SMILE Study Research Articles

Effectiveness and Safety of IPN-20-SENSE LIDOCAINE for Lip Volume Augmentation and/or Redefinition (SMILE Study): A Non-inferiority Randomized Double-Blinded Controlled Study.

Hyaluronic acid (HA) is a widely used dermal filler for lip augmentation. IPN-20-SENSE LIDOCAINE (Laboratoires VIVACY) is a monophasic gel consisting of cross-linked HA and includes lidocaine hydrochloride for the reduction of injection-associated pain. The SMILE study was designed to assess the non-inferiority of IPN-20-SENSE LIDOCAINE compared to HA-RK-Lido in improving aesthetic lip appearance. The secondary objectives were to evaluate the effectiveness and safety of IPN-20-SENSE LIDOCAINE against the chosen similar active control device. This was a prospective, multicenter, double-blinded, randomized active controlled parallel group study undertaken in two investigational sites between May 2021 and July 2022 (14 months). The primary endpoint of this study was the proportion of subjects reporting an improvement on the Global Aesthetic Improvement Scale (GAIS) 3 months after treatment initiation. Regarding the primary endpoint, the difference between the treatment arms in the proportion of improved subjects was +7.0[-2.2;17.7]. The lower limit of this 90%CI, being above the non-inferiority margin of -15 and below zero, demonstrated the non-inferiority of IPN-20-SENSE LIDOCAINE vs. HA-RK-Lido. The secondary outcomes reported by subjects and the blinded live evaluators supported this result. All injection site reactions and device-related adverse events reported in this study were expected, already described and were mostly mild and transient. The study demonstrated the non-inferiority of IPN-20-SENSE LIDOCAINE to HA-RK-Lido in the aesthetic improvement of the lips. The effect of both treatments decreased over time. Nonetheless, aesthetic improvement was sustained longer in the IPN-20-SENSE LIDOCAINE arm. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

TCT-227 Timing and Indications for Cangrelor Use and Transition Modalities to Oral P2Y12 Inhibitors in Patients Undergoing PCI: Insights From the SMILE Study

TCT-227 Timing and Indications for Cangrelor Use and Transition Modalities to Oral P2Y12 Inhibitors in Patients Undergoing PCI: Insights From the SMILE Study

P2.09-29 Efficacy of Osimertinib (OSI) vs 1st-Generation TKI Followed by OSI by Clinical Profile in EGFR-Mutant NSCLC (SMILE STUDY)

P2.09-29 Efficacy of Osimertinib (OSI) vs 1st-Generation TKI Followed by OSI by Clinical Profile in EGFR-Mutant NSCLC (SMILE STUDY)

Abstract OT2-01-02: The SMILE Study: A phase II trial of onapristone in combination with fulvestrant for patients with ER-positive and HER2-negative metastatic breast cancer after progression on endocrine therapy and CDK 4/6 inhibitors

Abstract Background Antiprogestins, including selective progesterone receptor (PgR) modulators (SPRMs) that act as PgR antagonists, are a promising class of therapeutics for overcoming endocrine resistance including in patients who develop activating estrogen receptor alpha (ESR1) mutations after prior endocrine therapy (ET). The SMILE study is a multi-institutional phase II clinical trial to determine the efficacy and safety of an antiprogestin, onapristone in combination with fulvestrant as second-line therapy for patients with ER+,PgR+/-, HER2 -metastatic breast cancer (MBC). Methods Patients with locally advanced or MBC who progress on ≥2 lines of prior therapy with ET as a single agent or in combination with CDK4/6 inhibitors, mTOR inhibitors and one line of chemotherapy in the metastatic setting are eligible. Other criteria include ECOG performance status ≤ 2, measurable disease per RECIST 1.1 criteria, adequate organ function, availability of an archived tumor biopsy block confirming the diagnosis of MBC, optional biopsy at disease progression on trial, and optional 18F-fluorofuranylnorprogesterone (18F-FFNP) PET/CT imaging. Ovarian suppression is allowed. Prior ET with tamoxifen or aromatase inhibitor therapy in the adjuvant or metastatic setting is allowed. Patients with prior exposure to fulvestrant, antiprogestins, or CDK inhibitors in the adjuvant setting are ineligible. Following consent, all subjects will receive fulvestrant at the recommended dosing schedule plus onapristone 50 mg orally, twice daily, until disease progression, unacceptable toxicity, or discontinuation for any other reason. Using the Simon Two-Stage design, a total of 39 patients will be enrolled over two years from 6-8 sites within Wisconsin Oncology Network (WON); study enrollment began in November 2021. In the first stage of the trial, thus far, nine patients were accrued who are tolerating the trial regimen well with no reported toxicities or serious events. The safety monitoring is planned when the cohort size reaches eleven patients, and interim analysis at 21 patients; if ≥2 responses are observed, then 18 additional subjects will be enrolled in the second stage. This design yields a one-sided type I error rate of 5% if the ORR is 7% and power of 80% when the combination’s true response rate is 20%. The primary objective is to evaluate the objective response rate; secondary objectives include safety and tolerability, progression-free survival, disease control rate, and duration of response. Other correlates include optional functional imaging of PgR binding with 18F-FFNP PET/CT and biomarker analysis (ER, total PgR, HER2, Ki67, CD24, CD44, LDH1, KLF4, CK 5/6, PhosphoSer294-PgR on tissue samples, ESR1 mutations, and circulating tumor DNA analysis). Citation Format: Sailaja Kamaraju, Amy Fowler, Lubna N. Chaudhary, Mark Burkard, Thomas Giever, Robert N Hegeman, Michele Pipp-Dahm, Yee Chung Cheng, Carol Lange, Julie M. Jorns, Amy Stella, Nauman Siddiqui, Luke Zurbriggen, Saurabh Rajguru, Sergey Tarima, Deepika Sriram, Janet Retseck, Hallgeir Rui, Tarek Sahmoud, Kari B. Wisinski. The SMILE Study: A phase II trial of onapristone in combination with fulvestrant for patients with ER-positive and HER2-negative metastatic breast cancer after progression on endocrine therapy and CDK 4/6 inhibitors [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-01-02.

Prevention and treatment of psychiatric disorders through physical activity, exercise, and sport

Prevention and treatment of psychiatric disorders through physical activity, exercise, and sport

Abstract OT2-16-01: The SMILE study: A phase 2 trial of onapristone in combination with fulvestrant for patients with ER+ and HER2- metastatic breast cancer after progression on endocrine therapy and CDK4/6 inhibitors

Abstract Background Antiprogestins, including selective progesterone receptor (PgR) modulators (SPRMs) that act as PgR antagonists, are a promising class of therapeutics for overcoming endocrine resistance including in patients who develop activating estrogen receptor 1 (ESR1) mutations after prior endocrine therapy (ET). The SMILE study (NCT04738292) is a multi-institutional phase II clinical trial to determine the efficacy and safety of an antiprogestin, onapristone in combination with fulvestrant as second-line therapy for patients with ER+,PgR+, HER2 -metastatic breast cancer (MBC). Methods Patients with locally advanced or MBC who progress on ≥2 lines of prior therapy with ET as a single agent or in combination with CDK4/6 inhibitors, mTOR inhibitors and one line of chemotherapy in the metastatic setting are eligible. Other criteria include ECOG performance status ≤ 2, measurable disease per RECIST 1.1 criteria, adequate organ function, availability of an archived tumor biopsy block confirming the diagnosis of MBC, optional biopsy at disease progression on trial, and optional 18F-fluorofuranylnorprogesterone (18F-FFNP) PET/CT imaging. Ovarian suppression is allowed. Prior ET with tamoxifen or aromatase inhibitor therapy in the adjuvant or metastatic setting is allowed. Patients with prior exposure to fulvestrant, antiprogestins, or CDK inhibitors in the adjuvant setting are ineligible. Following consent, all subjects will receive fulvestrant at the recommended dosing schedule plus onapristone 50 mg orally, twice daily, until disease progression, unacceptable toxicity, or discontinuation for any other reason. Using the Simon Two-Stage design, a total of 39 patients will be enrolled over two years from 6-8 sites within Wisconsin Oncology Network (WON). In the first stage of the trial, 21 subjects will be enrolled; if ≥2 responses are observed, then 18 additional subjects will be enrolled in the second stage. This design yields a one-sided type I error rate of 5% if the ORR is 7% and power of 80% when the combination's true response rate is 20%. The primary objective is to evaluate the objective response rate; secondary objectives include safety and tolerability, progression-free survival, disease control rate, and duration of response. Other correlates include optional functional imaging of PgR binding with 18F-FFNP PET/CT and biomarker analysis (ER, total PgR, HER2, Ki67, CD24, CD44, LDH1, KLF4, CK 5/6, PhosphoSer294-PgR on tissue samples, ESR1 mutations, and circulating tumor DNA analysis). The study was approved in January 2021, and enrollment is active at the time of this submission. Citation Format: Sailaja Kamaraju, Amy Fowler, Chung Yee Cheng, Lubna N Chaudhary, John Burfeind, Janet Retseck, Amye J Tevaarwerk, Mark Burkard, Elisavet Paplomata, Amanda M Parkes, Julie M Jorns, Sergey Tarima, Douglas Yee, Hallgeir Rui, Carol Lange, Tarek Sahmoud, Kari B Wisinski. The SMILE study: A phase 2 trial of onapristone in combination with fulvestrant for patients with ER+ and HER2- metastatic breast cancer after progression on endocrine therapy and CDK4/6 inhibitors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-16-01.

Exploring Stem Cell Transplanted Patients' Perspectives on Medication Self-Management and Electronic Monitoring Devices Measuring Medication Adherence: A Qualitative Sub-Study of the Swiss SMILe Implementation Science Project.

PurposeLittle is known about allogeneic stem cell transplant (alloSCT) patients’ medication adherence strategies. Acceptability and preferences regarding electronic monitoring (EM) systems to assess all three phases of medication adherence (ie, initiation, implementation, persistence) are crucial to allow their successful implementation in clinical or research settings but have not yet been evaluated. We therefore aimed to explore: 1) alloSCT patients’ medication adherence and self-management strategies; and 2) their acceptability and preferences of three different EM systems (MEMS Cap, Helping Hand, Button) as part of the Swiss SMILe study.Patients and MethodsRespecting anti-pandemic measures, we used a purposive sample of six adult alloSCT patients from the University Hospital Basel, Switzerland (USB)—6 weeks to 2 years post-alloSCT—to conduct three focus group sessions with two patients each. Using a semi-structured outline, we explored 1) patients’ medication adherence strategies and medication self-management; and 2) their acceptance and preferences regarding EM use. The three tested EM systems were available for testing during each session. Discussions were audio-recorded, visualized using mind-mapping and analyzed using Mayring’s qualitative content analysis.ResultsPatients (33% females; mean age 54.6±16.3 years; 10.4±8.4 months post-alloSCT) used medication adherence enhancing strategies (eg, preparing pillbox, linking intake to a habit). Still, they indicated that post-alloSCT medication management was challenging (eg, frequent schedule changes). All participants preferred the MEMS Button. Participants said its small size and the possibility to combine it with existing pillboxes (eg, putting it into/next to them) made them more confident about implementing it in their daily lives.ConclusionRegarding EM systems for medication adherence, end-user preferences and acceptability influence adoption and fidelity. Of the three systems tested, our sample found the MEMS Button most acceptable and most preferable. Therefore, we will use it for our USB SMILe study.

Implementation Science Meets Software Development to Create eHealth Components for an Integrated Care Model for Allogeneic Stem Cell Transplantation Facilitated by eHealth: The SMILe Study as an Example.

To describe a process of creating eHealth components for an integrated care model using an agile software development approach, user-centered design and, via the Behavior Change Wheel, behavior theory-guided content development. Following the principles of implementation science and using the SMILe project (integrated care model for allogeneic stem cell transplantation facilitated by eHealth) as an example, this study demonstrates how to narrow the research-to-practice gap often encountered in eHealth projects. We followed a four-step process: (a) formation of an interdisciplinary team; (b) a contextual analysis to drive the development process via behavioral theory; (c) transfer of content to software following agile software development principles; and (d) frequent stakeholder and end user involvement following user-centered design principles. Our newly developed comprehensive development approach allowed us to create a running eHealth component and embed it in an integrated care model. An interdisciplinary team's collaboration at specified interaction points supported clear, timely communication and interactions between the specialists. Because behavioral theory drove the content development process, we formulated user stories to define the software features, which were prioritized and iteratively developed using agile software development principles. A prototype intervention module has now been developed and received high ratings on the System Usability Scale after two rounds of usability testing. Following an agile software development process, structured collaboration between nursing scientists and software specialists allowed our interdisciplinary team to develop meaningful, theory-based eHealth components adapted to context-specific needs. The creation of high-quality, accurately fitting eHealth components specifically to be embedded in integrated care models should increase the chances of uptake, adoption, and sustainable implementation in clinical practice.

An Observational Study of Team Management Approach for CapeOX Therapy in Patients with Advanced and Recurrent Colorectal Cancer: SMILE Study (The Study of Metastatic colorectal cancer to investigate the Impact of Learning Effect).

Objectives: In recent years, CapeOX therapy for patients with colorectal cancer is widely used. We previously reported that a multidisciplinary approach decreases the worsening of adverse events and increases patient satisfaction. In this study, we conducted a multicenter, prospective, observational study to evaluate the incidence of adverse events, health-related quality of life (HRQOL) of the patient, and efficacy of a management (intervention) according to the support system (SMILE study). Methods: As the interventional method, the following more than one method was carried out in each institute, 1: support with telephone, 2: dosing instruction by a pharmacist, 3: skin care instruction by a nurse, and 4: patient instruction by a doctor. The primary endpoint was the incidence of hand-foot syndrome (HFS) of more than grade 2. The secondary endpoint was the HRQOL evaluation and efficacy. The questionnaire (HADS) was administered before the start of the chemotherapy and in 1, 2, 4, 5, and 8 courses to evaluate quality of life (QOL). Results: From April 2011 to September 2012, 80 patients were enrolled from 14 sites, and all patients were the subjects of analysis. The demographic background was as follows: man/woman: 46/34, age median: 63 (36-75), and management interventional method 1/2/3/4: 36/68/73/78. The overall percentage of HFS that exceeded grade 2 within 6 months was 16.3%. It was 11.1% with the telephone support group and 20.5% without the telephone support group (p = 0.26). Conclusions: A multi-professional telephone support may reduce the deterioration of HFS. Further study which includes larger cohort is needed in the future.

In high-risk type 1 diabetes, insulin pumps with suspend-before-low technology reduced hypoglycemic events.

Source Citation Bosi E, Choudhary P, de Valk HW, et al; SMILE Study Group. Efficacy and safety of suspend-before-low insulin pump technology in hypoglycaemia-prone adults with type 1 diabetes (SMILE): an open-label randomised controlled trial. Lancet Diabetes Endocrinol. 2019;7:462-72. 31047902

Factors associated with improvement in symptoms and quality of life for first-line EGFR-tyrosine kinase inhibitor treatment in patients with EGFR-mutated non-small-cell lung cancer - A multicenter prospective SMILE study

Introduction: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a standard first-line treatment for advanced EGFR-mutated NSCLC patients. Factors associated with symptoms and quality of life (QOL) improvements have not been investigated.Methods: We conducted a multicenter, prospective study to evaluate improvements in QOL and symptoms in NSCLC patients treated with first-line EGFR-TKIs. QOL was assessed using the instrument of Functional Assessment of Cancer Therapy-Lung questionnaire (FACT-L) and Treatment Outcome Index (TOI). Assessment of symptoms was evaluated using the Lung cancer subscale (LCS).Results: Eligible subjects included 280 patients for endpoint analyses. The mean FACT-L score increased by 4.0 ± 15.56 at Week 2 (p<0.001), 5.1 ± 18.48 at Week 4 (p<0.001), and 4.2 ± 20.27 at Week 12 (p=0.001). Similarly, a 2.3 ± 11.65 (p<0.001), 3.2 ± 13.59 (p<0.001), and 2.4 ± 14.34 (p=0.009) increase in mean TOI score were observed at Weeks 2, 4 and 12, respectively. For LCS, it was slightly increased by 1.7 ± 4.61, 2.0 ± 5.50, and 2.0 ± 5.36 at Weeks 2, 4, and 12 (all p<0.001), respectively. Subgroup analyses showed patients who were ex-smokers or with at least 3 metastatic sites were associated with symptoms improvement. Patients who were ex-smokers, with at least 3 metastatic sites, a PS of 1, or treated with gefitinib were associated with QOL improvement.Conclusions: In EGFR -mutated NSCLC patients who were treated with first-line EGFR-TKIs, these ex-smokers or with 3 or more metastatic sites were associated with improvements in symptoms and QOL.

Do general practitioners record alcohol abuse in the electronic medical records? A comparison of survey and medical record data

Objective: Primary care professionals are encouraged to screen patients for alcohol abuse. However, patients with alcohol abuse are often under-diagnosed as well as under-registered in medical records in general practices. This study aims to report on the registration rates of alcohol abuse diagnoses in general practices in comparison to patients’ self-reported rates of alcohol use disorder.Research design and methods: Data of a total number of 2,349 patients were analyzed from the SMILE study, a large prospective cohort study conducted in The Netherlands. Two data collection strategies were combined: (1) Patient self-report data on alcohol consumption as well as other sociodemographic characteristics; (2) Medical record (ICPC codes) data of diagnoses of chronic and acute alcohol abuse of the same patients. GPs’ registrations of diagnoses were compared with the self-report data using descriptive statistics.Results: Based on the results of the patient reported data, 179 (14.8%) male participants had an alcohol use disorder. Of the total number of female patients, 82 (7.2%) had an alcohol use disorder. One of the male and none of the female patients with an alcohol use disorder were registered as such by the GP.Conclusions: This study found that 11.1% of the total patient sample reported an alcohol use disorder, of which a strikingly low number of patients were recorded as such by their GP. It is likely that low recognition due to barriers related to alcohol screening as well as registration avoidance due to the stigma around alcohol abuse play a role in low registration.

P3.01-016 Factors Associated with Symptoms Improvement and HRQoL for First-Line EGFR-TKIs in NSCLC: A Multicenter Prospective SMILE Study

First-line epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) offer an advantage compared to doublet chemotherapy in progression free survival, tolerability, and quality of life (QOL) in EGFR-mutated advanced non-small cell lung cancer (NSCLC) patients. In Taiwan, gefitinib, erlotinib and afatinib are all reimbursed as first-line therapy. It provides a rare opportunity to investigate factors associated with the extent of symptoms and QOL improvement in real-world patient population.

A comparison of the responsiveness of EQ-5D-5L and the QOLIE-31P and mapping of QOLIE-31P to EQ-5D-5L in epilepsy

ObjectiveTo investigate the responsiveness of and correlation between the EQ-5D-5L and the QOLIE-31P in patients with epilepsy, and develop a mapping function to predict EQ-5D-5L values based on the QOLIE-31P for use in economic evaluations.MethodsThe dataset was derived from two clinical trials, the ZMILE study in the Netherlands and the SMILE study in the UK. In both studies, patients’ quality of life using the EQ-5D-5L and QOLIE-31P was measured at baseline and 12 months follow-up. Spearman’s correlations, effect sizes (EF) and standardized response means (SRM) were calculated for both the EQ-5D-5L and QOLIE-31P domains and sub scores. Mapping functions were derived using ordinary least square (OLS) and censored least absolute deviations models.ResultsA total of 509 patients were included in this study. Low to moderately strong significant correlations were found between both instruments. The EQ-5D-5L showed high ceiling effects and small EFs and SRMs, whereas the QOLIE-31P did not show ceiling effects and also showed small to moderate EFs and SRMs. Results of the different mapping functions indicate that the highest adjusted R2 we were able to regress was 0.265 using an OLS model with squared terms, leading to a mean absolute error of 0.103.ConclusionsResults presented in this study emphasize the shortcomings of the EQ-5D-5L in epilepsy and the importance of the development of condition-specific preference-based instruments which can be used within the QALY framework. In addition, the usefulness of the constructed mapping function in economic evaluations is questionable.

Implementation fidelity of a self-management course for epilepsy: method and assessment

BackgroundComplex interventions such as self-management courses are difficult to evaluate due to the many interacting components. The way complex interventions are delivered can influence the effect they have for patients, and can impact the interpretation of outcomes of clinical trials. Implementation fidelity evaluates whether complex interventions are delivered according to protocol. Such assessments have been used for one-to-one psychological interventions; however, the science is still developing for group interventions.MethodsWe developed and tested an instrument to measure implementation fidelity of a two-day self-management course for people with epilepsy, SMILE(UK). Using audio recordings, we looked at adherence and competence of course facilitators. Adherence was assessed by checklists. Competence was measured by scoring group interaction, an overall impression score and facilitator “didacticism”. To measure “didacticism”, we developed a novel way to calculate facilitator speech using computer software. Using this new instrument, implementation fidelity of SMILE(UK) was assessed on three modules of the course, for 28% of all courses delivered.ResultsUsing the instrument for adherence, scores from two independent raters showed substantial agreement with weighted Kappa of 0.67 and high percent agreement of 81.2%. For didacticism, the results from both raters were highly correlated with an intraclass coefficient of 0.97 (p < 0.0001). We found that the courses were delivered with a good level of adherence (> 50% of scored items received the maximum of 2 points) and high competence. Groups were interactive (mean score: 1.9–2.0 out of 2) and the overall impression was on average assessed as “good”. Didacticism varied from 42% to 93% of total module time and was not associated with the other competence scores.ConclusionThe instrument devised to measure implementation fidelity was reproducible and easy to use. The courses for the SMILE(UK) study were delivered with a good level of adherence to protocol while not compromising facilitator competence.Trial registrationISRCTN57937389.

Who Needs Longer Tolvaptan Treatment?

The vasopressin receptor 2 (V2) receptor antagonist tolvaptan is an aquaretic agent that has been approved for heart failure patients with volume overload in Japan. In this study (SMILE study), we investigated patient characteristics and effectiveness in both a 14 days and shorter treated group (14DS) and 15 days and longer treated group (15DL). The results showed that the patients in the 15DL group had low cardiac output with intensive diuretic administration (ie, diuretic resistance). The congestive symptoms were greatly improved within 14 days of treatment in both the 14DS and 15DL groups. Further improvements in lower limb edema, pulmonary congestion, dyspnea, third sound, and rales after 2 weeks were statistically significant in the 15DL group, but the amount of improvement was subtle and the 15DL group might have consisted of a considerable number of "non-responders". Therefore, identifying "responders" by biomarkers and conducting a prospective randomized study is required to validate our findings.

Prevalence of the different lumbar back pain etiologies in Spain: results from a large observational study in 306 centers (the SMILE study)

Background Identification of causes involved in low back pain (LBP) should contribute to improving the clinical management.

P-247 A follow-up results of team management approach for XELOX therapy in patients with advanced/recurrent colorectal cancer: the SMILE Study (Study of Metastatic colorectal cancer to investigate Impact of Learning Effect)

P-247 A follow-up results of team management approach for XELOX therapy in patients with advanced/recurrent colorectal cancer: the SMILE Study (Study of Metastatic colorectal cancer to investigate Impact of Learning Effect)

An observational study of a team management approach for first-line XELOX therapy in patients with advanced/recurrent colorectal cancer: The SMILE study (the study of metastatic colorectal cancer to investigate impact of learning effect).

554 Background: Although oral chemotherapies such as XELOX are widely favored for convenience and flexibility, these have several disadvantages such as drug non-compliance and delayed discovery of adverse events. So we designed a multicenter, prospective, observational study to evaluate the efficacy of supportive interventions in first-line XELOX for colorectal cancer (CRC) patients (pts). Methods: CRC pts undergoing first-line XELOX (+Bevacizumab) therapy practicing one or more of supportive interventions as follows: 1) a telephone follow-up (TF), 2) instruction on dosage and administration by a pharmacist, 3) skin care instruction by a nurse, and 4) pts education by a doctor were eligible. The objective was to evaluate the incident rate of grade 2 or worse hand-foot syndrome (HFS), QoL, safety, and efficacy. QoL was assessed at baseline, 2, 4, 5 and 8 cycles after the treatment started, using the Hospital Anxiety and Depression Scale (HADS) and the Mental adjustment to cancer scale (MAC). Results: From April 2011 to September 2012, 80 pts were enrolled from 14 institutes. The characteristics were as follows: male/female: 46/34, age median: 63 (36-75), and supportive intervention 1)/2)/3)/4): 36/68/73/78. The incidence of grade 2 or worse HFS during 6 months were 11.1% (n=4) for those received TF (n=36), and 20.5% (n=9) for those received other intervention except TF (n=44). Relative dose intensity (RDI) was 75.7% (TF+/-: 77.7/74.3%) in oxaliplatin and 77.5% (TF+/-: 80.2/75.3%) in capecitabine, respectively. Although a tendency of the QoL score improvement about anxiety, fighting spirit and helplessness in a TF group was observed during the periods from start of therapy to 4 courses, there were no significant differences compared to other interventions except TF. Conclusions: We confirmed that HFS incidence was mitigated in a TF group. In regard to QoL, although we could not show the statistical differences due to some limitations of this study such as small sample size and non-randomized, it was indicated that TS had the potential to improve several QoL about anxiety, fighting spirit, and helplessness. Clinical trial information: UMIN000007185.

Effectiveness and adverse events of tolvaptan in octogenarians with heart failure. Interim analyses of Samsca Post-Marketing Surveillance In Heart faiLurE (SMILE study).

The vasopressin receptor 2 (V2) receptor antagonist tolvaptan is an aquaretic agent that has been found to improve symptoms in patients with congestive heart failure. In this study (SMILE study), we administered tolvaptan to patients aged ≥ 80 years with heart failure accompanied by congestive symptoms and compared its effectiveness and safety profiles in this group with those in patients < 80 years (U-80). The results showed that the effectiveness of tolvaptan in the aged patients was similar to that in U-80 patients. In the safety profile, the incidence rate of thirst was lower in the aged patients than that in U-80 patients (9.6% versus 11.6%, P = 0.0023). Furthermore, the incidence of hypernatremia, defined as ≥ 150 mEq/L in aged patients, was comparable with that in U-80 patients (2.9% versus 3.6%, respectively, P = 0.3657). Based on these findings, tolvaptan has similar effectiveness and safety profiles in aged patients compared with U-80 patients. In addition, we found that a higher starting dose of tolvaptan was markedly associated with the occurrence of hypernatremia exclusively in the aged population; therefore, we recommend that tolvaptan should be started at lower doses in aged patients.