Personalized and adaptive learning: educational practice and technological impact

Education Technology advances many aspects of learning. More and more learning is taking place online. Learners’ learning behaviors, style, and performance can be easily profiled through learning analytics which collects their online learning footage. It enables and encourages educational research, learning software application development, and online education practices towards personalized and adaptive learning. As we continue to see personalized and adaptive learning progress, we must also pay attention to the negative impacts that feed into our research. In this paper, we will present our introspection of personalized and adaptive learning and argue that it is the social and moral responsibility of educators and institutions to apply personalized and adaptive learning wisely in their education practice. Educators and institutions should also recognize the realistic diversities of individual students’ learning styles and variable learning progress, contextually dependent learning accessibility, and their correspondent support needs for the fine-grained learning activities. We argue that the strategically balanced practices and innovated learning technology are crucial towards an optimized learning experience for the learners. A Tecnologia da Educação avança muitos aspectos da aprendizagem. Cada vez mais aprendizagem está ater lugar online. Os comportamentos de aprendizagem, estilo e desempenho dos aprendentes podem serfacilmente perfilados através de análises de aprendizagem que recolhem as suas filmagens de aprendizagemon-line. Permite e encoraja a investigação educacional, o desenvolvimento de aplicações de software deaprendizagem, e práticas de educação em linha para uma aprendizagem personalizada e adaptativa. À medidaque continuamos a ver progressos na aprendizagem personalizada e adaptativa, devemos também prestaratenção aos impactos negativos que alimentam a nossa investigação. Neste documento, apresentaremos anossa introspecção de aprendizagem personalizada e adaptativa e argumentaremos que é da responsabilidade social e moral dos educadores e instituições aplicar sabiamente a aprendizagem personalizada e adaptativa nasua prática educativa. Os educadores e as instituições devem também reconhecer as diversidades realistas dosestilos de aprendizagem dos estudantes individuais e o progresso variável da aprendizagem, a acessibilidade àaprendizagem contextualmente dependente, e as suas necessidades de apoio correspondente para as actividadesde aprendizagem de grão fino. Argumentamos que as práticas estrategicamente equilibradas e a tecnologiade aprendizagem inovadora são cruciais para uma experiência de aprendizagem optimizada para os alunos

Pooled analyses of eribulin in metastatic breast cancer patients with at least one prior chemotherapy.

Based on data from two multicenter, phase III clinical trials (Studies 301 and 305), eribulin (a microtubule dynamics inhibitor) is indicated in the European Union (EU) for patients with locally advanced or metastatic breast cancer (MBC) after ≥1 prior chemotherapy for advanced disease, including an anthracycline and a taxane in either the adjuvant or metastatic setting. Data from Studies 305 and 301 were pooled to investigate the efficacy of eribulin in various subgroups of patients who matched the EU label, including those with human epidermal growth factor receptor 2 (HER2)-negative and triple-negative disease. In Study 305 (NCT00388726), patients were randomized 2:1 to eribulin mesylate 1.4 mg/m(2) (equivalent to eribulin 1.23 mg/m(2) [expressed as free base]) intravenously on days 1 and 8 every 21 days] or treatment of physician's choice after 2-5 prior chemotherapies (≥2 for advanced disease), including an anthracycline and a taxane (in early/advanced setting). In Study 301 (NCT00337103), patients were randomized 1:1 to eribulin (as above) or capecitabine (1.25 g/m(2) orally twice daily on days 1-14 every 21 days) following ≤3 prior chemotherapies (≤2 for advanced disease), including an anthracycline and a taxane. Efficacy end points were investigated in the intent-to-treat population and subgroups, pooled as discussed above. Overall, 1644 patients were included (eribulin: 946; control: 698); baseline characteristics were well matched. Overall survival was significantly longer with eribulin versus control (P < 0.01), as were progression-free survival and clinical benefit rate (both P < 0.05). Significant survival benefits with eribulin versus control were observed in a wide range of patient subgroups, including HER2-negative or triple-negative disease (all P < 0.05). Our findings underline the survival benefit achieved by eribulin used according to EU label in the overall MBC population and in various subgroups of interest, including patients with HER2-negative and triple-negative disease

Сравнение эффективности применения трастузумаба в течение 6 и 12 мес в адъювантном режиме при лечении пациенток с ранним HER2+ раком молочной железы в рандомизированных исследованиях III фазы

Представленырезультаты многоцентровых клинических исследований, на основании которых применение трастузумаба в течение 12 мес в адъювантном режиме было регламентировано в США и Европе как стандарт при лечении пациенток с ранним HER2+ раком молочной железы (РМЖ). Приведены данные многоцентрового рандомизированного клинического исследования фазы III (PHARE, NCT00381901), целью которого было сравнение эффективности применения трастузумаба в течение 6 или 12 мес по принципу «noninferiority». Результаты этого исследования, полученные при медиане периода наблюдения 42 мес, не подтвердили предположения, что применение трастузумаба для адъювантной терапии в течение 6 мес у пациенток с ранним HER2+ РМЖ не менее эффективно, чем в течение 12 мес, хотя при сокращении длительности лечения несколько снижается уровень кардиотоксичности.The results of multicenter clinical trial on the basis of 12-month adjuvant use of trastuzumab administered in the US and Europe as a standard in the treatment of patients with early HER2+ breast cancer are presented. The data of a multicenter rando mized clinical trial, phase III (PHARE, NCT00381901), the purpose of which was to compare the efficacy of trastuzumab for 6 months or 12 months on the principle of «non-inferiority» are considered. The results of this study obtained under a median follow-up 42 months, did not confirm the assumption that the adjuvant use of trastuzumab for 6 months in patients with early HER2+ breast cancer is not less effective than at 12 months, although the reduction in the duration of treatment is somewhat reduced level of cardiotoxicity

A unified definition of clinical anthracycline resistance breast cancer

The purpose of the study was to determine the response rates (RR) and duration to second- and third-line chemotherapy programmes in patients with anthracycline-resistant breast cancer, utilizing various definitions of anthracycline resistance. This was a retrospective analysis performed on 1335 patients with metastatic breast cancer who participated in consecutive clinical trials of first line, anthracycline-containing combination chemotherapy (ACCC) at the University of Texas MD Anderson Cancer Center between July 1973 and April 1980. Anthracycline-resistant groups were identified using definitions of anthracycline resistance found in the literature: progressive disease as best response to ACCC (Group 1, n = 56 patients); progressive disease while receiving ACCC after an intervening response to the drug (Group 2, n = 84); progressive disease within 6 months of last dose of ACCC (Group 3, n = 233); and progressive disease within 12 months of last dose of ACCC (Group 4, n = 272). Second- and third-line therapies administered to these patients included methotrexate, doxorubicin, mitoxantrone, bisantrene, vinblastine, vindesine, melphalan, mitomycin, cisplatin, etoposide and others, but not taxanes. The distribution of patients' characteristics was similar between the four groups, as was the use of second- and third-line regimens. Response rate (RR) to second-line chemotherapy were 5% and 7.7% for Group 1 and Group 2 respectively. In contrast, RR to second-line chemotherapy were 21.6% and 15% for Group 3 and 4. The differences in response rate between the combination of Groups 1 and 2 and Groups 3 or 4 were significant (P = 0.005 and P = 0.04 respectively). These results indicate that strictly defined anthracycline resistance as defined in Groups 1 and 2 is associated with resistance to many other cytotoxic drugs. The definitions used in Groups 3 and 4 include many patients with responsive tumours, and a more favourable prognosis. © 2000 Cancer Research Campaig

Efficacy and safety of subcutaneous trastuzumab and intravenous trastuzumab as part of adjuvant therapy for HER2-positive early breast cancer: final analysis of the randomised, two-cohort PrefHer study

Aim To assess efficacy (event-free survival, EFS) and safety in patients followed up for 3 years in the PrefHer study (NCT01401166). Patients and methods Post surgery and post chemotherapy in the (neo)adjuvant setting, patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer were randomised to receive four cycles of the subcutaneous form of trastuzumab (Herceptin ® SC [H SC] via single-use injection device [Cohort 1] or delivery via a hand-held syringe from an SC Vial [Cohort 2]; 600 mg fixed dose) followed by four of the intravenous form of trastuzumab (Herceptin ® [H IV]; 8 mg/kg loading, 6 mg/kg maintenance doses) in the adjuvant setting or vice versa every 3 weeks. Patients could have received H before randomisation. H was then continued to complete a total of 18 cycles, including any cycles received before randomisation. Results A total of 488 patients were randomised across both cohorts. After median follow-up of 36.1 months, 3-year EFS across both groups in the evaluable intention-to-treat population (467 patients) was 90.6% overall, 89.9% in Cohort 1, and 91.1% in Cohort 2. No new safety signals were identified during long-term follow-up, with only one cardiac serious adverse event in the safety population (483 patients). Conclusions Three-year EFS data following H SC and H IV treatment are consistent with those reported by previous trials for H in the adjuvant setting. The overall safety profile during adjuvant treatment was as expected

Three-year follow-up from a phase 3 study of SB3 (a trastuzumab biosimilar) versus reference trastuzumab in the neoadjuvant setting for human epidermal growth factor receptor 2-positive breast cancer

Background: We assessed long-term cardiac safety and efficacy in patients with human epidermal growth factor receptor 2–positive early breast cancer treated with a trastuzumab biosimilar (SB3) or its reference product, trastuzumab (TRZ), in a phase 3 study. Methods: Patients who completed the phase 3 study could be enrolled in this extension study. The outcomes included the incidence of symptomatic congestive heart failure (CHF), asymptomatic significant left ventricular ejection fraction (LVEF) decrease, incidence of other cardiac events, event-free survival (EFS), and overall survival. In post hoc analysis, the Cox proportional hazards regression model was used to assess factors associated with EFS. Results: A total of 367 patients were enrolled in the study (SB3, n = 186; TRZ, n = 181). The median follow-up duration from the main study enrolment was 40.8 and 40.5 months for SB3 and TRZ, respectively. During the two-year follow-up after adjuvant therapy, incidence of asymptomatic significant LVEF decrease was rare (SB3, n = 1; TRZ, n = 2), with all patients recovering with LVEF ≥ 50%, and no cases of symptomatic CHF or other cardiac events were reported. At 3 years, the EFS was 91.9% with SB3 and 85.2% with TRZ. The number of patients with events was 17 (9.1%) with SB3 and 31 (17.1%) with TRZ [hazard ratio: 0.47, 95% confidence interval: 0.26–0.87]. Antibody-dependent cell-mediated cytotoxicity (ADCC) activity and the breast pathologic complete response rate were the factors associated with EFS. Conclusion: Cardiotoxicity was rare in this extension study. EFS was higher with SB3 versus TRZ, with post hoc analysis suggesting that a downward drift in ADCC activity was a contributing factor

PF-05280014 (a trastuzumab biosimilar) plus paclitaxel compared with reference trastuzumab plus paclitaxel for HER2-positive metastatic breast cancer: a randomised, double-blind study

BACKGROUND: This randomised, double-blind study compared PF-05280014 (a trastuzumab biosimilar) with reference trastuzumab (Herceptin®) sourced from the European Union (trastuzumab-EU), when each was given with paclitaxel as first-line treatment for HER2-positive metastatic breast cancer. METHODS: Between 4 April 2014 and 22 January 2016, 707 participants were randomised 1:1 to receive intravenous PF-05280014 plus paclitaxel (PF-05280014 group; n = 352) or trastuzumab-EU plus paclitaxel (trastuzumab-EU group; n = 355). PF-05280014 or trastuzumab-EU was administered weekly (first dose 4 mg/kg, subsequent doses 2 mg/kg), with the option to change to a 3-weekly regimen (6 mg/kg) from Week 33. Treatment with PF-05280014 or trastuzumab-EU could continue until disease progression. Paclitaxel (starting dose 80 mg/m2 ) was administered on Days 1, 8 and 15 of 28-day cycles for at least six cycles or until maximal benefit of response. The primary endpoint was objective response rate (ORR), evaluating responses achieved by Week 25 and confirmed by Week 33, based on blinded central radiology review. RESULTS: The risk ratio for ORR was 0.940 (95% CI: 0.842–1.049). The 95% CI fell within the pre-specified equivalence margin of 0.80–1.25. ORR was 62.5% (95% CI: 57.2–67.6%) in the PF-05280014 group and 66.5% (95% CI: 61.3–71.4%) in the trastuzumab-EU group. As of data cut-off on 11 January 2017 (using data up to 378 days post-randomisation), there were no notable differences between groups in progression-free survival (median: 12.16 months in the PF-05280014 group vs. 12.06 months in the trastuzumab-EU group; 1-year rate: 54% vs. 51%) or overall survival (median: not reached in either group; 1-year rate: 89.31% vs. 87.36%). Safety outcomes and immunogenicity were similar between the treatment groups. CONCLUSION: When given as first-line treatment for HER2-positive metastatic breast cancer, PF-05280014 plus paclitaxel demonstrated equivalence to trastuzumab-EU plus paclitaxel in terms of ORR. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT0198967

Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck

This phase II study determined response rate of patients with locally advanced or metastatic head and neck cancer treated with pemetrexed disodium, a new multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. 35 patients with local or metastatic relapse of squamous cell carcinoma of the head and neck (31 male, 4 female; median age 53 years) were treated with pemetrexed 500 mg m2 administered as a 10-minute infusion on day 1 of a 21-day cycle. Patients received 1 to 8 cycles of therapy. 9 patients (26.5%) had an objective response, with a median response duration of 5.6 months (range 2.9–20 months). 15 (44.1%) had stable disease, and 8 (23.5%) had progressive disease. 2 patients were not assessable for response. Median overall survival was 6.4 months (range 0.7–28.1 months; 95% CI: 3.9–7.7 months). 24 patients (68.6%) experienced grade 3/4 neutropenia, with febrile neutropenia in 4 (11.4%). Grade 3/4 anaemia and thrombocytopenia occurred in 11 (34.3%) and 6 (17.1%) patients, respectively. The most frequent non-haematological toxicity was grade 3/4 mucositis (17.1%; 6 patients). In conclusion, pemetrexed is active in squamous cell carcinoma of the head and neck. Although substantial haematological toxicities were experienced by patients, subsequent studies have shown that these toxicities can be proactively managed by folic acid and vitamin B12 supplementation. © 2001 Cancer Research Campaign http://www.bjcancer.co