Purine Nucleoside Phosphorylase mediated molecular chemotherapy and conventional chemotherapy: A tangible union against chemoresistant cancer

Background Late stage Ovarian Cancer is essentially incurable primarily due to late diagnosis and its inherent heterogeneity. Single agent treatments are inadequate and generally lead to severe side effects at therapeutic doses. It is crucial to develop clinically relevant novel combination regimens involving synergistic modalities that target a wider repertoire of cells and lead to lowered individual doses. Stemming from this premise, this is the first report of two- and three-way synergies between Adenovirus-mediated Purine Nucleoside Phosphorylase based gene directed enzyme prodrug therapy (PNP-GDEPT), docetaxel and/or carboplatin in multidrug-resistant ovarian cancer cells. Methods The effects of PNP-GDEPT on different cellular processes were determined using Shotgun Proteomics analyses. The in vitro cell growth inhibition in differentially treated drug resistant human ovarian cancer cell lines was established using a cell-viability assay. The extent of synergy, additivity, or antagonism between treatments was evaluated using CalcuSyn statistical analyses. The involvement of apoptosis and implicated proteins in effects of different treatments was established using flow cytometry based detection of M30 (an early marker of apoptosis), cell cycle analyses and finally western blot based analyses. Results Efficacy of the trimodal treatment was significantly greater than that achieved with bimodal- or individual treatments with potential for 10-50 fold dose reduction compared to that required for individual treatments. Of note was the marked enhancement in apoptosis that specifically accompanied the combinations that included PNP-GDEPT and accordingly correlated with a shift in the expression of anti- and pro-apoptotic proteins. PNP-GDEPT mediated enhancement of apoptosis was reinforced by cell cycle analyses. Proteomic analyses of PNP-GDEPT treated cells indicated a dowregulation of proteins involved in oncogenesis or cancer drug resistance in treated cells with accompanying upregulation of apoptotic- and tumour- suppressor proteins. Conclusion Inclusion of PNP-GDEPT in regular chemotherapy regimens can lead to significant enhancement of the cancer cell susceptibility to the combined treatment. Overall, these data will underpin the development of regimens that can benefit patients with late stage ovarian cancer leading to significantly improved efficacy and increased quality of life.

Ginger (Zingiber officinale) and chemotherapy-induced nausea and vomiting : a systematic literature review

Chemotherapy-induced nausea and vomiting (CINV) is a common side-effect of cytotoxic treatment. It continues to affect a significant proportion of patients despite the widespread use of anti-emetic medication. In folk-medicine, ginger (Zingiber officinale) has been used to prevent and treat nausea in many cultures for thousands of years. However, its use has not been validated in the chemotherapy context. To determine the potential use of ginger as a prophylactic or treatment of CINV, a systematic literature review was conducted. Reviewed studies comprised randomised controlled trials or cross-over trials that investigated the anti-CINV effect of ginger as the sole intervention independent variable in chemotherapy patients. Seven studies met the inclusion criteria. All studies were assessed on methodological quality and their limitations were identified. Studies were mixed in their support of ginger as an anti-CINV treatment in patients receiving chemotherapy, with three demonstrating a positive effect, two in favour but with caveats and two showing no effect on measures of CINV. Future studies are required to address the limitations identified before clinical use can be recommended.

Nutrition screening and risk factors prior to chemotherapy in cancer patients 65 years and older

Background The largest proportion of cancer patients are aged 65 years and over. Increasing age is also associated with nutritional risk and multi-morbidities—factors which complicate the cancer treatment decision-making process in older patients. Objectives To determine whether malnutrition risk and Body Mass Index (BMI) are associated with key oncogeriatric variables as potential predictors of chemotherapy outcomes in geriatric oncology patients with solid tumours. Methods In this longitudinal study, geriatric oncology patients (aged ≥65 years) received a Comprehensive Geriatric Assessment (CGA) for baseline data collection prior to the commencement of chemotherapy treatment. Malnutrition risk was assessed using the Malnutrition Screening Tool (MST) and BMI was calculated using anthropometric data. Nutritional risk was compared with other variables collected as part of standard CGA. Associations were determined by chi-square tests and correlations. Results Over half of the 175 geriatric oncology patients were at risk of malnutrition (53.1%) according to MST. BMI ranged from 15.5–50.9kg/m2, with 35.4% of the cohort overweight when compared to geriatric cutoffs. Malnutrition risk was more prevalent in those who were underweight (70%) although many overweight participants presented as at risk (34%). Malnutrition risk was associated with a diagnosis of colorectal or lung cancer (p=0.001), dependence in activities of daily living (p=0.015) and impaired cognition (p=0.049). Malnutrition risk was positively associated with vulnerability to intensive cancer therapy (rho=0.16, p=0.038). Larger BMI was associated with a greater number of multi-morbidities (rho =.27, p=0.001. Conclusions Malnutrition risk is prevalent among geriatric patients undergoing chemotherapy, is more common in colorectal and lung cancer diagnoses, is associated with impaired functionality and cognition and negatively influences ability to complete planned intensive chemotherapy.

Engineering the fitness of older patients for chemotherapy : an exploration of Comprehensive Geriatric Assessment in practice

Clinicians often report that currently available methods to assess older patients, including standard clinical consultations, do not elicit the information necessary to make an appropriate cancer treatment recommendation for older cancer patients. An increasingly popular way of assessing the potential of older patients to cope with chemotherapy is a Comprehensive Geriatric Assessment. What constitutes Comprehensive Geriatric Assessment, however, is open to interpretation and varies from one setting to another. Furthermore, Comprehensive Geriatric Assessment’s usefulness as a predictor of fitness for chemotherapy and as a determinant of actual treatment is not well understood. In this article, we analyse how Comprehensive Geriatric Assessment was developed for use in a large cancer service in an Australian capital city. Drawing upon Actor–Network Theory, our findings reveal how, during its development, Comprehensive Geriatric Assessment was made both a tool and a science. Furthermore, we briefly explore the tensions that we experienced as scholars who analyse medico-scientific practices and as practitioner–designers charged with improving the very tools we critique. Our study contributes towards geriatric oncology by scrutinising the medicalisation of ageing, unravelling the practices of standardisation and illuminating the multiplicity of ‘fitness for chemotherapy’.

Malnutrition and chemotherapy : implications for nursing practice

Background: Malnutrition before and during chemotherapy is associated with poor treatment outcomes. The risk of cancer-related malnutrition is exacerbated by common nutrition impact symptoms during chemotherapy, such as nausea, diarrhoea and mucositis. Aim of presentation: To describe the prevalence of malnutrition/ malnutrition risk in two samples of patients treated in a quaternary-level chemotherapy unit. Research design: Cross sectional survey. Sample 1: Patients ≥ 65 years prior to chemotherapy treatment (n=175). Instrument: Nurse-administered Malnutrition Screening Tool to screen for malnutrition risk and body mass index (BMI). Sample 2: Patients ≥ 18 years receiving chemotherapy (n=121). Instrument: Dietitian-administered Patient Generated Subjective Global Assessment to assess malnutrition, malnutrition risk and BMI. Findings Sample 1: 93/175 (53%) of older patients were at risk of malnutrition prior to chemotherapy. 27 (15%) were underweight (BMI <21.9); 84 (48%) were overweight (BMI >27). Findings Sample 2: 31/121 patients (26%) were malnourished; 12 (10%) had intake-limiting nausea or vomiting; 22 (20%) reported significant weight loss; and 20 (18%) required improved nutritional symptom management during treatment. 13 participants with malnutrition/nutrition impact symptoms (35%) had no dietitian contact; the majority of these participants were overweight. Implications for nursing: Patients with, or at risk of, malnutrition before and during chemotherapy can be overlooked, particularly if they are overweight. Older patients seem particularly at risk. Nurses can easily and quickly identify risk with the regular use of the Malnutrition Screening Tool, and refer patients to expert dietetic support, to ensure optimal treatment outcomes.

Predicting fitness for chemotherapy in older cancer patients

Background: The Vulnerable Elders Survey-13 (VES-13) is increasingly used to screen for older patients who can proceed to intensive chemotherapy without further comprehensive assessment. This study compared the VES-13 determination of fitness for treatment with the oncologist's assessments of fitness. Method: Sample: Consecutive series of solid tumour patients ≥65 years (n=175; M=72; range=65-86) from an Australian cancer centre. Patients were screened with the VES-13 before proceeding to usual treatment. Blinded to screening, oncologists concurrently predicted patient fitness for chemotherapy. A sample of 175 can detect, with 90% power, kappa coefficients of agreement between VES-13 and oncologists’ assessments >0.90 ("almost perfect agreement"). Separate backward stepwise logistic regression analyses assessed potential predictors of VES-13 and oncologists’ ratings of fitness. Results: Kappa coefficient for agreement between VES-13 and oncologists’ ratings of fitness was 0.41 (p<0.001). VES-13 and oncologists’ assessments agreed in 71% of ratings. VES-13 sensitivity = 83.3%; specificity = 57%; positive predictive value = 69%; negative predictive value = 75%. Logistic regression modelling indicated that the odds of being vulnerable to chemotherapy (VES-13) increased with increasing depression (OR=1.42; 95% CI: 1.18, 1.71) and decreased with increased functional independence assessed on the Bartel Index (OR=0.82; CI: 0.74, 0.92) and Lawton instrumental activities of daily living (OR=0.44; CI: 0.30, 0.65); RSquare=.65. Similarly, the odds of a patient being vulnerable to chemotherapy, when assessed by physicians, increased with increasing age (OR=1.15; CI: 1.07, 1.23) and depression (OR=1.23; CI: 1.06, 1.43), and decreased with increasing functional independence (OR=0.91; CI: 0.85, 0.98); RSquare=.32. Conclusions: Our data indicate moderate agreement between VES-13 and clinician assessments of patients’ fitness for chemotherapy. Current ‘one-step’ screening processes to determine fitness have limits. Nonetheless, screening tools do have the potential for modification and enhanced predictive properties in cancer care by adding relevant items, thus enabling fit patients to be immediately referred for chemotherapy.

Comprehensive assessment of the fitness of older people for chemotherapy

Purpose: To present the results of a mixed-method study comparing the level of agreement of a two-phased, nurse-administered Comprehensive Geriatric Assessment (CGA) with current methods that assess the fitness for chemotherapy of older cancer patients. A nurse-led model of multidisciplinary cancer care based on the results is also described. Methods: The two phases comprised initial screening by a nurse with the Vulnerable Elders Survey-13 [VES-13], followed by nurse administration of a detailed CGA. Both phases were linked to a computerised algorithm categorising the patient as ‘fit’, ‘vulnerable’ or ‘frail’. The study determined the level of agreement between VES-13- and CGA-determined categories; and between the CGA and the physicians’ assessments. It also compared the CGA’s predictive abilities in terms of subsequent treatment toxicity; while interviews determined the acceptability of the nurse-led procedure from key stakeholders' perspectives. Results: Data collection was completed in December 2011. The results will be presented at the conference. A consecutive-series n=170 will be enrolled, 33% of whom are ‘fit’; 33% ‘vulnerable’; and 33% ‘too frail’ for treatment. This sample can detect, with 90% power, kappa coefficients of agreement of ≥ 0.70 or higher (“substantial agreement”). Fitness sub-group comparisons of agreement between the medical oncologist and the nurse assessments can detect kappa estimates of Κ ≥ 0.80 with the same power. Conclusion: The results have informed a nurse-led model of cancer care. It meets a clear need to develop, implement and test a nurse-led, robust, evidence-based, clinically-justifiable and economically-feasible CGA process that has relevance in national and international contexts.

Fatigue self-management : a survey of Chinese cancer patients undergoing chemotherapy

Aims and objectives. To examine Chinese cancer patients’ fatigue self-management, including the types of self-management behaviours used, their confidence in using these behaviours, the degree of relief obtained and the factors associated with patients’ use of fatigue self-management behaviours. Background. Fatigue places significant burden on patients with cancer undergoing chemotherapy. While some studies have explored fatigue self-management in Western settings, very few studies have explored self-management behaviours in China. Design. Cross-sectional self- and/or interviewer-administered survey. Methods. A total of 271 participants with self-reported fatigue in the past week were recruited from a specialist cancer hospital in south-east China. Participants completed measures assessing the use of fatigue self-management behaviours, corresponding self-efficacy, perceived relief levels plus items assessing demographic characteristics, fatigue experiences, distress and social support. Results. A mean of 4_94 (_2_07; range 1–10) fatigue self-management behaviours was reported. Most behaviours were rated as providing moderate relief and were implemented with moderate self-efficacy. Regression analyses identified that having more support from one’s neighbourhood and better functional status predicted the use of a greater number of self-management behaviours. Separate regression analyses identified that greater neighbourhood support predicted greater relief from ‘activity enhancement behaviours’ and that better functional status predicted greater relief from ‘rest and sleep behaviours’. Higher self-efficacy scores predicted greater relief from corresponding behaviours. Conclusions. A range of fatigue self-management behaviours were initiated by Chinese patients with cancer. Individual, condition and environmental factors were found to influence engagement in and relief from fatigue self-managementbehaviours. Relevance to clinical practice. Findings highlight the need for nurses to explore patients’ use of fatigue self-management behaviours and the effectiveness of these behaviours in reducing fatigue. Interventions that improve patients’ self-efficacy and neighbourhood supports have the potential to improve outcomes from fatigue self-management behaviours.

Self-management of chemotherapy-related nausea and vomiting : a cross-sectional survey of Chinese cancer patients

BACKGROUND Chemotherapy-induced nausea and vomiting (CINV) remain prevalent among cancer patients despite pharmacological advances in CINV therapy. Patients can initiate nonpharmacologic strategies, which potentially play an important role as adjuncts to pharmacological agents in alleviating CINV. Some studies have explored nausea and vomiting self-management (NVSM) behaviors among patients in Western settings; however, little is known about the NVSM behaviors of patients in China. OBJECTIVES This study examines NVSM behaviors of Chinese cancer patients. METHODS A cross-sectional survey was conducted in a specialist cancer hospital in southeast China. RESULTS A sample of 255 cancer patients was recruited. A mean of 8.56 (±3.15) NVSM behaviors was reported. Most NVSM behaviors were rated as moderately effective and were implemented with moderate self-efficacy. Higher distress levels, better functional status, previous similar symptom experiences, receiving chemotherapy as an inpatient, and greater support from multiple levels were related to greater engagement in NVSM; higher self-efficacy levels pertaining to NVSM behaviors were associated with reports of more relief from specific NVSM behaviors. CONCLUSIONS A range of NVSM strategies was initiated by Chinese cancer patients and provided some relief. A range of individual, health status, and environmental factors influenced engagement with and relief from NVSM behaviors. IMPLICATIONS FOR PRACTICE To enhance Chinese patients' NVSM, patients should be supported to engage in behaviors including taking antiemetics, modifying their diet, using psychological strategies, and creating a pleasant environment. The findings highlight the importance of enhancing patients' self-efficacy in NVSM, alleviating symptom distress, and improving social support to achieve better outcomes.