Effects of food-based interventions in the management of chemoradiotherapy-induced nausea and vomiting: a systematic review.

BACKGROUND: Cancer treatment-related nausea and vomiting continue to be common and distressing symptoms for patients, despite improvements in antiemetics. Dietary modifications could potentially improve this symptom experience. Clinicians frequently provide dietary advice to patients, although the evidence base of such suggestions or recommendations is not clear. PURPOSE: This systematic review aimed to examine the current literature on food interventions associated with improvements in cancer treatment-related nausea and vomiting. METHODS: Eight electronic databases were searched with a specific search term strategy covering trials without time or language limitations. Eligible studies focused on a food substance, defined as any nutritious substance that people eat or drink to maintain life and well-being. Trials in children and adults during chemotherapy or radiotherapy were included. Cochrane risk of bias tool was used to assess trial quality and GRADE was used to assess the certainty in the effect of each outcome. RESULTS: Seventeen trials were included, 3 focusing on children and 14 on adults. Two trials included patients receiving radiation. Ten out of 17 trials (59%) had a high risk of bias. Strongest evidence with highest certainty was found for dietary counseling to meet macronutrient requirements in reducing incidence of radiotherapy-related nausea and vomiting in adults (n=2 studies; n=124 participants; GRADE level: moderate). There was also moderate certainty in the beneficial effect of protein supplementation on nausea and vomiting incidence in adults during radiotherapy (n=2 studies; n=124 participants; GRADE level: moderate). A significant positive effect on CINV incidence and/or severity in adults was also found for dietary counseling to meet macronutrient requirements during chemotherapy, a peppermint drink, scaly wood mushroom, chamomile, protein with ginger, and a colorless odorless diet (GRADE level: low to very low). CONCLUSIONS: The review identified food-based approaches that could improve the nausea and vomiting experience in patients with cancer and provide guidance to clinicians. However, confidence in these findings was low and studies were heterogeneous and mostly of low quality, requiring further investigation before stronger recommendations can be made. Future research is needed to confirm efficacy and safety. TRIAL REGISTRATION: PROSPERO CRD42022341154.

Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial.

BACKGROUND: This multicentre, randomised, double-blinded, placebo-controlled, phase II/III trial aimed to evaluate an oral THC:CBD (tetrahydrocannabinol:cannabidiol) cannabis extract for prevention of refractory chemotherapy-induced nausea and vomiting (CINV). Here we report the phase II component results. PATIENTS AND METHODS: Eligible patients experienced CINV during moderate-to-high emetogenic intravenous chemotherapy despite guideline-consistent antiemetic prophylaxis. Study treatment consisted of one cycle of 1-4 self-titrated capsules of oral THC 2.5 mg/CBD 2.5 mg (TN-TC11M) three times daily, from days -1 to 5, and 1 cycle of matching placebo in a crossover design, then blinded patient preference for a third cycle. The primary end point was the proportion of participants with complete response during 0-120 h from chemotherapy. A total of 80 participants provided 80% power to detect a 20% absolute improvement with a two-sided P value of 0.1. RESULTS: A total of 81 participants were randomised; 72 completing two cycles were included in the efficacy analyses and 78 not withdrawing consent were included in safety analyses. Median age was 55 years (range 29-80 years); 78% were female. Complete response was improved with THC:CBD from 14% to 25% (relative risk 1.77, 90% confidence interval 1.12-2.79, P = 0.041), with similar effects on absence of emesis, use of rescue medications, absence of significant nausea, and summary scores for the Functional Living Index-Emesis (FLIE). Thirty-one percent experienced moderate or severe cannabinoid-related adverse events such as sedation, dizziness, or disorientation, but 83% of participants preferred cannabis to placebo. No serious adverse events were attributed to THC:CBD. CONCLUSION: The addition of oral THC:CBD to standard antiemetics was associated with less nausea and vomiting but additional side-effects. Most participants preferred THC:CBD to placebo. Based on these promising results, we plan to recruit an additional 170 participants to complete accrual for the definitive, phase III, parallel group analysis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616001036404; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370473&isReview=true.

Bowel cancer screening for women at midlife.

In Australia one in 15 women will be diagnosed with colorectal cancer in their lifetime because of the high incidences of lifestyle risk factors. The risk could be reduced by taking aspirin. Evidence-based Clinical Practice Guidelines for the prevention, early detection and management of colorectal cancer produced by Cancer Council Australia and approved by the National Health and Medical Research Council recommended that 'population screening in Australia, directed at those at average risk of colorectal cancer and without relevant symptoms, is immunochemical fecal occult blood testing every 2 years, starting at age 50 years and continuing to age 74 years.' Women at high risk because of family history will need more intense screening. At the current 40% participation rate, it is estimated that biennial screening with fecal immunohistochemical tests (FIT) reduces colorectal cancer incidence by 23% and mortality by 36%. The major adverse effects of screening are the psychological impact of a positive FIT that does not prove to be cancer, or adenomas on colonoscopy (47.7%), and the rare side-effects of colonoscopy of hemorrhage, bleeding or even death. A range of factors that could increase a woman's participation rate includes advice to screen from her general practitioner and more information about the nature of the screening tests.

e-TC: Development and pilot testing of a web-based intervention to reduce anxiety and depression in survivors of testicular cancer.

e-TC is an online intervention designed to address common psychosocial concerns of testicular cancer survivors. It aims to reduce anxiety, depression and fear of cancer recurrence by providing evidence-based information and psychological intervention. This paper details the development and pilot testing of e-TC. During pilot testing, 25 men (with varying psychological profiles) who had completed treatment for testicular cancer, 6 months to 5 years ago (which had not recurred), used e-TC over a 10-week period and provided quantitative and qualitative feedback on the feasibility and acceptability of the programme. Six men also completed a qualitative interview to provide detailed feedback on their experiences using e-TC. Fourteen men (56%) completed at least 80% of the programme. Participants reported a high level of satisfaction with the programme. Men's limited time was a barrier to programme use and completion, and participants suggested that men with a more recent diagnosis and a higher level of distress may be more likely to engage with the programme. e-TC appears to be a feasible and acceptable online intervention for survivors of testicular cancer. Findings from this study are currently being used to refine e-TC and guide the design of a larger efficacy study.

Cancer control-A global perspective.

Disparities in cancer control exist in low- and middle-income countries (LMICs). Many countries do not have cancer registries to record incidence, mortality and prevalence and are reliant on Globocan estimates of their cancer burden. Poorer cancer control within and between countries occurs in those living remotely from urban centres, those in a low socioeconomic group and some ethnic groups who have lifestyle and belief systems which impact on cancer control. High-income countries generally have population screening programmes for cervix, breast and bowel cancer. However, simpler forms of screening for cancer of the cervix like visual inspection with acetic acid have been shown to be feasible in developing nations. The widespread use of vaccines to prevent cancer has been achieved with the Hepatitis B vaccine but the human papilloma virus vaccine to prevent cancer of the cervix is largely only available in high-income countries. Access to and training of oncological surgeons in LMICs is limited, while 70% of patients in these countries cannot access radiotherapy. The World Health Organization has developed a list of essential medicines although access remains poor in LMICs. The United Nations has set targets for the control of non-communicable diseases to improve global cancer control.

The consumer-driven development and acceptability testing of a website designed to connect rural cancer patients and their families, carers and health professionals with appropriate information and psychosocial support.

Websites offer new opportunities to provide health-related information to rural communities. However, how acceptable they are to this population is unknown. This paper describes the consumer-led development of a website that provides rural-specific information on psychosocial care for rural South Australians affected by cancer, and examines its acceptability to users. The Country Cancer Support website was developed with people affected by cancer living in rural South Australia (N = 11), using a Participatory Action Research Framework and evidence-based behaviour change strategies. There were 32,389 visits in the first 3 years. An online survey (N = 111) revealed that users found the website easy to use, helpful and relevant. Most rural cancer patients and supporters (98.11%) believed it had been written by people who understood what they were going through. Patients and supporters for whom it was relevant, reported feeling more motivated and confident in accessing psychosocial support services in their rural area (66.67%) and/or capital city (67.65%) and/or in travelling for medical treatment (75.86%). Many also felt less isolated (73.33%) and/or distressed (53.57%). All health professionals reported gaining new knowledge. This study shows that carefully designed websites can successfully address rural populations' health information needs and increase intentions to access psychosocial support.

Wiki-based clinical practice guidelines for the management of adult onset sarcoma: a new paradigm in sarcoma evidence.

In 2013 Australia introduced Wiki-based Clinical Practice Guidelines for the Management of Adult Onset Sarcoma. These guidelines utilized a customized MediaWiki software application for guideline development and are the first evidence-based guidelines for clinical management of sarcoma. This paper presents our experience with developing and implementing web-based interactive guidelines and reviews some of the challenges and lessons from adopting an evidence-based (rather than consensus-based) approach to clinical sarcoma guidelines. Digital guidelines can be easily updated with new evidence, continuously reviewed and widely disseminated. They provide an accessible method of enabling clinicians and consumers to access evidence-based clinical practice recommendations and, as evidenced by over 2000 views in the first four months after release, with 49% of those visits being from countries outside of Australia. The lessons learned have relevance to other rare cancers in addition to the international sarcoma community.

Testosterone deficiency and quality of life in Australasian testicular cancer survivors: a prospective cohort study.

This is the first prospective study in a contemporary Australian/New Zealand population to determine the prevalence of testosterone deficiency in testicular cancer survivors at 12 months from treatment, and any association with poorer quality of life. Hormone assays from 54 evaluable patients in a prospective cohort study revealed biochemical hypogonadism in 18 patients (33%) and low-normal testosterone in 13 patients (24%). We found no association between testosterone levels and quality of life (all P > 0.05). Hypogonadal patients should be considered for testosterone replacement to prevent long-term morbidity.

Results of a 7-day aprepitant schedule for the prevention of nausea and vomiting in 5-day cisplatin-based germ cell tumor chemotherapy.

PURPOSE: The purpose of this study was to determine the efficacy of adding a 7-day aprepitant schedule to a 5HT3 receptor antagonist and dexamethasone for patients with germ cell tumors receiving first-line 5-day cisplatin-based chemotherapy. METHODS: In a single-arm, open-label, multi-center, phase 2 trial, chemo-naive patients received aprepitant 125 mg PO (per oral) on day 1 and 80 mg PO on days 2 to 7, a 5HT3 receptor antagonist on days 1 to 5, and dexamethasone 8 mg on days 1 to 8. The primary endpoint was no emesis (vomiting or dry retching) during days 1 to 7 of cycle 1. RESULTS: Fifty patients were recruited. For cycle 1, proportions reporting no emesis on day 1, no emesis on days 1 to 7, no nausea on day 1, and no nausea on days 1 to 7 were 96, 82, 71, and 27%, respectively. The efficacy was maintained in all cycles with over 80% of patients reporting no emesis on any given day of any given cycle. Emesis was more common on days 4 to 7 (68% episodes) than on days 1 to 3 (32% episodes). Over any 24-h period, 49% of patients with emesis reported no more than two episodes, and 62% of patients with nausea reported intensity as 3 or less on a scale from 0 to 10. There were no unexpected or serious adverse events reported. CONCLUSION: Adding 7 days of aprepitant to a 5HT3 receptor antagonist and dexamethasone effectively controlled acute and delayed emesis with 5-day cisplatin regimens. Days of nausea were more common than days of vomiting.

Prevalence and predictors of complementary and alternative medicine (CAM) use by men in Australian cancer outpatient services.

BACKGROUND: Although studies have shown that complementary and alternative medicine (CAM) use is common in cancer patients, no survey has assessed CAM use in men with a variety of cancers. In Australia, no data exist about male cancer patients' use of CAM. PATIENTS AND METHODS: A self-administered questionnaire was completed by 403 men attending four cancer outpatient services in Metropolitan Adelaide. Data were analyzed using Pearson's χ(2) tests and multivariate logistic regression analysis. RESULTS: CAMs were currently used by 52.9%, or used at some point by 61.5%, of respondents. The most popular CAM treatments were dietary supplements (36.1%), prayer (25.9%), herbs and botanicals (21.4%), and relaxation techniques/meditation (15.2%). CAM use was directed by a cancer specialist in 9.9% of respondents. Independent predictors of CAM use were metastatic cancer (P = 0.022), actively practicing religion (P = 0.008), and tertiary education (P = 0.007). CONCLUSIONS: CAM use in males is equally common across all cancer diagnoses, namely prostate, hematological malignancies, colorectal, lung, and other cancers. Oncologists should be aware that one-third of male patients modify their diet and/or search for spiritual guidance, particularly when diagnosed with metastatic cancer.

Improving cancer treatment by addressing legislative and regulatory issues.

OBJECTIVES: To explore legislative and legal barriers to improving cancer treatment. METHODS: The advocacy agenda of Cancer Council Australia was examined for key issues, and examples drawn from Australian law were presented at a conference entitled 'Legislate, regulate and litigate: legal perspectives on cancer prevention and treatment' at the University of Sydney. RESULTS: The introduction of electronic medical records and linkage of data sets from registries can produce very useful public health information, but could be a threat to individual privacy. The balance between these must underpin legislation and regulation. The new drug approval process must keep pace with developments such as targeted therapies, where tests to identify the presence of the target must also be approved simultaneously. The regulation of complementary and alternative medicines in cancer is challenging given their widespread use. In cancer research, it is vital that the important ethics and governance review process does not become a barrier to the ability to complete research in a reasonable time frame. A specific issue for future treatments and diagnostic tests that are to be targeted at genes and their products is to clarify gene patenting laws so that invention is rewarded, not mere discovery. The nature of the workforce will need to change to meet the treatment needs of an increasing incidence of cancer in an aging population, but regulation will need to ensure the maintenance of safety and quality standards. CONCLUSION: The flexibility of legislation and regulation to meet a rapidly changing environment is key to ensuring the timely adoption of new cancer treatments to improve cancer outcomes.

Are guidelines on use of colony-stimulating factors in solid cancers flawed?

In cancer care in Australia, we are very reliant on an array of expensive pharmaceuticals. Our use of these treatments is often based on multinational or foreign clinical studies. Oncologists are, to varying degrees, reliant on how the studies are interpreted by the writers of journal editorials, clinical guidelines and opinion pieces. Therefore it is important that these guidelines are balanced and evidence based. We have examined in detail one of the most influential and wide ranging clinical guidelines used in oncology, The American Society of Clinical Oncology (ASCO) 2006 Update of Recommendations for the use of White Blood Cell Factors: An Evidence-Based Clinical Practice Guideline. We have discussed in detail some of the controversial recommendations in this guideline and have exposed what we believe are some flaws in these recommendations. We would urge that we continue to be rigorous in our oversight of international research agendas and international clinical guidelines in the future.

A phase II trial of lomeguatrib and temozolomide in metastatic colorectal cancer.

To evaluate the tumour response to lomeguatrib and temozolomide (TMZ) administered for 5 consecutive days every 4 weeks in patients with metastatic colorectal carcinoma. Patients with stage IV metastatic colorectal carcinoma received lomeguatrib (40 mg) and TMZ (50-200 mg m(-2)) orally for 5 consecutive days every 4 weeks. Response was determined every two cycles. Pharmacokinetics of lomeguatrib and TMZ as well as their pharmacodynamic effects in peripheral blood mononuclear cells (PBMC) were determined. Nineteen patients received 49 cycles of treatments. Despite consistent depletion of O(6)-methylguanine-DNA methyltransferase in PBMC, none of the patients responded to treatment. Three patients had stable disease, one for the duration of the study, and no fall in carcinoembryonic antigen was observed in any patient. Median time to progression was 50 days. The commonest adverse effects were gastrointestinal and haematological and these were comparable to those of TMZ when given alone. This combination of lomeguatrib and TMZ is not efficacious in metastatic colorectal cancer. If further studies are to be performed, emerging data suggest that higher daily doses of lomeguatrib and a dosing period beyond that of TMZ should be evaluated.

Phase II study of IV vinflunine in patients with chemotherapy naive metastatic malignant melanoma.

This phase II study evaluated vinflunine in chemotherapy naive patients with metastatic melanoma. Vinflunine was administered at 350 mg/m(2) every 3 weeks, but after 9 patients this was reduced to 320 mg/m(2) based on interim analyses of all phase II trials. A partial response was observed in 1 of the first 9 patients (11.1%) treated at 350 mg/m(2), which gives a 3.0% [95% confidence interval (CI): 0.08-15.8] response rate in 33 patients. No change was the best response in 13 patients (39.4%) with progressive disease in 16 (48.5%) and 3 were not evaluable for response. The time to response was 1.4 months and duration was 6 months. At 350 mg/m(2) grade 4 neutropaenia occurred in 3 patients (33.3%) and grade 3 in 2 patients (22.2%) while at 320 mg/m(2) grade 4 neutropaenia occurred in 6 patients (25%) and grade 3 in 3 patients (12.5%) with 2 episodes of grade 3 febrile neutropaenia. Two patients (8.3%) had grade 3 anaemia. These results do not show activity at this dose and schedule for vinflunine in patients with chemotherapy naive metastatic melanoma.

Why we will need to learn new skills to control cancer.

As a society and as specialists involved in the diagnosis and management of cancer, we must begin to find new cost-effective ways to provide equitable access to the innovative, effective and expensive drugs that may begin to make cancer a chronic rather than rapidly lethal disease. Drugs such as trastuzumab and gefitinib are safer 'targeted therapies' that only attract government subsidies after the pathologist identifies the target present in a minor subset of patients. Nonetheless, funding for pathological identification of these targets remains a challenge. To illustrate, gefitinib may produce 'Lazarus' responses and prolonged survival among patients with epidermal growth factor receptor mutation-positive non-small-cell lung cancer. Many such examples will enter the clinical domain in the coming years. As we enter this era of personalized medicine, we argue that the use of expensive targeted therapies should be limited to pathologically proven indications because truly effective drugs are best applied to those individuals who would most benefit. It follows that medical oncologists should be trained properly to use targeted therapies. Then a new generation of oncologists would be empowered to participate in the iterative cycles of research between bench and bedside that are necessary for optimal use of biotherapies and their integration into multimodality cancer treatment programmes. We propose that cancer pathology be made available as a training option in the postgraduate education of medical oncologists. Oncologists and pathologists may jointly administer and mutually accredit the training module, which may also contribute towards the award of a higher degree.

Feasibility study on the MammoSite in early-stage breast cancer: initial experience.

The aims of this study were to evaluate the feasibility, practicality, efficacy and safety of the delivery of accelerated partial breast irradiation using the MammoSite for the boost phase. Six patients aged 53-69 years with stage T1N0, T2N0, Grade I-II invasive ductal carcinoma received 9-10 Gy prescribed at 1 cm from the MammoSite balloon surface in two fractions of 4.5-5 Gy 6 h apart. The MammoSite was inserted 20-37 days postoperatively. External beam radiation therapy to the whole breast commenced 1-5 days after accelerated partial breast irradiation. The maximum skin dose ranged from 3 to 9 Gy. The skin-cavity distance ranged from 7 to 19 mm. Local discomfort resolved as the scar healed spontaneously within 3-5 days. No Grade III or higher acute toxicity or local infection was recorded. The ease of insertion and accuracy of dosimetry makes the MammoSite suitable for use in properly selected women with early-stage breast cancer in a trial setting.

Gemcitabine and carboplatin in carcinoma of unknown primary site: a phase 2 Adelaide Cancer Trials and Education Collaborative study.

Cancer of unknown primary site (CUP) represents up to 5% of all cancer diagnoses and is associated with poor survival. We have performed a prospective multicentre phase 2 trial to evaluate efficacy and toxicity of the combination of gemcitabine (G) and carboplatin (C) for patients with CUP. Patients with histologically confirmed metastatic carcinoma in which the primary site of cancer was not evident after prospectively designated investigation and who had ECOG performance status 0-2 were treated with G 1000 mg m(-2) intravenously (i.v.) days 1 and 8, and C AUC 5 i.v. on day 8 every 3 weeks to a maximum of nine cycles. The primary end points were response rate, and toxicity, with secondary end points of progression-free survival and overall survival. Fifty-one (23 male, 27 female) patients were enrolled (one patient ineligible), with a median age of 69 years (range 41-83 years). Fifty patients were evaluable for toxicity and 46 patients were evaluable for efficacy. The overall response rate to the GC regimen was 30.5%. With a median follow-up of 24 months, the median progression-free survival was 18 weeks (4.2 months) and the median overall survival was 34 weeks (7.8 months). The frequency of grade 3 or 4 toxicity was low. Nausea/vomiting was the most common side effect, but was usually only mild in severity. Uncomplicated neutropenia (14%), thrombocytopenia (10%) and anaemia (8%) were the most common causes of grade 3-4 toxicity. The regimen was very well tolerated, particularly in the elderly. The GC regimen is an active regimen in CUP with excellent tolerability and should be considered particularly for elderly patients with CUP.