tbuckley/cabot-search huggingface dataset:
Phase II trial of docetaxel and gefitinib as first-line therapy for elderly patients with advanced non-small cell lung cancer (ANSCLC)
Authors: C. C. Williams, E. B. Haura, S. J. Antonia, A. Chiappori, G. Bepler, G. R. Simon
Journal: Journal of Clinical Oncology (2004)

7342 Background: Currently chemotherapy with two cytotoxic drugs is considered standard treatment for ANSCLC. We hypothesized that doublet therapy with a cytotoxic drug (docetaxel) and an EGFRTKI (gefitinib) will yield a more favorable toxicity profile but without compromising efficacy. We report here the preliminary data from an on going phase II trial combining docetaxel and gefitinib in elderly (≥ 70 years) patients with ANSCLC. Methods: Previously untreated patients were eligible. Docetaxel was administered at a dose of 75mg/m2 on day 1. Gefitinib was administered orally daily at a dose of 250 mg starting on day 1. Treatment was repeated every 21 days. The RECIST criteria were used to measure response.Functional status was assessed using the Lawton and Brodys Instrumental Activities of Daily Living(IADL). The Cumulative Illness Rating Scale adapted to Geriatric patients (CIRS-G) was used to assess comorbidities. Results: From August 2003 to November 2003 12 patients have been enrolled on this trial. Eleven patients are assessable for toxicity and 10 patients are assessable for response. Patients characteristics are the following M/F = 9/3; Median age 74 years (range 70 to 82 years); ECOG PS 0/1= 4/8 and Stage IV/IIIB = 11/1. Preliminary response rate is 50% out of 10 evaluable patients; CR=0, PR=5(50%). SD=3 (30%), PD=2(20%). Most common treatment related non-hematologic adverse events were fatigue, rash and diarrhea all of which grade 1 or 2. Most common hematologic adverse events were grade II neutropenia and grade II anemia. Serious adverse events include 4 hospitalizations; 1 each for DVT, non-neutropenic staphylococcal pneumonia and non-neutropenic bacterial pneumonia and COPD exacerbation. No episode of febrile neutropenia has been reported to date. Three deaths have occurred so far two from progressive disease and one from bacterial pneumonia. Conclusions: Preliminary analysis suggests that the combination of docetaxel and gefitinib appears be promising with a favorable toxicity profile in a population of elderly patients with ANSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis Aventis; AstraZeneca
Complete response rates with lenalidomide plus rituximab for untreated indolent B-cell non-Hodgkin's lymphoma.
Authors: N. H. Fowler, P. McLaughlin, F. B. Hagemeister, L. W. Kwak, M. A. Fanale, S. S. Neelapu, L. Fayad, R. Z. Orlowski, M. Wang, F. Samaniego
Journal: Journal of Clinical Oncology (2010)

8036 Background: The optimal treatment for newly diagnosed indolent non-Hodgkins lymphoma (NHL) has not been determined. While several combination chemotherapy regimens have response rates approaching 90%, toxicity is common with genotoxic drugs. Lenalidomide has been shown to have single-agent activity in indolent NHL, and is approved for the treatment of multiple myeloma and myelodysplastic syndrome. Rituximab is effective alone and in combination with chemotherapy for indolent NHL. The aim of this phase II study was to evaluate the efficacy and safety of lenalidomide and rituximab in patients (pts) with untreated, stage III/IV, indolent NHL. Methods: Pts with measurable (>1.5 cm) untreated indolent NHL received 20 mg/day of lenalidomide on days 1-21 and rituximab 375 mg/m2 on day 1 of each 28 day cycle for up to 6 cycles. Response was assessed after 3 and 6 cycles using the International Working Group Response Criteria. Results: At the time of this report, initial planned accrual of 30 patients was complete. The median age was 56 (36-77) years, 57% of pts were male, and 28 pts were evaluable for response. The overall response rate was 86%. Complete responses (CR) were attained in 79% (65% CR/14% CRu) of pts, 2 pts (7%) had a partial response, and stable disease was seen in 4 (14%). Response rates were impressive in follicular lymphoma, with nearly all patients 16/17 (94%) attaining a CR. At a median follow up of 14.1 (9.7-18.8) months, one patient experienced progression of disease. The following grade 3/4 adverse events were reported: rash (6 pts), neutropenia (7 pts), myalgia (4 pts), neuropathy (1 pt), infection (1 pt), fatigue (1 pt), and thrombosis (1 pt). Two pts were removed from treatment due to adverse events but were eligible for toxicity assessment, including 1 with grade 3 rash, and 1 with arterial thrombosis, both of which occurred in cycle 1. Conclusions: The biologic agents lenalidomide and rituximab used as front line therapy produces excellent overall and complete response rates in pts with indolent B cell NHL. Based upon these results, planned accrual has been increased to 110 patients, and 58 patients have been enrolled to date. The response and toxicity data will be presented in their updated form. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene Biogen Idec, Genentech Celgene
Cisplatin, vincristine, and fluorouracil therapy for hepatoblastoma: a Pediatric Oncology Group study.
Authors: E C Douglass, M Reynolds, M Finegold, A B Cantor, A Glicksman
Journal: Journal of Clinical Oncology (1993)

PURPOSE To estimate the disease-free survival rate in children with grossly resected hepatoblastoma treated with cisplatin, vincristine, and fluorouracil (CDDP/VCR/FU) and to assess the disease-response rate and disease-free survival (DFS) rate in children with unresectable or metastatic tumors treated with this combination. PATIENTS AND METHODS Sixty assessable patients with hepatoblastoma received therapy with five (stage I and II) to seven (stage III and IV) courses of CDDP (90 mg/m2), day 1, and VCR (1.5 mg/m2), and FU (600 mg/m2), day 3. RESULTS Nineteen of 21 patients with stage I or II disease survive free of disease (actuarial survival, 90% at 5 years). Twenty-four of 31 patients with stage III disease achieved a complete remission (CR) after chemotherapy and surgical excision; actuarial DFS at 4 years is 67%. Only one of eight patients with stage IV disease achieved a remission and survives. CONCLUSION Relatively brief exposure to chemotherapy with CDDP/VCR/FU provided excellent disease control to patients with grossly resected tumors. In patients with initially unresectable disease, this therapy provides a response rate and DFS rate comparable to regimens that contain doxorubicin (DOX).
Integrative approaches for large-scale transcriptome-wide association studies
Authors: Alexander Gusev, Arthur Ko, Huwenbo Shi, Gaurav Bhatia, Wonil Chung, Brenda W J H Penninx, Rick Jansen, Eco J C de Geus, Dorret I Boomsma, Fred A Wright, Patrick F Sullivan, Elina Nikkola, Marcus Alvarez, Mete Civelek, Aldons J Lusis, Terho Lehtimäki, Emma Raitoharju, Mika Kähönen, Ilkka Seppälä, Olli T Raitakari, Johanna Kuusisto, Markku Laakso, Alkes L Price, Päivi Pajukanta, Bogdan Pasaniuc
Journal: Nature Genetics (2016)
Safety and effectiveness of home-based pulmonary rehabilitation in COPD
Authors: A Dushianthan
Journal: Thorax (2009)

Despite overwhelming evidence to suggest that pulmonary rehabilitation improves health status in patients with chronic obstructive pulmonary disease (COPD), this service is largely underutilised due to poor accessibility. This Canadian multicentre randomised study was designed to compare outpatient pulmonary rehabilitation with self-monitored home-based rehabilitation in improving dyspnoea.

Patients with stable COPD (forced expiratory volume in 1 s …
Fortnightly review: The muscular dystrophies
Authors: A. E H Emery
Journal: BMJ (1998)

In 1954 based on their own detailed clinical studies and an extensive review of the earlier literature, Walton and Nattrass1 proposed a new and valuable classification of the muscular dystrophies. Ten years later Walton reviewed advances in the subject in the BMJ . 2 3 Many developments have taken place since then during a period in which there have been important advances in the application of molecular biology to medicine. Using protein studies and gene studies it is possible in the majority of cases to establish the precise diagnosis of a particular type of dystrophy, and thus provide a prognosis as well as genetic counselling and a reliable prenatal diagnosis. These developments could hardly have been imagined 30 years ago.

#### Summary points

The muscular dystrophies are a heterogeneous group of inherited disorders characterised by progressive muscle wasting and weakness

The genes and the protein products that are responsible for the dystrophies have been identified for most types of dystrophy

Using muscle protein studies and molecular genetic studies in the majority of cases it is possible to establish a precise diagnosis, provide a prognosis, detect preclinical cases, identify carriers, and offer prenatal diagnostic testing

The quality of life of individuals with dystrophy can be much improved by a positive attitude to management which includes respiratory care, physiotherapy, and the surgical correction of contractures

A molecular genetic approach seems to offer the best prospect for developing effective treatment in the future

This brief review is partly based on a survey of the most recent literature and partly based on nearly 40 years of personal clinical and research experience of these disorders. During the past 10 years the European Neuromuscular Centre, now based in the Netherlands, has encouraged and coordinated both clinical and laboratory studies of dystrophy, many of which have led directly or indirectly to the advances …
Assessment of hot flashes and clinical correlates in breast cancer patients receiving tamoxifen or third-generation aromatase inhibitors
Authors: L. Morales, P. Neven, E. Cheroutre, G. vande Putte, R. Paridaens
Journal: Journal of Clinical Oncology (2005)

8015 Background: The aim of this study was to assess prevalence and severity of hot flashes in breast cancer patients with or without endocrine treatment and to identify patients at risk in whom interventions may be necessary. Methods: 233 postmenopausal breast cancer patients belonging to various stages were included in this cross-sectional study. They completed local treatments and chemotherapy for at least 3 months and were without evidence of disease progression on inclusion. Current hormonal treatments were: None, 58 pts; tamoxifen, 79 pts; FEMTA trial (double blind adjuvant tamoxifen vs letrozole) 49 pts; letrozole, 26 pts; exemestane, 21 pts. Frequency and severity of hot flashes and other menopausal symptoms were recorded in a 14-day diary. Statistical analysis was done with non-parametric test Mann-Whitney U test and Pearson’s correlation test. Results: Prevalence of hot flashes was highest under tamoxifen (70%) and in the FEMTA trial (69%). Hot flashes were less frequent in patients without hormonal therapy (52%) and in patients under aromatase inhibitors (49%), both groups being significantly different than patients receiving tamoxifen (p=0.054 and p= 0.013, respectively). No significant difference in hot flashes was seen when comparing aromatase inhibitors vs no hormonal therapy, or tamoxifen vs FEMTA. Age was inversely correlated with occurrence of hot flashes (p< 0.0001). Patients with lower educational level and those in partnered relationships reported more hot flashes (all p≤ 0.046). Moreover, the occurrence of hot flashes was significantly correlated to the presence of nervousness and depressive mood (p=0.02) and was associated with other menopausal symptoms such as vaginal dryness (p=0.073) and memory problems (p=0.072). Conclusions: Although hot flashes are most severe under tamoxifen, a significant proportion of patients receiving third generation aromatase inhibitors and even untreated patients experience this symptom. This underscores the need for finding effective and safe non-hormonal interventions. No significant financial relationships to disclose.
Abstract 12561: Validation of Score System Excluding Female Gender From CHA <sub>2</sub> DS <sub>2</sub> -VASc in Japanese Patients With Non-Valvular Atrial Fibrillation: A Subanalysis of the J-RHYTHM Registry
Authors: Hirofumi Tomita, Ken Okumura, Hiroshi Inoue, Hirotsugu Atarashi, Takeshi Yamashita, Hideki Origasa, Eiki Tsushima
Journal: Circulation (2014)

Recent American and European guidelines recommend CHA 2 DS 2 -VASc (VASc) score for thromboembolic risk stratification in patients with non-valvular atrial fibrillation (NVAF), which includes female gender (Sc) as a risk. Although we validated this score in Japanese NVAF patients (Circ J 2014), our recent analysis showed that female gender is not a risk in this population (Am J Cardiol 2014). In the present analysis, we evaluated the score system excluding female gender from VASc in Japanese NVAF patients enrolled in J-RHYTHM Registry. We prospectively assessed the incidence of systemic thromboembolism (SE) for 2 years in 997 Japanese NVAF patients without warfarin treatment (mean age, 68±12 years, 294 females). VASc score was determined, in which V was replaced by coronary artery disease (Co). Another score excluding female gender was defined as CHA 2 DS 2 -VA, or CHA 2 DS 2 -CoA (CoA). The predictive value of VASc and CoA scores for SE was compared by the c-statistics and the Net Reclassification Improvement (NRI). SE occurred in 7/294 females (1.2%/year) and 23/703 males (1.6%/year) (odds ratio 0.72, 95% confidence interval (CI) 0.28-1.62, p=0.44). Overall, there were no differences in the c-statistic and NRI between VASc and CoA scores (c-statistic 0.66, 95%CI 0.55-0.75, and 0.64, 0.54-0.74, respectively, p=0.76, and NRI 0.064, 95%CI -0.091-0.218, p=0.42). In male patients of VASc score 0, 1, and &gt;2, SE occurred in 2/141 (0.7%/year), 4/194 (1.0%/year), and 17/368 (2.3%/year), respectively, and in females of VASc score 1 and &gt;2, it occurred in 0/39 (0%/year) and 7/255 (1.4%/year), respectively. In female patients of CoA score 0, 1, and &gt;2, SE occurred in 0/39 (0%/year), 1/51 (1.0%/year), and 6/204 (1.5%/year), respectively. There was a trend to be a significant NRI between the two scores in this stratification (NRI 0.059, -0.008-0.126, p=0.08). Finally, only in patients of VASc score 0 and 1 (n=374), there were significant differences in the c-statistic and NRI between VASc and CoA scores (c-statistic 0.52, 95%CI 0.32-0.72, and 0.58, 0.37-0.76, respectively, p&lt;0.0001, and NRI 0.106, 95%CI 0.075-0.137, p&lt;0.0001). These findings indicate that CoA, a score excluding female gender from VASc, is useful for thromboembolic risk stratification in Japanese NVAF patients.
Relationship between H1N1 induced asthmatic symptoms and airway hyperresponsiveness in children
Authors: Yoon Hee Kim, Jiyoung Baek, Hyun Bin Park, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim
Journal: European Respiratory Journal (2011)

Purpose:  H1N1 infection is known as an important aggravating factor of asthma. However, there is no report about airway hyperresponsiveness (AHR) in patients who developed H1N1 induced acute asthmatic symptoms without previous asthma. The aim of this study was to investigate whether moderate to severe asthmatic symptoms induced by H1N1 were related with AHR in patients without previous asthma.   Methods:  We studied children less than 15 years old visited for H1N1 infection in Severance Children9s Hospital from August in 2009 to February in 2010. H1N1 infection was confirmed by real-time RT-PCR analyzing the products of nasopharyngeal swab when the patients had fever and acute respiratory symptoms like cough, rhinorrhea, and sore throat. Among the infected children, patients hospitalized due to acute asthmatic symptoms like dyspnea or wheezing sound were enrolled. We performed methacholine challenge test one month after discharge. AHR was defined as PC 20  below 16 mg/mL.   Results:  Total number of H1N1-infected children was 4,362 (age of 6.95±3.75). Male to female ratio was 56.88%. Two hundred eighty seven patients (6.58%, age of 5.83±3.75) were hospitalized due to respiratory complications. Among them, 76 patients without previous asthma showed acute asthmatic symptoms (26.48%). Forty six patients were performed methacholine challenge test. Only 17 (36.96%) patients presented AHR.   Conclusion:  H1N1 infection induced acute asthmatic symptoms not only in patients with asthma, but also in patients without previous asthma. H1N1 induced moderate to severe asthmatic symptoms might tend to be temporary and would not contribute to AHR.
A phase I safety and tolerability study of vorinostat (V) in combination with sorafenib (S) in patients with advanced solid tumors, with exploration of two tumor-type specific expanded cohorts at the recommended phase II dose (renal and non-small cell lung carcinoma).
Authors: A. Dasari, L. Gore, W. A. Messersmith, S. Diab, A. Jimeno, C. D. Weekes, K. D. Lewis, H. A. Drabkin, T. W. Flaig, D. R. Camidge
Journal: Journal of Clinical Oncology (2010)

2562 Background: S is a multitargeted kinase inhibitor approved in renal cancer with investigational activity in NSCLC. Preclinical studies suggest synergy with the HDAC inhibitor V. Methods: 3+3 dose escalation design to determine MTD and RP2D of V 200-400mg QD days (D) 1-14 as an investigational agent with S (400 mg BID D1-21) in 21 D cycles done in patients (pts) with advanced malignancies, ECOG PS 0-2 and intact organ function. Pts with < 85% cycle 1 dosing in absence of DLTs were replaced. Dose escalation when <2/3-6 dose limiting toxicities (DLTs). DLT = non-hem toxicity ≥ grade (Gr) 3 or hem toxicity ≥ Gr 4, or drug discontinuation for >14 days due to drug-related toxicities in cycle 1. MTD confirmed as RP2D if tolerable in 6 pts through 2 cycles. RP2D then explored in expanded cohorts in RCC and NSCLC (12 pts each). Results: Dose escalation is complete (17 pts: 3 mesothelioma; 3 NSCLC; 2 each CRC, soft tissue sarcoma and RCC; 3 other). Median age 60 (range 48–76), M:F 9/8, ECOG PS 0/1 (3/14). At 400 mg S/400 mg V, 2/4 pts experienced DLT (Gr 2 hand foot syndrome [1] and multiple Gr 1 toxicities [x1] causing drug discontinuation >14 days). At 400 mg S/300 mg V, 6/6 pts completed ≥ 2 cycles without DLT. Treatment-related toxicities available in 17 pts were mostly Gr 1- 2: rash (9 pts), fatigue (7), anorexia (7), diarrhea (7), nausea (7), dysguesia (6). Gr 3 toxicities were fatigue, thrombocytopenia and dry skin (1 each). No drug-related deaths or Gr 4 toxicities were noted. Of 12 pts evaluable by RECIST, 1 pt with renal sarcoma had an unconfirmed partial response (31% decrease). 9 had stable disease, all with minor responses (1-26% decrease) (2-11+ cycles, 7-32 + weeks), including 1 RCC (26%), 1 NSCLC (21%), and 1 leiomyosarcoma (20%). Conclusions: The MTD/RP2D of the combination is V 300 mg QD D1-14 and S 400 mg BID D1-21 in 21 D cycles. Preliminary clinical activity has been observed in a heavily pretreated pt population. Enrollment to the tumor-type specific cohorts continues. Updated results will be presented. No significant financial relationships to disclose.
Accommodating Bigotry
Authors: Meghan Lane-Fall
Journal: JAMA (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The relative influence of clinical information, financial incentives, and other factors on physician’s choice of chemotherapy
Authors: S. J. Johnson, J. H. Bilenker, A. J. Epstein
Journal: Journal of Clinical Oncology (2006)

6002 Background: Understanding the effect of financial incentives for specialty pharmaceuticals on physician choice has been a priority for policy makers. This research seeks to identify the extent to which published clinical information and financial incentives affect a physician’s choice of chemotherapy along with other factors. Methods: SEER-Medicare and Medispan pricing data were formed into a panel of 4,503 patients who were diagnosed with metastatic breast cancer and treated with chemotherapy from 1991 to 2002. A conditional logit discrete choice model was employed to analyze the effects of product attributes, including financial margin, volume of randomized controlled trial citations, FDA labeled indications, years since launch, generic status, and other covariates, on odds of choice of chemotherapy. A chemotherapy-level fixed effects specification was used to analyze choices of drug in patients’ first and subsequent drug administrations. Results: The natural log of clinical information was positive and significant (β = 1.270; p &lt; 0.001); a one unit increase in log of citations increased odds of choice by 27 percent, all else constant. Physicians avoided generics (β = 0.703; p &lt; 0.01), preferred on- to off-label drugs (β = 0.468; p &lt; 0.01), and preferred older drugs to newer ones. Financial incentives for the first chemotherapy administration were positive and significant influences on choice of drug (β = 1.001; p &lt; 0.001). A $100 increase in reimbursement per day increased the odds of choosing a drug by 10 percent. Preference for financial incentives, more clinical information, and on-label drugs declined in subsequent administrations. Conclusions: This research provides evidence that financial incentives have a positive but modest effect on the average physician’s choice of chemotherapy when treating metastatic breast cancer. New clinical information about a drug also had a positive effect on choice. [Table: see text]