tbuckley/cabot-search huggingface dataset:
Taxanes as neoadjuvant chemotherapy (NAC) for breast cancer (BC): Pooled-analysis of 3120 patients (Pts) enrolled in 10 randomized trials (RCTs)
Authors: A. Felici, E. Bria, G. Ferretti, P. Carlini, M. Ciccarese, F. L. Cecere, C. Nisticò, F. Cognetti, E. Terzoli, D. Giannarelli
Journal: Journal of Clinical Oncology (2005)

682 Background. Pathological complete response (pCR) achievement is crucial for increasing survival in BC after NAC. Morevoer, a significant pCR difference is currently considered as major end-point of many ongoing RCTs designed to assess the benefit of new drugs over old or standard regimens. The benefit of taxanes as NAC is still unclear. We performed a pooled analysis of RCTs, to look if taxanes-based NAC adds some advantage over standard treatment. Methods. All published and presented RCTs were considered eligible. A literature-based pooled-analysis was accomplished, and event-based relative risk ratios (RR) with 95% confidence interval (CI) were derived. We looked at significant differences in: pCR, CR, pCR excluding ductal carcinoma in situ (DCIS), rate of conservative surgery (Lump.), axillar nodal complete response (Node neg.), G3–4 febrile neutropenia (FN) and neutropenia. Combined effect estimation was computed with both random- and fixed- effect model. An heterogeneity (het.) test was applied. Results. Ten RCTs between 1998 and 2004 (3120 pts) were gathered; pts and results are in the table below: When ruling out 2 RCTs in which pts did not received anthracyclines with taxanes as NAC, RR for pCR was 1.66 (95% CI 1.39–1.98, p<0.001, het. p=0.012, pts: 2475), and for CR 1.51 (95% CI 1.36–1.66, p<0.001, pts: 2741), without significant heterogeneity (p=0.50). Neutropenia results were heterogenous and not significant. Conclusions. Although considering the drawbacks of a pooled analysis and the significant heterogeneity in some outcome, taxanes as NAC for BC seem to significantly increase pCR and CR rate. No significant financial relationships to disclose.
Safety and quality of life (QoL) findings from a randomized phase III study of capecitabine (X) + oxaliplatin (O) (XELOX) vs. infusional 5-FU/LV + O (FOLFOX-6) in metastatic colorectal cancer (MCRC)
Authors: M. Hebbar, J. Bennouna, V. Boige, M. Ychou, G. Lledo, A. Adenis, R. Faroux, C. Rebischung, J. Douillard, T. Conroy
Journal: Journal of Clinical Oncology (2007)

4099 Background: A recent phase III trial in first-line MCRC showed that XELOX is non-inferior to infusional 5-FU + oxaliplatin (FOLFOX-4) for progression-free survival (PFS) [Cassidy ESMO 2006]. Here we present safety and QoL findings from a study of XELOX vs. FOLFOX-6 in first-line MCRC. Methods: Between 16 May 03 and 31 Aug 04, 306 patients (pts) were randomized to receive either XELOX (156 pts: × 1,000mg/m 2 bid d1–14, O 130mg/m 2 d1, q3w) or FOLFOX-6 (150 pts: O 100mg/m 2 d1 LV 400mg/m 2 2h infusion then 5-FU 400mg/m 2 i.v. bolus then 2,400–3,000mg/m 2 46h infusion, q2w) for 6 months. Primary objective: demonstrate non inferiority of XELOX in terms of best response rate (RECIST). Secondary objectives: evaluate QoL and pt satisfaction with care by EORTC QLQ-C30 and FACIT (chemotherapy convenience and satisfaction) questionnaires. Pts completed questionnaires at baseline, before cycles 3/4, 6/8 and at final visit in XELOX/FOLFOX-6 arms, respectively. Results: 245 pts (QLQ-C30) and 225 pts (satisfaction) were evaluable for QoL. The compliance rate was &gt;70%. At baseline, QoL scores were not significantly different. QLQ-C30 functional and symptomatic scores were stable in both arms. According to FACIT, there was no difference between arms, although XELOX-treated pts wasted less hours of their free time than those on FOLFOX-6: 10±23 vs. 37±68 hours, respectively (p=0.007). XELOX was a more ‘comfortable’ treatment (p&lt;0.001 vs. FOLFOX-6 at 2nd evaluation and p=0.009 at 3rd evaluation). Safety profile was acceptable in both arms. In the safety population (n=304), XELOX pts had more grade 3/4 hand-foot syndrome (3 vs. 1% p=0.215), thrombocytopenia (12 vs. 5% p=0.052) and diarrhea (12% vs. 7% p=0.1), but less grade 3/4 febrile neutropenia (0 vs. 6% p=0.001) and neuropathy (8 vs. 19% p=0.003) than those on FOLFOX-6. Treatment discontinuation for toxicity was 19% and 23% for XELOX and FOLFOX-6 arms, respectively. Conclusions: XELOX is comparable to FOLFOX-6 in terms of QoL with less time wasted receiving XELOX. XELOX is also non-inferior to FOLFOX-6 (primary endpoint met/presented at same meeting) with a similar safety profile in first-line MCRC. No significant financial relationships to disclose.
A phase II prospective study evaluating the role of pemetrexed plus gemcitabine (Pem/Gem) chemotherapy as intial treatment in patients with stage IIIB/IV non-small cell lung cancer (NSCLC) using a genomic predictor of cisplatin-resistance to guide therapy
Authors: J. Garst, M. Datto, J. E. Herndon, W. T. Barry, D. Shoemaker, A. Bjurstrom, C. Andrews, G. Ginsburg, J. R. Nevins, A. Potti
Journal: Journal of Clinical Oncology (2008)

8108 Background: Platinum-based combination chemotherapy is the standard of care for advanced NSCLC despite response rates in Phase III trials of 18%. We designed a novel phase II study evaluating the role of pemetrexed/gemcitabine (Pem/Gem) combination chemotherapy in patients predicted to be cisplatin-resistant based on a genomic signature. Methods: An 80 gene signature predicting resistance to cisplatin has been described (Hsu, et al, JCO, 2007) and validated with an accuracy of >85% in independent in vitro and retrospective patient studies. A fresh, frozen tissue biopsy is obtained from each patient and used for Affymetrix assays to predict cisplatin- sensitivity/resistance with an average turnaround time of 6 days. Patients predicted to be cisplatin-sensitive are assigned to the Cis/Gem treatment arm and patients predicted to be cisplatin-resistant are assigned to the Pem/Gem treatment arm. Results: Sixteen patients have been screened since 5/2007 with 7 screen failures due to inadequate or poor quality RNA or excluded histology. Of 9 treated patients, 67% were predicted to be cisplatin-resistant. Toxicities on the Pem/Gem arm include one each Gd3 diarrhea, confusion, FN, pleural effusion and pneumonia. Cis/Gem toxicities include Gd3 nausea and vomitting. One patient has died due to progressive disease. There have been no unexpected or Gd4/5 toxicities. Conclusions: Genomic expression profiles can be used to predict cisplatin-resistance in NSCLC and guide the use of customized chemotherapy in a timely manner. We expect an accrual of 30 pts by ASCO 2008. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Lilly Lilly
Anti-IL-6 and PD-L1 antibody combination therapy reduces tumor progression in murine models of pancreatic cancer
Authors: Thomas Mace, Reena Shakya, Jason Pitarresi, Shannon Loftus, Benjamin Swanson, Gregory Young, Xioling Zhong, Teresa Zimmers, Michael Ostrowski, Thomas Ludwig, Mark Bloomston, Tanios Bekaii-Saab, Gregory Lesinski
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Checkpoint inhibition has gained traction as an immunotherapeutic approach. However, limited efficacy has been observed in patients with pancreatic ductal adenocarcinoma (PDAC). Prior studies by our group have indicated that human pancreatic stellate cells (PSC), a major component
Abstract 18643: Longterm Mortality in 272 Women with Peripartum Cardiomyopathy
Authors: Anders Barasa, Annika Rosengren, Lars Ladfors, Karl Swedberg, Maria Schaufelberger
Journal: Circulation (2012)

Introduction: Peripartum cardiomyopathy (PPCM) is new-onset unexplained dilated cardiomyopathy with heart failure (HF) during the last months of pregnancy and the months following delivery. Prognosis and clinical course is highly variable and overall mortality in hospitalized cases unknown. Purpose: To determine long term mortality and predictors of outcome in women with PPCM in Sweden. Methods: Through linking records from the Hospital Discharge Registry and Medical Birth Registry (MBR), cases eligible for inclusion were identified from subjects with a pregnancy associated HF or PPCM diagnosis. To determine time and mode of death, these were further linked to the Cause of Death Registry. Controls (5:1) matched for age and year of diagnosis were allocated from the MBR. Results: From 1987 to 2010, we included 272 PPCM cases (1341 controls) with an average incidence rate of 1 in 9,191 live births (1 in 18,142 (1987-1991), and 1 in 6,549 (1996-2010)). A total of 22 cases and 5 controls died during the study period. Mean follow-up was 16.4 years. One-, 3-, 5- and 10-year all cause mortality was 4.0%, 5.9%, 5.9% and 7.0% among cases, and 0%, 0%, 0.15% and 0.22% among controls respectively (fig). The odds ratio (OR) of a fatal outcome in women with PPCM compared to controls was 23.5 (95%CI = 8.8; 62.6). Mortality among cases declined from 22.6% (1987-1996) to 3.8% (1997-2010), OR 5.93 (95%CI = 2.37; 14.78) for the first compared to the last period. Conclusions: PPCM mortality was lower than indicated in previous reports from USA, but still much higher than in healthy controls. Deaths leveled off after 3 years from diagnosis. Though incidence more than doubled, mortality continued to decline.
Avoiding unnecessary arterial blood sampling in COPD exacerbations: a stab in the right direction
Authors: Andrew W Hitchings, Emma H Baker
Journal: Thorax (2016)

Hospital admissions for exacerbations are major events in the lives of people with COPD. The prognosis for such patients is grim. Around one in seven will die within 3 months of admission, and fewer than half will still be alive at 5 years.1 ,2 The symptoms they experience are frightening and unpleasant,3 their quality of life is reduced4 and the restriction in their physical activity, which may persist for weeks after the onset of symptoms, increases the risk that they will become housebound.5 In comparison with other medical emergencies, such as myocardial infarction and stroke, progress in improving the management of COPD exacerbations has been depressingly slow. Arguably, the last major advance was the introduction of non-invasive ventilation, which took place sometime in the latter part of the last century. Against this backdrop, it is vital that, as a clinical and research community, we should tenaciously pursue all opportunities to improve the experience for these patients. In doing this, we must reflect critically on our existing practice and the pain and burdens it may present for those who endure it. In this issue of Thorax , McKeever et al 6 do just this, by questioning the need for an investigation that many of us would consider almost sacrilegious to omit: the arterial blood gas.

Learning and refining the technique of arterial blood sampling is a rite of passage for medical students, junior doctors and increasingly other healthcare professionals. Evidence of their efforts is perhaps most conspicuous among the inpatient COPD population, where masses of haphazardly taped cotton-wool balls adorn the increasingly purpuric wrists of these unfortunate individuals. As McKeever et al have observed, the pain associated with arterial blood …
Interest of check-up before discontinuing anti thrombotic therapy after a first episod of pulmonary embolism
Authors: Elodie Collinge, Richard Frognier
Journal: European Respiratory Journal (2013)

Although numerous pulmonary embolism (PE) guidelines are available, there is still concern about specific point of management. Interest of checkup before discontinuing anti thrombotic therapy (ATT) in eligible patients is one of this question. To investiguate this we have retrospectively studied all patients treated for PE in our unit during two consecutive years. We have identified 100 cases of PE of which 84 first episod. Among this 84 patients, 3 died during hospitalisation (3,6%). Among the 81 survivors, 25 (31%) underwent a 3 months checkup, 2 (2%) died between the 3rd and 6th month, 15/79 (19%) underwent a 6 months checkup, 19/81 (23%) haven’t had follow up, 20/81 (25%) have had anarchical follow up. Among the 25 patients who underwent a 3 months checkup, 18 (72%) have realised a ventilation & perfusion scintigraphy (VPS), 6 (24%) an angio CT, 6 (24%) an echocardiography and 3 (12%) a veinous doppler of the legs (VDL). Treatment was discontinued for 8 (32%) and maintain for 12 (48%). There wasn’t information in 5 cases (20%). Among the 15 patients who underwent a 6 months checkup, 6 (40%) have realised a VPS, 5 (33%) an angio CT, 7 (47%) an echocardiography and none (0%) a VDL. Treatment was discontinued for 13 (87%) and maintain for 2 (13%). This study shows that a great number of exams are realised in order to discontinue the ATT after a first episod of PE while only 1/3 is discontinued in the patients who underwent a checkup at three months and nearly 9/10 in the patients who underwent a 6 months checkup. This study emphasises the need of strong data in order to determine if a checkup is required to discontinue an ATT after a first episod of pulmonary embolism.
Temporal Trends of Digoxin Use in Patients Hospitalized With Heart Failure
Authors: Nish Patel, Christine Ju, Conrad Macon, Udho Thadani, Phillip J. Schulte, Adrian F. Hernandez, Deepak L. Bhatt, Javed Butler, Clyde W. Yancy, Gregg C. Fonarow
Journal: JACC Heart Failure (2016)
Abstract 073: Late Onset of Wolff-Parkinson-White Syndrome in a 48 year old Post-Menopausal Woman
Authors: Shane D Bush
Journal: Circulation Research (2013)

Introduction— First described in 1930, Wolff-Parkinson-White syndrome, or WPW syndrome, is an abnormal extra electrical pathway in the heart that can lead to tachycardia, palpitations and rarely sudden cardiac death. The extra electrical pathway of Wolff-Parkinson-White syndrome is present at birth and is a congenital heart abnormality occurring in about 1 per 1,000. Young men have a higher incidence of WPW than women. Episodes of tachycardia often first occur when they are in their teens or early 20s. The definitive treatment of WPW is a destruction of the abnormal electrical pathway by radiofrequency catheter ablation with success rates of as high as 95%. If radiofrequency catheter ablation is successfully performed, the condition is generally considered cured. Recurrence rates are typically less than 5% after a successful ablation. Case description— A 48 year old post-menopausal woman with intermitted palpitations and syncope over approximately one month which were affecting her daily activities presented to our family practice center complaining of worsening palpitations and new onset tachycardia. An EKG revealed a positive delta wave. Unique features were late onset diagnosis at age of 48 year old post-menopausal female without any previous documentation of WPW syndrome on an EKG. WPW is usually diagnosed in men in their early 20’s. Additional cardiac workup included a 24hr Holter monitor; exercise EKG treadmill test and transthoracic echocardiography which helped confirm the initial diagnosis. The patient had catheter ablation approximately two months after the first symptoms appeared. The procedure involved a Thermocool ® catheter and 3D electroanatomic mapping using the Ensite ® system which led to a successful ablation of the accessory pathway. Discussion— This case involves a very rare condition with an atypical late onset. WPW is normally diagnosed in men at a young age. The unique and rare features of this case were the recent onset of palpitations, syncope and tachycardia, evolving at a fairly advanced age of 48 years old, without any previous documentation of WPW syndrome in an ECG. The patient also had a full recovery and had no further symptoms of palpations, syncope and tachycardia since undergoing the catheter ablation surgery.
Rationale and evidence for the use of sunitnib to treat patients with malignant paraganglioma/pheochromocytoma (MPP)
Authors: A. M. Joshua, R. Broom, M. Milosevic, M. Jewett, A. Evans, S. Asa, I. F. Tannock, J. J. Knox
Journal: Journal of Clinical Oncology (2008)

14681 Background: Malignant paragangliomas and pheochromocytomas (MPP) are rare tumors that are associated with germline mutations in the gene encoding the Krebs cycle enzyme, succinate dehydrogenase (Baysal et al., 2000). The resultant tumors overexpress HIF-1α and have activation of HIF1α targets (such as VEGF) and high microvessel density. The accumulation of succinate is thought to inhibit HIF prolyl hydroxylases, thereby stabilising HIF-1α. The putative mechanism of tumorigenesis is a pseudo-hypoxic drive, similar to that in the von Hippel-Lindau syndrome. (Selak et al., 2005). We hypothesise that similar to renal cell carcinoma, therapeutic agents targeted to this pathway will have activity against MPP. Results: We report 2 patients with MPP who have demonstrated a RECIST partial response to sunitnib: one with a locally advanced juxtarenal primary (that was subsequently rendered resectable) and one in the metastatic setting (bladder primary). Molecular and immunohistochemical analyses of tumor and germline tissue will be presented. Conclusions: There is a sound rationale for treating patients with MPP with sunitinib and preliminary clinical evidence of its activity. A multi-institutional phase 2 trial is planned. No significant financial relationships to disclose.
Activity of the cyclin-dependent kinase (CDK) inhibitor flavopiridol in relapsed, genetically high risk chronic lymphocytic leukemia (CLL)
Authors: T. S. Lin, L. A. Andritsos, J. A. Jones, B. Fischer, N. A. Heerema, K. A. Blum, J. M. Flynn, M. E. Moran, M. A. Phelps, M. R. Grever, J. C. Byrd
Journal: Journal of Clinical Oncology (2008)

7007 Background: The targeted CDK inhibitor flavopiridol induces p53-independent apoptosis in CLL cells. We demonstrated the activity of flavopiridol in relapsed, high risk CLL in a phase I study of a pharmacokinetically derived dosing schedule (Lin et al, Blood 108: 93a, 2006; Byrd et al, Blood 109: 399, 2007). We report a phase II trial to confirm these findings. Methods: Patients (pts) with relapsed CLL with WBC < 200 x 109/L received flavopiridol by 30-min IV bolus (IVB) followed by 4-hr continuous IV infusion (CIVI). Pts received 30 mg/m2 IVB + 30 mg/m2 CIVI for dose 1, with escalation to 30 mg/m2 IVB + 50 mg/m2 CIVI beginning at dose 2. Therapy was given weekly for 4 doses every 6 weeks for up to 6 cycles. The study was amended to change the schedule to 3 doses every 4 weeks to improve tolerance. Results: Sixty-two pts were enrolled. Median age was 61 years (range, 31–82), 40 were male (65%), and 11 were > 70 years. Median number of prior therapies was 4 (range, 1–11). All pts had failed purine analog therapy. Rai stage was I/II (n=14) or III/IV (n=48). Three pts did not undergo dose escalation due to grade 4–5 tumor lysis with dose 1, and 2 pts required dialysis. Cytokine release syndrome (CRS) was common and was associated with IL-6 release, but was averted by use of pre-treatment dexamethasone. Pts received a median of 4 cycles (range, 0.25–6), 15 pts completed all 6 cycles, and 6 continue therapy. Thirty pts responded (48%) by NCI 96 criteria, with 26 partial responses (42%) and 4 complete responses (6.5%) including 1 pt with del(17p13) and a complex karyotype. Responses were seen in 9 of 18 pts (50%) with del(17p13), 11 of 28 pts (39%) with del(11q22), and 10 of 25 pts (40%) with a complex karyotype. Overall, 19 of 44 pts with high-risk cytogenetics (43%) and 21 of 44 pts with lymph nodes > 5 cm responded (48%). Of 26 pre-amendment pts, 2 completed therapy and 10 responded (38%). In contrast, 13 of 36 post-amendment pts completed 6 cycles and 20 responded (56%). Conclusions: The targeted CDK inhibitor flavopiridol has pronounced clinical activity in relapsed CLL pts including pts with bulky adenopathy and poor-risk cytogenetics such as del(17p13). Prophylactic steroids eliminated IL-6 release and CRS, allowed more pts to complete therapy, and resulted in a higher response rate. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis
Results of 27 years of phase III trials for patients with extensive-disease small-cell lung cancer
Authors: I. Oze, K. Kiura, K. Hotta, N. Ochi, Y. Fujiwara, N. Takigawa, M. Tabata, T. Shinkai, M. Tanimoto
Journal: Journal of Clinical Oncology (2009)

e19021 Background: Few studies have formally assessed whether treatment outcomes for patients with extensive-disease small-cell lung cancer (ED-SCLC) enrolled in Phase III trials have improved substantially over the years. This investigation determined the trends in the outcomes for the patients in those trials. Methods: We analyzed trials that were reported between January 1991 and August 2008. Phase III randomized controlled trials were eligible if they compared first-line, systemic chemotherapy for ED-SCLC. Data were evaluated using linear regression analysis. Results: We identified 55 trials initiated between 1980 and 2006, involving 10,407 patients with 116 chemotherapy arms. The number of randomized patients and the proportions of patients with good performance status (PS) increased with the passage of time. In the 1990s, increasing numbers of studies examined cisplatin-based regimens, especially cisplatin and etoposide (PE) regimens, while decreasing numbers examined cyclophosphamide, doxorubicin, and vincristine-based regimens. A scattergram of the parameters ‘year of trial initiation’ and ‘median survival time’ (MST) indicated that MST increased 0.024 months (0.71 days) per year (P = 0.198). The multiple regression analysis showed no significant survival improvement over the years (regression coefficient for the year of trial initiation = 0.004, P = 0.980). In addition, the use of PE regimens did not prolong survival, whilst the proportion of good PS patients and the assignment of prophylactic cranial irradiation were significantly associated with favorable outcomes. Conclusions: The survival of patients with ED-SCLC enrolled in phase III trials has not improved significantly over the years, suggesting the need for a breakthrough, such as the discovery of novel molecular targets. No significant financial relationships to disclose.