Re-challenge chemotherapy with gemcitabine plus carboplatin in patients with non-small cell lung cancer.

Despite recent improvements to current therapies and the emergence of novel agents to manage advanced non-small cell lung cancer (NSCLC), the patients' overall survival remains poor. Re-challenging with first-line chemotherapy upon relapse is common in the management of small cell lung cancer but is not well reported for advanced NSCLC. NSCLC relapse has been attributed to acquired drug resistance, but the repopulation of sensitive clones may also play a role, in which case re-challenge may be appropriate. Here, we report the results of re-challenge with gemcitabine plus carboplatin in 22 patients from a single institution who had previously received gemcitabine plus platinum in the first-line setting and had either partial response or a progression-free interval of longer than 6 months. In this retrospective study, the charts of patients who underwent second-line chemotherapy for NSCLC in our cancer center between January 2005 and April 2010 were reviewed. All the patients who received a combination of gemcitabine and carboplatin for re-challenge were included in the study. These patients were offered second-line treatment on confirmation of clear radiological disease progression. The overall response rate was 15% and disease control rate was 75%. The median survival time was 10.4 months, with 46% of patients alive at 1 year. These results suggest that re-challenge chemotherapy should be considered in selected patients with radiological partial response or a progression-free survival of longer than 6 months to the initial therapy.

Effectively training pediatric residents to deliver diagnoses of Down syndrome.

Physicians and parents report a need for pediatricians to have additional training in delivering a diagnosis of Down syndrome (DS). This study tested a web-based tutorial to assess its effectiveness in improving physicians' perceived comfort with both ambiguous and more medically factual situations as they deliver diagnoses of DS. Based on this web tutorial that integrated prenatal and postnatal information into virtual patient scenarios, the study assessed pediatrics residents' knowledge and comfort in delivering a diagnosis of DS pre and postnatally. A separate survey, given at the same time, asked for residents' perception of their need for this training. Ninety-one volunteer residents from 10 pediatric training programs across the country participated. The tutorial yielded significant improvement in knowledge and a significant decrease in perceived level of discomfort in both ambiguous situations and more medically certain contexts related to a DS diagnosis. In addition, across all pediatric resident groups (by year, gender, and performance on the knowledge test and the comfort scale), residents strongly agreed that this type of training was beneficial for themselves, other residents, practicing physicians, and other medical professionals. This study suggests that web-based, interactive, multi-media training may be an effective tool for improving resident physician comfort with both ambiguous and more medically certain situations in delivering a diagnosis of DS to families.

Afatinib treatment in advanced non-small cell lung cancer.

Despite some recent advances in the management of advanced non-small cell lung cancer (NSCLC), prognosis for these patients remains poor. Small molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have however provided a new therapeutic option in this disease setting and EGFR mutation testing is now routine practice for newly diagnosed NSCLC patients. A proportion of patients will not respond to first-generation EGFR-TKIs however, and those who do will ultimately develop resistance and disease relapse. Next-generation EGFR-TKIs which inhibit multiple members of the EGFR family are being developed in order to increase sensitivity and overcome resistance to existing agents. Afatinib (BIBW 2992) is an oral, irreversible inhibitor of EGFR and HER2 tyrosine kinases and is the most advanced of these agents in clinical development. Pre-clinical and early-phase clinical trials have demonstrated a favorable safety profile as a single agent and in combination with other anti-cancer agents, and provide evidence of clinical activity in advanced NSCLC. The LUX-Lung trials suggest that for selected patients, afatinib offers symptomatic improvement and prolonged progression-free survival, although this has not yet translated into improved overall survival. This article aims to review the use of EGFR-TKIs in the management of advanced NSCLC and the mechanisms underlying resistance to these agents. We will discuss the current pre-clinical and clinical data regarding afatinib, its potential to overcome resistance to first-generation TKIs, and its emerging role in advanced NSCLC treatment.

Gefitinib for the treatment of non-small-cell lung cancer.

IMPORTANCE OF THE FIELD: The epidermal growth factor receptor (EGFR) is a leading target for treatment of non-small-cell lung cancer (NSCLC). Recent trials of the small-molecule EGFR inhibitor gefitinib have now more clearly defined indications for usage, and clinical and molecular factors predictive of benefit. AREAS COVERED IN THIS REVIEW: A systematic search of the literature (Medline, ASCO, WCLC meeting abstracts) was performed from January 2000 to January 2010. The Phase III INTEREST study found gefitinib in unselected, pretreated patients was not inferior to docetaxel chemotherapy in overall survival, offering improved quality of life and superior toxicity profile. The Phase III IPASS study demonstrated improved progression-free survival with gefitinib compared with paclitaxel-carboplatin chemotherapy in chemotherapy-naive, never/light ex-smokers with adenocarcinoma histology. Stratifying for EGFR mutation revealed mutation-positive patients had superior outcomes with gefitinib compared with chemotherapy. Subsequent studies (WJOG4305, NEJ002), selecting only EGFR mutation-positive patients prospectively confirm this finding. WHAT THE READER WILL GAIN: The profile of gefitinib and landmark trials in NSCLC are summarized. How biomarkers may further optimize therapeutic benefit is highlighted. TAKE HOME MESSAGE: Gefitinib is expected to have an important impact on management of pretreated and selected chemotherapy-naive patients with advanced NSCLC. In addition, activating EGFR mutations are proven to be of value for prediction of those who will derive most benefit.

Improving residents' understanding of issues, comfort levels, and patient needs regarding screening for and diagnosing Down syndrome.

OBJECTIVE: This study assessed obstetrics and gynecology and pediatrics residents' knowledge about Down syndrome (DS) and their comfort in delivering a prenatal or postnatal diagnosis of DS before and after interaction with a web-based tutorial. STUDY DESIGN: A team of physicians, parents, and educational specialists developed an interactive tutorial that asked resident physicians to provide their own responses to "virtual patient" cases related to DS diagnoses in utero and at birth. We tested resident knowledge and comfort-level changes and their satisfaction with the web-based tool. RESULTS: The study yielded significant improvement in knowledge and level of comfort changes with both obstetrics and gynecology and pediatric resident physicians at 16 programs nationally. There were no significant differences between the 2 specialties. CONCLUSION: This interactive tutorial is effective in improving physicians' knowledge of and comfort level with imparting accurate, balanced information about DS pre- and postnatally.

Resident physicians' competencies and attitudes in delivering a postnatal diagnosis of Down syndrome.

OBJECTIVE: This study responded to the need expressed by physicians and parents alike for improved medical information and support to families upon the initial diagnosis of Down syndrome at birth. The purpose was to assess obstetrics and gynecology and pediatrics residents' cognitive knowledge about Down syndrome and comfort in counseling parents with a newborn child with Down syndrome before and after intervention (resident viewing and interaction with the educational material). METHODS: A team of physicians, parents, and educational specialists developed an interactive CD-ROM that asked resident physicians to read and view virtual patient-doctor sessions, and provide their own responses to critical situations related to Down syndrome diagnoses. The research tested both knowledge and attitude change, as well as the effectiveness of an interactive CD-ROM as a pedagogical tool. RESULTS: Our effectiveness study yielded positive and significant improvement in knowledge and level of comfort changes with both obstetrics and gynecology and pediatric physicians in residence at the University of Kentucky. Residents also found the technologically based interactive type of instruction to be usable and valuable. CONCLUSION: Teaching physicians to impart accurate and balanced information about Down syndrome at the initial point of diagnosis can be achieved, in part, through training with the CD-ROM. From a broader perspective, this effectiveness study suggests the potential applications of these communication strategies not only to families who have a child with Down syndrome, but also to those with other life-altering disabilities. LEVEL OF EVIDENCE: II-3.

Training pediatric residents to provide smoking cessation counseling to parents.

The objective was to assess the effectiveness of a smoking cessation educational program on pediatric residents' counseling. Residents were randomly selected to receive the intervention. Residents who were trained were compared to untrained residents. Self-reported surveys and patient chart reviews were used. Measures included changes in self-reported knowledge, attitudes and behaviors of residents, and differences in chart documentation and caretaker-reported physician counseling behaviors. The intervention was multidimensional including a didactic presentation, a problem-solving session, clinic reminders, and provision of patient education materials. Results showed that residents who were trained were more likely to ask about tobacco use in their patients' households. They were also more likely to advise caretakers to cut down on or to quit smoking, to help set a quit date, and to follow up on the advice given at a subsequent visit. Trained residents were more likely to record a history of passive tobacco exposure in the medical record. These residents also reported improved confidence in their counseling skills and documented that they had done such counseling more often than did untrained residents. Caretakers of pediatric patients who smoke seen by intervention residents were more likely to report that they had received tobacco counseling. Following this intervention, pediatric residents significantly improved their behaviors, attitudes, and confidence in providing smoking cessation counseling to parents of their pediatric patients.