Best Evidence to Best Practice: Implementing an Innovative Model of Nutrition Care for Patients with Head and Neck Cancer Improves Outcomes.

Malnutrition is prevalent in patients with head and neck cancer (HNC), impacting outcomes. Despite publication of nutrition care evidence-based guidelines (EBGs), evidence-practice gaps exist. This study aimed to implement and evaluate the integration of a patient-centred, best-practice dietetic model of care into an HNC multidisciplinary team (MDT) to minimise the detrimental sequelae of malnutrition. A mixed-methods, pre-post study design was used to deliver key interventions underpinned by evidence-based implementation strategies to address identified barriers and facilitators to change at individual, team and system levels. A data audit of medical records established baseline adherence to EBGs and clinical parameters prior to implementation in a prospective cohort. Key interventions included a weekly Supportive Care-Led Pre-Treatment Clinic and a Nutrition Care Dashboard highlighting nutrition outcome data integrated into MDT meetings. Focus groups provided team-level evaluation of the new model of care. Economic analysis determined system-level impact. The baseline clinical audit (n = 98) revealed barriers including reactive nutrition care, lack of familiarity with EBGs or awareness of intensive nutrition care needs as well as infrastructure and dietetic resource limitations. Post-implementation data (n = 34) demonstrated improved process and clinical outcomes: pre-treatment dietitian assessment; use of a validated nutrition assessment tool before, during and after treatment. Patients receiving the new model of care were significantly more likely to complete prescribed radiotherapy and systemic therapy. Differences in mean percentage weight change were clinically relevant. At the system level, the new model of care avoided 3.92 unplanned admissions and related costs of $AUD121K per annum. Focus groups confirmed clear support at the multidisciplinary team level for continuing the new model of care. Implementing an evidence-based nutrition model of care in patients with HNC is feasible and can improve outcomes. Benefits of this model of care may be transferrable to other patient groups within cancer settings.

Synthesis of a monofunctional platinum compound and its activity alone and in combination with phytochemicals in ovarian tumor models.

Currently used platinum drugs fail to provide long-term cure for ovarian cancer mainly because of acquired drug resistance. In this study, a new monofunctional planaramineplatinum(II) complex, namely tris(8-hydroxyquinoline)monochloroplatinum(II) chloride (coded as LH3), was synthesised and investigated for its activity against human ovarian A2780, cisplatin-resistant A2780 (A2780(cisR)) and ZD0473-resistant A2780 (A2780(ZD0473R)) cancer cell lines, alone and in combination with the phytochemicals curcumin, genistein and resveratrol. Cellular levels of glutathione in A2780 and A2780(cisR) cell lines before and after treatment with LH3 and its combinations with genistein and curcumin were also determined. Interaction of the compounds with salmon sperm DNA, pBR322 plasmid DNA and damage to DNA in A2780 and A2780(cisR) cells due to interaction with LH3-alone and in combination with phytochemicals were also investigated. LH3 was found to be much more active than cisplatin against the resistant tumor models and greatest synergism in activity was observed when combinations of LH3 with genistein and curcumin were administered as a bolus. For combinations of LH3 with the phytochemicals, platinum accumulation and the level of Pt-DNA binding were found to be greater in the resistant A2780(cisR) cell line than in the parental A2780 cell line. Greater activity of LH3 than cisplatin against the resistant ovarian cell lines indicates that it may have the potential for development as a novel anticancer drug and that its combination with phytochemicals can serve to further enhance drug efficacy.

Investigation of herb-drug interactions with ginkgo biloba in women receiving hormonal treatment for early breast cancer.

Women receiving treatment for breast cancer commonly ingest herbal medicines. Little is known about the potential for herb-drug interactions in this population. The aim of this study is to investigate the effect of ginkgo biloba co-administration on the pharmacokinetics of tamoxifen, anastrozole and letrozole. This was a prospective open-label cross-over study in 60 women with early stage breast cancer taking either tamoxifen, anastrozole or letrozole (n=20/group). Participants received ginkgo biloba (EGb 761) for 3 weeks (120 mg twice daily). Trough concentrations of drugs were measured before and after ginkgo biloba treatment using LC-MS/MS. Toxicities were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events. Trough concentrations before and after treatment with ginkgo biloba were not significantly different for tamoxifen (93.5 ± 29.0, 86.5 ± 25.3 ng/mL; p=0.16), letrozole (91.1 ± 50.4, 89.6 ± 52.14 ng/mL; p=0.60) or anastrozole (29.1 ± 8.6, 29.1 ± 7.6 ng/mL; p=0.97). Ginkgo biloba was well tolerated, with no difference in toxicity during ginkgo biloba. Co-administration of ginkgo biloba does not significantly affect the pharmacokinetics of tamoxifen, anastrozole or letrozole. There was no difference in the toxicity profile of hormone therapy with ginkgo biloba use in women with early stage breast cancer.

Studies on combination of platinum drugs cisplatin and oxaliplatin with phytochemicals anethole and curcumin in ovarian tumour models.

Chemopreventative phytochemicals having antitumour and antioxidant properties can overcome problems of chemoresistance and nonspecific toxicity towards normal cells that are associated with platinum-based chemotherapy against cancer. These agents exert their effects by bringing into play numerous cellular proteins that in turn affect multiple steps in pathways leading to tumourigenesis. In this study, combinations of two cytotoxic phytochemicals anethole and curcumin were applied in binary combination with platinum drugs cisplatin and oxaliplatin to three epithelial ovarian cancer cell lines: A2780 (parent), A2780(cisR) (cisplatin-resistant) and A2780(ZD0473R) (ZD0473-resistant). Cell viability was quantified using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) reduction assay and the combined drug action was analyzed based on the equations derived by Chou and Talalay (1984). Greatest synergism was observed when the phytochemical was added first followed by the platinum drug 2 h later and additiveness to antagonism in combined drug action was observed when the two compounds were administered as a bolus. If confirmed in vivo, the appropriate sequenced combinations of platinum with the phytochemicals may provide a means of overcoming drug resistance.

Use of adjuvant chemotherapy in stage C (III) rectal cancer: comparison of data from matched patients in a teaching hospital's clinico-pathological database.

AIMS: Controversy continues regarding the treatment of patients with resectable rectal cancer, particularly in regard to the effects of adjuvant therapies on long-term survival. The benefits of adjuvant chemotherapy alone in patients with stage III rectal cancer after curative resection remain unclear. The aim of this study was to compare the overall survival of patients who had received adjuvant chemotherapy after resection of a stage III rectal cancer (111 patients) with the survival of a historical control group who had surgery alone before chemotherapy was introduced (129 patients). METHODS: Treatment and outcomes data were drawn from a prospective hospital registry of consecutive patients who had a resection for stage III rectal cancer. RESULTS: The estimated Kaplan-Meier overall 5-year survival rate in patients who received chemotherapy (68.7%, 95% CI 58.3-77.1%, log-rank P < 0.001) was improved compared with the historical controls (40.5%, 95% CI 31.4-49.5%, log-rank P < 0.001). No systematic differences between the treated and control group were found. CONCLUSION: This study has shown improved survival after adjuvant chemotherapy in patients with stage III rectal cancer as compared with historical controls treated by surgery alone. Hence, there could be subsets of patients whom when treated with surgery in a specialized surgical unit, may benefit from chemotherapy and spared the toxicities of adjuvant radiotherapy. This should be explored further in a cooperative trial group setting.

Effect of medical Qigong on cognitive function, quality of life, and a biomarker of inflammation in cancer patients: a randomized controlled trial.

PURPOSE: Cancer patients often experience diminished cognitive function (CF) and quality of life (QOL) due to the side effects of treatment and the disease symptoms. This study evaluates the effects of medical Qigong (MQ; combination of gentle exercise and meditation) on CF, QOL, and inflammation in cancer patients. METHODS: Eighty-one cancer patients recruited between October 2007 and May 2008 were randomly assigned to two groups: a control group (n = 44) who received the usual health care and an intervention group (n = 37) who participated in a 10-week MQ program. Self-reported CF was measured by the European Organization for Research and Treatment of Cancer (EORTC-CF) and the Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog). The Functional Assessment of Cancer Therapy-General (FACT-G) was used to measure QOL. C-reactive protein (CRP) was assessed as a biomarker of inflammation. RESULTS: The MQ group self-reported significantly improved CF (mean difference (MD) = 7.78, t (51) = -2.532, p = 0.014) in the EORTC-CF and all the FACT-Cog subscales [perceived cognitive impairment (MD = 4.70, t (43) = -2.254, p = 0.029), impact of perceived cognitive impairment on QOL (MD = 1.64, t (45) = -2.377, p = 0.024), and perceived cognitive abilities (MD = 3.61, t (45) = -2.229, p = 0.031)] compared to controls. The MQ group also reported significantly improved QOL (MD = 12.66, t (45) = -5.715, p < 0.001) and had reduced CRP levels (MD = -0.72, t (45) = 2.092, p = 0.042) compared to controls. CONCLUSIONS: Results suggest that MQ benefits cancer patients' self-reported CF, QOL, and inflammation. A larger randomized controlled trial including an objective assessment of CF is planned.

The use and perceived benefits resulting from the use of complementary and alternative medicine by cancer patients in Australia.

AIM: The use of complementary and alternative medicine (CAM) by cancer patients is growing. However, few studies have examined the perceived benefits and adverse effects resulting from the use of CAM by cancer patients. The aim of this study was to evaluate CAM use by cancer patients and to explore their perceptions of the benefit, safety and efficacy of CAM in general. METHODS: Oncologists from three university teaching hospitals screened patients for eligibility. Eligible patients (N = 1323) were mailed a letter of invitation with a questionnaire between January and May 2008. RESULTS: Overall 381 questionnaires were returned, showing that 65% of cancer patients used at least one form of CAM. Patients considered taking biological CAM before, during and after chemotherapy. Up to 90% of CAM users believed that CAM provided potential health benefits and less than 3% reported adverse effects experienced from the use of CAM. Most respondents (80%) believed CAM can provide health benefits even when efficacy has not been proven. Most patients (90%) believed that doctors should consider learning about CAM to provide appropriate advice to their cancer patients, and most (83%) indicated they would be happier to accept CAM if it was offered by the hospital. CONCLUSION: A substantial portion of Australian cancer patients use CAM. Given the limited data on efficacy and safety for most CAM, it may be reasonable to offer CAM within the hospital environment so its use can be monitored and patients can receive more evidence-based care.

Patient-doctor communication: use of complementary and alternative medicine by adult patients with cancer.

The purpose of this survey was to examine patient-doctor communication about the use of complementary and alternative medicine (CAM) by adult patients with cancer and compare patients' satisfaction with the consultation between patients who had and those who had not discussed the use of CAM with their doctors. Oncologists from three hospitals screened patients for eligibility. Eligible patients were mailed a letter of invitation with a questionnaire (N = 1,323). Three hundred eighty-one questionnaires were returned. Sixty-five percent of cancer patients used at least one form of CAM. Use of CAM was not discussed with the oncologist by 55% of respondents using biologically based CAM and by 80% of those using non-biologically based CAM since the diagnosis of cancer. Patients who discussed the use of biologic CAM with their oncologists were more satisfied with the consultation than those who had not (p = .027), whereas there were no significant differences between patients who discussed or did not discuss use of non-biologically based CAM (p = .102). A substantial proportion of cancer patients do not discuss the use of CAM with their oncologists. It is important to improve patient-doctor communication about the use of CAM to increase patients' satisfaction with the oncology consultation.

Nutrition intervention using an eicosapentaenoic acid (EPA)-containing supplement in patients with advanced colorectal cancer. Effects on nutritional and inflammatory status: a phase II trial.

GOALS: The aim of the study was to assess the impact of an eicosapentanoic acid-containing protein and energy dense oral nutritional supplement (EPA-ONS) on nutritional and inflammatory status, quality of life (QOL), plasma phospholipids (PPL) and cytokine profile, tolerance of irinotecan-containing chemotherapy and EPA-ONS in patients with advanced colorectal cancer (CRC) receiving chemotherapy. MATERIALS AND METHODS: Patients with advanced CRC having one prior chemotherapy regimen received 480 ml of EPA-ONS daily for 3 weeks before commencing chemotherapy with folinic acid, 5-fluorouracil, irinotecan (FOLFIRI), and continued for 3 cycles of treatment (9 weeks). All assessments including weight, body composition, C-reactive protein (CRP), QOL, dietary intake, PPL and cytokine analyses were performed at baseline, 3 and 9 weeks. RESULTS: Twenty-three patients were enrolled, 20 completed 3 weeks, and 15 completed 9 weeks. The mean EPA-ONS intake was 1.7 tetrapaks (408 ml) daily. There was a significant increase in mean weight (2.5 kg) at 3 weeks (p=0.03). Lean body mass (LBM) was maintained. Protein and energy intake significantly decreased after the commencement of chemotherapy (protein p=0.003, energy p=0.02). There was a significant increase in energy levels (p=0.03), whilst all other QOL measures were maintained. PPL EPA levels increased significantly over the first 3 weeks. Mean CRP increased by 14.9 mg/L over the first 3 weeks (p=0.004), but decreased to baseline levels by the end of the trial. There was a significant correlation between plasma IL-6 and IL-10 concentrations and survival, and between IL-12 and toxicity. CONCLUSION: Dietary counseling and the provision of EPA-ONS may result in maintenance of nutritional status and QOL, however randomized trials are required to evaluate the impact of EPA on toxicity from chemotherapy.

Malignant mixed mullerian tumour of the ovary: prognostic factor and response of adjuvant platinum-based chemotherapy.

OBJECTIVES: The purpose of the present study was to analyse retrospectively the data of a series of patients presenting to our unit with malignant mixed mullerian tumour (MMMT) of the ovary to identify the prognostic factors and relate them to survival. The role of platinum-based chemotherapy in the adjuvant treatment of this tumour was also evaluated. METHODS: All patients diagnosed with MMMT of the ovary from 1987 to 2000 were identified from the gynaecological tumour registry of King George V Hospital, Australia. The effect of clinical and histopathological variables on survival was analysed. The response of platinum-based adjuvant chemotherapy after surgery was also evaluated. RESULTS: Twenty patients with MMMT of the ovary were identified. Of the six patients with measurable disease, two (33%) had complete response after adjuvant platinum-based chemotherapy. The median survival of all patients was 8 months, while that of the patients receiving adjuvant platinum-based chemotherapy was 23 months. Women who were older (> 65 years) had a significantly worse survival rate than those who were younger (P = 0.02). The patients with optimal debulking had a better median survival than those with suboptimal debulking, but this difference was not statistically significant (P = 0.21). Sarcomatous component (homologous vs heterologous) was not found to be a significant prognostic factor for predicting survival. CONCLUSIONS: Malignant mixed mullerian tumour of the ovary is a rare and aggressive gynaecological tumour. The current study indicates that patient age was a significant prognostic factor for survival and surgical cytoreduction combined with platinum-based chemotherapy is the most effective management regimen identified to date to treat MMMT of the ovary.

A phase I trial of ZD9331, a water-soluble, nonpolyglutamatable, thymidylate synthase inhibitor.

PURPOSE: ZD9331 is a novel, direct-acting antifolate cytotoxic that does not require polyglutamation for activity, and is a specific thymidylate synthase inhibitor. This Phase I trial aimed to determine the maximum tolerated dose of ZD9331, given as a 30-min i.v. infusion on days 1 and 8 of a 21-day cycle. Pharmacokinetic parameters and tumor response were also assessed. EXPERIMENTAL DESIGN: A total of 71 patients, with a range of solid malignancies and refractory to standard therapies (44% had received > or =3 prior chemotherapy regimens), were treated. The most common malignancies were colorectal cancer (35% of patients) and ovarian cancer (31%). ZD9331 was escalated from 4.8 mg/m(2)/day. RESULTS: Dose-limiting toxicity occurred at 162.5 mg/m(2) ZD9331, with grade 4 thrombocytopenia, grade 4 neutropenia lasting > or =7 days, and grade 3 nonhematologic toxicity. Plasma clearance of ZD9331 was slow and dose-dependent; however, ZD9331 pharmacokinetics were nonlinear. Pharmacodynamics of ZD9331 were determined by measurement of plasma deoxyuridine, which increased at all of the dose levels; dose-related increases in plasma deoxyuridine were significant (P = 0.003) on day 5. Stable disease was observed in 37% of patients; 23% of ovarian cancer patients had a > or =50% reduction in CA125 levels. CONCLUSIONS: The maximum tolerated dose of this schedule was 130 mg/m(2). The toxicity profile at this dose was acceptable, with 7 of 28 patients treated developing grade 3/4 neutropenia and thrombocytopenia, 2 grade 4 diarrhea, and 2 grade 3/4 rash. This schedule was convenient and demonstrated activity in extensively pretreated patients; therefore, this is the recommended dose for study in Phase II trials.