Short-course olanzapine to prevent delayed emesis following carboplatin/paclitaxel for gynecologic cancer: a randomised study.

PURPOSE: To explore efficacy of short-course olanzapine with or without low-dose dexamethasone for prevention of delayed emesis in gynecologic cancer patients receiving carboplatin/paclitaxel. METHODS: This was a prospective study in 81 chemo-naive patients receiving 0.25 mg intravenous palonosetron, 16 mg dexamethasone, and 10 mg oral olanzapine before chemotherapy. On days 2 and 3, patients randomly received 10 mg olanzapine (arm A; n=27), 10 mg olanzapine plus 4 mg dexamethasone (arm B; n=27), or 8 mg dexamethasone (reference arm C; n=27). The primary endpoint was total control (TC; no vomiting, no rescue antiemetics, and no nausea) on days 2-5, using a diary. Secondary endpoints included proportion of patients with no emesis impact on daily life using the Functional Living Index-Emesis (FLIE) questionnaire, and patient's satisfaction with antiemetic coverage. RESULTS: Fifty-two percent of patients in arm A (P=0.406), 59% in arm B (P=0.779), and 67% in arm C had a delayed TC. Secondary analyses showed no significant difference across arms in any efficacy endpoint. FLIE scores as well as mean satisfaction scores were similar across arms. CONCLUSIONS: In this exploratory study with a small sample size, we did not find any clue about better control of delayed emesis with either olanzapine regimen in gynecologic cancer patients treated with carboplatin/paclitaxel and receiving the same prophylaxis for acute emesis.

A management system for randomized clinical trials: A novel way to supply medication.

BACKGROUND: Randomized controlled clinical trials require management effort, involving huge organizational, economic and informatics investments. Information technology offers opportunities to approach clinical trial methodology in new ways. However, there are only a few reports of computerized data and drug management systems. OBJECTIVE: This paper describes a novel software created specifically for the management of a randomized trial of diet and metformin in people with metabolic syndrome (the Me.Me.Me. trial). METHODS: Me.Me.Me. is an ongoing phase III randomized controlled trial in healthy people with metabolic syndrome to test the hypothesis that comprehensive lifestyle changes and/or metformin can prevent age-related chronic non-communicable diseases. To manage all the phases of the trial, we created a software which is a state pattern machine, user friendly, web-based, able to maintain the correct balance between randomization groups, and structured in various levels of security in order to guarantee the participant's privacy and compliance with the study protocol. The software achieves budget savings: drug management is not based on patients' packs, but on the actual need for drugs according to each participant's "state", with strict guidelines for the handling and supply of medication. RESULTS: The trial is ongoing and recruitment will close on August 31, 2018. To date, 11737 bottles of metformin/placebo have been dispensed to 1054 randomized participants, with drug savings of 29.5%. CONCLUSIONS: A software which takes into account the "state" of participant might be a powerful resource for developing and managing clinical trials, helping avoid poor treatment allocation, and wastage of drugs and money. ME.ME.ME. TRIAL: EUDRACT no. 2012-005427-32. ClinicalTrials.gov Identifier: NCT02960711.

A randomized controlled trial of Mediterranean diet and metformin to prevent age-related diseases in people with metabolic syndrome.

PURPOSE: Age-related non-communicable chronic diseases (ArCDs) are the leading cause of mortality. The major metabolic risk factor for their development is the metabolic syndrome (MetS), defined as a clustering of risk factors of metabolic origin such as abdominal obesity, high blood pressure, dyslipidemia and high fasting glycemia. There is increasing observational and experimental evidence that improving diet and the use of metformin (a calorie-restriction mimetic drug) may modify the risk of developing MetS and ArCD. We designed a phase III randomized controlled trial (the Me.Me.Me trial) to evaluate the effect of a comprehensive lifestyle intervention (including moderate physical activity and a Mediterranean-macrobiotic diet) and the effect of treatment with metformin in the prevention of ArCDs in healthy people with MetS. This report describes the scientific protocol of this trial. METHODS: The design of the study is 2 × 2 factorial with 2,000 volunteers to be randomized into 4 equal groups of 500 each, which are allocated to the following treatments: metformin (1,700 mg/day) + active lifestyle intervention, placebo + active lifestyle intervention, metformin (1,700 mg/day) alone, and placebo alone. The metformin/placebo component of the study is double blind. The study is planned for a term of 5 years. RESULTS: The Me.Me.Me. trial is ongoing and recruitment of participants is underway. No patient has completed the 5 years of follow-up. CONCLUSIONS: We believe that the results of the trial will clarify the importance of lifestyle for primary prevention and the role of metformin as a potential chemopreventive agent. The trial is registred on ClinicalTrials.gov with the identification NCT02960711.

Cost-utility and budget impact analyses of the use of NEPA for chemotherapy-induced nausea and vomiting prophylaxis in Italy.

OBJECTIVE: To evaluate the efficiency of resources allocation and sustainability of the use of netupitant+palonosetron (NEPA) for chemotherapy-induced nausea and vomiting (CINV) prophylaxis assuming the Italian National Health Service (NHS) perspective. A published Markov model was adapted to assess the incremental cost-utility ratio of NEPA compared with aprepitant (APR) + palonosetron (PALO), fosaprepitant (fAPR) + PALO, APR + ondansetron (ONDA), fAPR + ONDA in patients receiving a highly emetogenic chemotherapy (HEC) and with APR + PALO and fAPR + PALO in patients receiving a moderately emetogenic chemotherapy (MEC). SETTING: Oncology hospital department in Italy. METHODS: A Markov model was used to determine the impact of NEPA on the budget of the Italian NHS on a 5-day time horizon, corresponding to the acute and delayed CINV prophylaxis phases. Direct medical costs considered were related to antiemetic drugs, adverse events management, CINV episodes management. Clinical and quality of life data referred to previously published works. The budget impact analysis considered the aforementioned therapies plus PALO alone (for HEC and MEC) on a 5-year time horizon, comparing two scenarios: one considering the use of NEPA and one not considering its use. PRIMARY AND SECONDARY OUTCOME MEASURES: Incremental cost per quality adjusted life year (QALY) and differential economic impact for the Italian NHS between the two scenarios considered. RESULTS: NEPA is more effective and less expensive (dominant) compared with APR + PALO (for HEC and MEC), fAPR + PALO (for HEC and MEC), APR + ONDA (for HEC), fAPR + ONDA (for HEC). The use of NEPA would lead to a 5-year cost decrease of €63.7 million (€42.7 million for HEC and €20.9 million for MEC). CONCLUSIONS: NEPA allows an efficient allocation of resources for the Italian NHS and it is sustainable, leading to a cost decrease compared with a scenario which does not consider its use.

Cytotoxic extravasation: an issue disappearing or a problem without solution?

PURPOSE: The incidence and management of antitumoral compound extravasation that occurred in our medical day hospital unit were registered in a 10-year period. METHODS: A total of 114 episodes were consecutively recorded out of an estimated number of 211,948 administrations performed (0.05%). Type of compound, localization, timing, symptoms, treatment, resolution, or sequelae were documented. RESULTS: Extravasations after anthracyclines (17/114), platinum compounds (34/114), vinca alkaloids (7/114), and taxanes (34/114) were more frequently associated with edema and erythema ± pain. Five cases of monoclonal antibodies extravasation were observed without sequelae. With the involvement of an interdisciplinary task force and the use of dedicated guidelines, conservative management was successful in all patients. In the great majority of cases, recovery was complete within 48 hours after antidote administration. The support of our pharmacy was crucial. Physiatric evaluation was considered in several cases. No patients required surgery. CONCLUSIONS: We confirm that the adopted standardized approach to this event resulted in a satisfactory outcome and could be suggested as appropriate for managing extravasation in a large clinical context.

Prevention and treatment of oral mucositis in patients with head and neck cancer treated with (chemo) radiation: report of an Italian survey.

PURPOSE: There is a limited number of therapies with a high level of recommendations for mucositis, while several strategies are currently employed with a limited evidence for efficacy. A national survey among Italian oncologists who treat head and neck cancer (HNC) was conducted in order to assess the most common preventive and therapeutic protocols (including nutritional support and pain control) for oral mucositis (OM) in patients undergoing chemoradiotherapy. METHODS: From September to November 2012, a nationwide electronic survey with 21 focused items was proposed to chemotherapy and radiotherapy centers. RESULTS: We collected 111 answers. Common Terminology Criteria for Adverse Events (CTCAE) scale is employed by 55% of the physicians in assessing mucosal toxicity. The most relevant predictive factors for OM development are considered smoke, alcohol use, planned radiotherapy, and concurrent use of radiosensitizing chemotherapy. Prophylactic gastrostomy is adopted in <10% of the patients. Preventive antibiotics or antimycotics are prescribed by 46% of the responders (mainly local or systemic antimycotic drugs). Alkalinizing mouthwashes or coating agents are frequently adopted (70% of the cases). Among therapeutic interventions, systemic fluconazole is administered by 80% of the physicians. Pain is mainly treated by weak followed by strong opioids. CONCLUSIONS: A variety of preventive and therapeutic protocols for OM exists among the participating Italian centers, with some uniformity in respect to nutritional support, use of antimycotic and painkillers. There is an urgent need for well-conducted clinical trials aimed at assessing the best choices for OM prevention and treatment in HNC.