of approximately 180 mW from the fiber tip within the desired spectral window for PpIX activation. The device has a compact configuration, user friendly operation and flexible light delivery for the oral cavity. In cell culture, we show that the overall dose-response is consistent with established light sources and complete cell death of ALA photosensitized cells can be achieved in the irradiated zone. In vivo PDT response (reduction in tumor volume) is comparable with a commercial 635 nm laser. CONCLUSIONS: We developed a low-cost, LED-based, fiber-coupled PDT light delivery source that has stable output on battery power and suitable form factor for deployment in rural and/or resource-limited settings. Lasers Surg. Med. 9999:1-7, 2018. © 2018 Wiley Periodicals, Inc.

Assessment of Anti-carcinogenic Effect of Pomegranate in Oral Squamous Cell Carcinoma (Pre-clinical Study).

BACKGROUND AND OBJECTIVE: The survival portion of patients treated from oral cancer isn't in progress. This is why researchers are continuously looking for new anti-cancer drugs either natural product or natural product derivatives. Studies have shown that pomegranate and its constituents might have an anti-tumorigenic effect. So the aim of this study was to assess the anticarcinogenic roles of pomegranate on oral squamous cell carcinoma as an adjuvant of chemotherapy. MATERIALS AND METHODS: The Hep-2 cells were propagated and maintained under basic culture media. Cells were grouped according to culture media and each group was tested for cell proliferation as well as VEGF expression and caspase-3 expressions using ELISA and RT-PCR, respectively. RESULTS: Regarding cell proliferation and VEGF expression, a higher mean value was recorded in group 1 in comparison to group 3 with a significant difference (p = 0.001) and in group 2 in comparison to group 4, with a significant difference (p = 0.049). While concerning caspase-3 expression, a higher mean value was recorded in group 3 in comparison to group 1 with a significant difference (p = 0.045) and in group 4 in comparison to group 2, with a significant difference (p = 0.00). CONCLUSION: Pomegranate can be an adjuvant, natural product for oral cancer treatment in combination with 5-fluorouracil to reduce its dose and nullify its toxic side effects on normal body organs.

Patients' Perception of App-based Educational and Behavioural Interventions for Enhancing Oral Anticancer Medication Adherence.

Well-designed smartphone apps can potentially help in enhancing adherence to oral anticancer medications (OAMs). The objective of this study was to evaluate patients' perception on inclusion of various adherence-enhancing strategies as features of an app and their interest in using such app. A cross-sectional survey was conducted at the National Cancer Centre Singapore. A structured self-administered questionnaire was used to collect data from patients taking OAMs. Final analysis was based on 409 surveys and most of the respondents were female (291, 71.1%), Chinese (332, 81.2%), married (296, 72.4%) and breast cancer patients (211, 51.6%). Close to two-thirds of respondents rated medication information (65.0%), disease information (60.2%) and side effect self-management (60.2%) features as having the highest level of importance in an adherence app. Three hundred thirty-two (81.2%) of the respondents owned a smartphone, among which 92 (27.7%) reported using health-related apps. From respondents with smartphones, 219 (66.0%) were interested in using an app for OAM adherence. Age 65 and older compared to 21-54 years old (adjusted OR = 0.34; 95% CI = 0.15-0.76) and current use of a health app (adjusted OR = 1.91; 95% CI = 1.07-3.41) were significant predictors of interest to adopt an adherence app. In conclusion, patients value the inclusion of educational and behavioural interventions in adherence apps. Developers of adherence apps should consider including tools for side effect self-management and provision of information to educate patients on their medications and disease condition.

Antitumor activity of 4-O-Methylhonokiol in human oral cancer cells is mediated via ROS generation, disruption of mitochondrial potential, cell cycle arrest and modulation of Bcl-2/Bax proteins.

PURPOSE: The plant-derived natural product 4-O-methylhonokiol (MH) has been reported to possess tremendous pharmacological potential ranging from neuroprotection to anticancer activity. However, the anticancer activity of MH in oral squamous cell carcinoma (OSCC) cells has not been evaluated. In the present study, MH was evaluated for its anticancer activity against OSSC PE/CA-PJ41 cells and the possible underlying mechanism was determined. METHODS: Cell cytotoxicity was evaluated by colorimetrybased MTT assay while the effects on cell cycle phase distribution were assessed by flow cytometry. Effects of MH on reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were evaluated by flow cytometry. Western blot assay was finally utilized to study the effects of MH on key cancer and apoptosis-linked proteins including Bax and Bcl-2. RESULTS: MH induced cytotoxicity in OSCC PE/CA-PJ41 cells with an observed IC50 of 1.25 µM. It also caused significant increase in the production of ROS and disrupted the MMP in a dose-dependent manner. The reduction in MMP favored mitochondrial apoptotic pathway which was further confirmed by determining the expression of Bax and Bcl-2. It was observed that MH downregulated the expression of Bax and upregulated the expression of MMP, ultimately leading to apoptosis of OSSC PE/CA-PJ41 cells. Additionally, MH also caused G2/M cell cycle arrest in a dose-dependent manner. CONCLUSION: Taken together, our results indicate that 4-Omethylhonokiol may prove a potential natural anticancer molecule against human oral carcinoma cells.

Medication adherence to oral cancer therapy: The promising role of the pharmacist.

Medication adherence to oral cancer therapy is a critical component to achieving optimal patient outcomes. As the US population ages, growing numbers of patients will be prescribed oral cancer therapy regimens, highlighting the need for innovative and scalable solutions. Clinical pharmacists offer tremendous promise to help patients improve their adherence to oral cancer therapy. Moreover, addition of oral chemotherapy to Centers for Medicare & Medicaid Services (CMS) medication adherence quality measures has the potential to improve care and result in better therapeutic outcomes with fewer costs for patients and payers. Future research is needed to test the use of pharmacist-managed interventions to improve adherence to oral cancer therapy.

Tolerance and toxicity of neoadjuvant docetaxel, cisplatin and 5 fluorouracil regimen in technically unresectable oral cancer in resource limited rural based tertiary cancer center.

BACKGROUND: Recent studies indicate neoadjuvant chemotherapy (NACT) can result in R0 resection in a substantial proportion of patients with technically unresectable oral cavity cancers. However, data regarding the efficacy and safety of docetaxel, cisplatin and 5 fluorouracil (TPF) NACT in our setting is lacking. The present audit was proposed to evaluate the toxicities encountered during administration of this regimen. It was hypothesized that TPF NACT would be considered feasible for routine administration if an average relative dose intensity (ARDI) of ≥0.90 or more in at least 70% of the patients. MATERIALS AND METHODS: Technically unresectable oral cancers with Eastern Cooperative Oncology Group PS 0-2, with biopsy proven squamous cell carcinoma underwent two cycles of NACT with TPF regimen. Toxicity and response rates were noted following the CTCAE 4.03 and RECIST criteria. Descriptive analysis of completion rates (completing 2 cycles of planned chemotherapy with ARDI of 0.85 or more), reason for delay, toxicity, and response are presented. RESULTS: The NACT was completed by all patients. The number of subjects who completed all planned cycles of chemotherapy are with the ARDI of the delivered chemotherapy been equal to or >0.85 was 11 (91.67%). All toxicity inclusive Grade 3-5 toxicity was seen in 11 patients (91.67%). The response rate of chemotherapy was 83.33%. There were three complete response, seven partial response, and two stable disease seen post NACT in this study. CONCLUSION: Docetaxel, cisplatin and 5 fluorouracil regimen can be routinely administered at our center with the supportive care methods and precautionary methods used in our study.

Out-of-pocket costs and oral cancer medication discontinuation in the elderly.

BACKGROUND: Cancer is a major cause of mortality and a major contributor to health care costs in the United States. An increasing number of cancer patients are treated with oral cancer therapy. Older patients are more likely to have cancer and to be at risk for adherence problems with oral cancer drugs. As a result of substantial cost sharing required for oral cancer drugs and the possibility of early entry into the Medicare Part D coverage gap, high out-of-pocket (OOP) drug costs could put elderly beneficiaries at great risk for delaying or discontinuing their cancer therapies. OBJECTIVES: To (a) determine the OOP costs of oral cancer treatment and the numbers of patients that delay or discontinue oral cancer therapy and (b) examine the relationship between OOP costs and medication discontinuation or delay among older Medicare beneficiaries. METHODS: A cross-sectional study was conducted using a 5% sample of Medicare beneficiaries who filled a prescription for imatinib, erlotinib, anastrozole, letrozole, or thalidomide during 2008. Patients included in the analysis sample did not receive drug subsidies, were aged 65 years or older, and were enrolled in Medicare Part D for all 12 months of 2008. Logistic regression was used to determine the association between OOP costs and medication discontinuation or delay. RESULTS: Mean OOP costs per day were $2.96 for anastrozole, $3.10 for letrozole, $22.90 for imatinib, $28.35 for erlotinib, and $37.47 for thalidomide. The percentages of patients who discontinued or delayed oral cancer therapy were 58% for anastrozole, 64% for letrozole, 35% for imatinib, 61% for erlotinib, and 70% for thalidomide. For each $10 increase in OOP spending per month, the likelihood of discontinuation or delay increased 13%, 14%, and 20% for imatinib, erlotinib, and thalidomide users, respectively, but decreased 26% for anastrozole and letrozole users.  CONCLUSION: Beneficiaries with higher OOP costs for the more expensive oral cancer drugs were more likely to discontinue or delay drug therapy.