tbuckley/cabot-search huggingface dataset:
Safety, tolerability, and efficacy of the first-in-class antibody IMAB362 targeting claudin 18.2 in patients with metastatic gastroesophageal adenocarcinomas.
Authors: Martin H. Schuler, Zanete Zvirbule, Florian Lordick, Anna Krilova, Ulrike Helbig, Henning Schulze-Bergkamen, Peter C. Thuss-Patience, Goetz von Wichert, Karsten Schulmann, Tanja Trarbach, Stefan Bauer, Christian Mueller, Salah-Eddin Al-Batran, Christoph Huber, Ugur Sahin, Oezlem Tureci
Journal: Journal of Clinical Oncology (2013)

4080 Background: IMAB362 is a monoclonal antibody targeting isoform 2 of the tight junction component claudin 18 (CLDN18.2), a tumor-selective antigen frequently expressed in several types of epithelial adenocarcinomas. Preclinically, IMAB362 exerts its antitumor activity by ADCC, CDC, induction of apoptosis and inhibition of cell proliferation. Methods: Patients with treatment-refractory, metastatic gastroesophageal adenocarcinomas with CLDN18.2-positive tumors as determined by immunohistochemistry were enrolled in two clinical trials of IMAB362 monotherapy. A phase I inter-patient single dose escalation study (n=15, 5 dose groups from 33 mg/m² to 1000 mg/m² with 3 patients each, follow-up 4 weeks) was conducted followed by a phase II study (n=34, 300 mg/m 2 [n=4] and 600 mg/m 2 [n=30]) administered every two weeks for 5 courses, imaging in week 11. Patients with disease control allowed to continue IMAB362 therapy until progression. Analysis of the phase II trial is ongoing. Results: In the phase I trial, all dose levels of IMAB362 were generally well tolerated. Nausea and vomiting were the most common adverse events (AEs). No dose limiting toxicity was observed at single doses up to 1,000 mg/m². Based on pharmacokinetic considerations and preclinical dose/response data, the recommended doses for the phase II multidose trial was 600 mg/m². In the phase II study, 34 patients were evaluable for safety. No grade 4 AEs occurred, grade 3 AEs were vomiting (n=8, 24%), nausea (n=4, 12%) and hypersensitivity (n=1, 3%). As of January 2013, 31 patients were evaluable for efficacy analysis. Four patients had achieved a confirmed partial response, and eight patients had disease stabilization (ORR=13%, DCR=39%). The longest observed response duration thus far was 40 weeks. Conclusions: IMAB362 antibody therapy of patients with advanced CLDN18.2-positive gastroesophageal adenocarcinomas is safe and well tolerated. Early evidence for antitumoral activity was observed in the phase II trial. Further clinical evaluation of IMAB362 in patients with CLDN18.2 tumors is warranted. Clinical trial information: NCT01197885.
A genomic strategy to combinatorial therapeutics in solid tumors
Authors: A. Potti, H. K. Dressman, A. Bild, R. Riedel, M. Kelley, G. Ginsburg, J. Lancaster, J. Nevins, P. Febbo
Journal: Journal of Clinical Oncology (2006)

2031 Background: For most advanced solid tumors, the response rate to cytotoxic drugs is generally low, highlighting the importance of identifying those patients most likely to respond, either to single agents or combinations of cytotoxic or targeted therapies. Methods: We have made use of in vitro drug response data generated on the NCI-60 panel of cancer cell lines, coupled with Affymetrix U133 2.0 plus gene expression data, to develop genomic predictors of chemotherapy sensitivity. These models were then validated in independent cancer cell lines as well as response data from patient treatment studies. Results: Predictive models making use of gene expression data were developed for docetaxel, adriamycin, 5-flourouracil, cyclophosphamide, paclitaxel, and topotecan. These models were shown to accurately predict sensitivity to the drugs in an independent set (n = 30) of cancer cell lines. Importantly, three of the predictors (docetaxel, topotecan, paclitaxel) also accurately (&gt; 80%) predicted response in patient studies. When evaluated in a large collection of human cancers (n = 381), these gene expression signatures of drug response identified patterns of predicted sensitivity suggesting potential opportunities for novel combinations. We also combined the predictions of chemotherapy sensitivity with predictions of pathway deregulation (Bild A, Nature 2005), to develop further opportunities for combination therapy. For instance, this analysis revealed a significant relationship between PI3 kinase pathway deregulation and docetaxel resistance (p = 0.001), and a correlation between docetaxel sensitivity and the activation of the Rb/E2F pathway (p = 0.009). Furthermore, cell lines showing an increased probability of PI3 kinase and Rb/E2F activation were also more likely to respond to a PI3 kinase (LY-294002) inhibitor (p = 0.01) or R-Roscovitine (p = 0.03), a cell cycle inhibitor, respectively. Conclusions: The development and validation of chemotherapeutic response predictors, together with oncogenic pathway signatures that can guide the use of targeted agents, provides an opportunity to develop effective combinatorial therapeutic strategies geared to the individual patient. No significant financial relationships to disclose.
Primary non-Hodgkin’s lymphomas of the liver with nodular and diffuse infiltration patterns have different prognoses
Authors: J.-F. Emile, D. Azoulay, J.-M. Gornet, G. Lopes, V. Delvart, D. Samuel, M. Reynès, H. Bismuth, F. Goldwasser
Journal: Annals of Oncology (2001)
A comparison of two models of care for lung cancer
Authors: R. U. Osarogiagbon, M. Ninan, M. Joshua, O. Bankole, S. Matthew, M. Jahanzeb
Journal: Journal of Clinical Oncology (2008)

17501 Background: Management of lung cancer involves multiple specialists which can delayed, fragment and impair care. Multi- disciplinary(multi-D) programs improve care by enabling shared-decision making. Setting up multi-D clinics (MDC) is difficult. A multi-D thoracic oncology conference (MD-TOC) involving key specialists may achieve the same benefits. Multi-D approaches depend on timely compliance with recommendations. Methods: Retrospective comparison of all initial recommendations and actual initial clinical practice at a tertiary care Hospital MD-TOC in 2 sequential time periods. Cohort A: MD-TOC alone (Februrary 2006 to February 2007; cohort B: MDC + MD-TOC (March 2007 to September 2007). Groups compared with Fisher-Freidman-Halton test. Results: Cohort A vs B. N = 48 vs 89. All results in percentages. Female gender 52% v 36%. Race (black/ white/other) 69/27/4 vs 50/47/3; employment status (employed/ unemployed/ retired) 21/13/33 vs 26/29/37; health insurance status (third-party/government/uninsured) 40/19/22 vs 18/57/25. Histology (adeno/squamous/large/small) 47/35/2/4 v 44/20/4/10. Stage (IA-IIB/IIIA/IIIB-IV) 16/15/70 vs 34/12/51. All p>0.05. MD-TOC recommendations (cohort A vs B, %): further imaging 17 vs 26; diagnostic biopsy 12 vs 20; staging biopsy 14 vs 5; surgical resection 10 vs 20; chemotherapy and/or radiation therapy (cXRT) 40 vs 19. Interventional procedure recommended: CT biopsy 18 vs 6; bronchoscopy 12 vs 11%; mediastinoscopy 35 vs 20%; thoracoscopy 0 vs 31%; thoracotomy 11 vs 23%. Rate of discordance between MD-TOC recommendation and clinical decision was 28% vs 19%. Discordance rates: imaging 33 vs 5%; diagnostic or staging biopsy 36% vs 25%; surgical resection 25 vs 24%; cXRT 27% vs 24%. Discordance with specific interventions included bronchoscopy 0% vs 0%; mediastinoscopy 50% vs 29%. Discordance with recommendations for major surgical interventions (mediastinoscopy+ thoracoscopy+ thoracotomy) was 42% vs 20%. Conclusions: A high rate of discordance between MD-TOC recommendations and clinical practice exists which may dilute the benefit of this approach. Implementing a group clinic may diminish discordance, even in this poorly insured Urban population in the Southern USA. No significant financial relationships to disclose.
Effects of increase gradual OVA doses in the inhalations in a model of asthma to long term
Authors: Ronaldo Aparecido da Silva, Francine Maria de Almeida, Clarice Rosa Olivo, Beatriz Mangueira Saraiva, Milton Arruda Martins, Celso Ricardo Fernandes de Carvalho
Journal: European Respiratory Journal (2011)

Mice are used to develop models of pulmonary allergic disease.

Objective: To evaluate the increase gradual OVA doses in a protocol of experimental asthma.

Methods: Balb/c mice male were divided in Groups: Control, OVA1%, OVA3%, OVA5%. Sensitized animals received i.p.(OVA+Sal+AlumHidrox; Days: 0,14,28,42). Inhalations sessions (OVA+Saline; 3x wk/30min) were performed between 21st and 54th day. The OVA1% group received inhalation with concentration of OVA1%. The OVA3% began with 1% for 3 weeks (wk), in the 4th wk was increased for 3%. The OVA5% began with 1% in the 1st wk, 2sd wk was increased for 2%, 3rd wk with 3%, 4th wk for 4%, 5th wk for 5% of OVA. The Control group received i.p. and Saline inhalations. In the study were evaluated IgE and IgG1 titers by PCA technique, cells in BALF and peribronchial eosinophils, and smooth muscle of the airways for image analyses.

Results: IgE and IgG1 were increased in sensitized groups, but in the groups 3% and 5% the levels were highest and shown increased of cell migrations presented increase of eosinophils, neutrophils and trickiness of the smooth muscle when compared with others two groups (p<0.01), just Group 3% shown high index of peribronchial eosinophils (p<0.01).

![Figure][1] 



Conclusions: Groups OVA3% and OVA5% are more efficient for develop features of experimental asthma, and seems that Group OVA3% develop important increase of eosinophil migration in the airways.

 [1]: pending:yes
Treatment outcomes in patients with extensive stage small cell lung cancer - Experience from a tertiary Indian cancer centre
Authors: R. Bharath, H. Menon, N. S. Ghadyalpatil, K. Prabhash, S. S. Hingmire, N. Karanth, K. Jain, K. Gaikwad, J. P. Agarwal, P. M. Parikh
Journal: Journal of Clinical Oncology (2008)

19129 Background: Small cell lung cancer (SCLC) is an aggressive malignancy associated with early metastasis and mortality. However, its exquisite sensitivity to chemotherapy and radiotherapy allows for durable clinical responses being achieved even in advancedstage. Multimodality approach through combination chemotherapy and radiotherapy remains the cornerstone for its treatment. Methods: Records of patients with extensive stage SCLC treated at our institution from 2003 to 2006 were analyzed. Their responses and time to disease progression were analyzed retrospectively. Results: A total of 26 patients with extensive stage SCLC were available for analysis. All patients were males with age between 44 and 73 years (Median-60 years). Twenty three patients (82.1%) were smokers. Eighteen patients (64.2 %) had distant metastasis at diagnosis with the adrenal gland being the commonest site (39%). Two patients presented with symptoms of superior venacaval obstruction. Twenty six patients (92.8%) received 6 cycles of palliative chemotherapy with 19 (67.8%) receiving Irinotecan -Cisplatin and 7 (25%) receiving Etoposide-Cisplatin combination. Of the 26 patients treated, complete response (CR), partial response (PR) and progressive disease (PD) were seen in 23% (n=6), 30.7% (n=8) and 23% (n=6) respectively, giving an overall response rate (ORR) of 53.8%. Nine patients (34.6%) in either CR or good PR were given prophylactic cranial irradiation (PCI). At a median follow up of 6 months (Range 10 days -25.5 months), 7.1% (n=2) patients remained disease free. The median relapse free survival was 6.44 months (CI- 5.6–7.3 months). Disease progression after an initial response was seen in 65.3% patients (n=12). Two patients died due to chemotherapy related toxicity and six patients were lost to follow up. Conclusions: Chemotherapy can induce good overall responses in extensive stage SCLC. The initial responses are excellent with short time to progression which is highlighted in our series too. The CR rates are comparable to most published series and PCI may offer an advantage in a those patients who do achieve an excellent partial or complete response. No significant financial relationships to disclose.
The long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF): Interim data from the RECAP extension study
Authors: Ulrich Costabel, Carlo Albera, Alan Cohen, Williamson Bradford, Talmadge King, Paul Noble, Steven Sahn, Dominique Valeyre, Roland du Bois
Journal: European Respiratory Journal (2011)

Introduction:  The CAPACITY (CAP) trials were randomized controlled studies evaluating pirfenidone (PFD) in patients with IPF. Pooled data from these studies support a treatment effect on forced vital capacity, progression-free survival, and 6-minute walk distance. To examine the long-term safety of PFD, an open-label extension study for eligible CAP patients was initiated (RECAP). An interim analysis of safety data from RECAP is presented.   Aims and objectives:  Examine the long-term safety of PFD in patients with IPF.   Methods:  Safety data from the RECAP study through Wk 72 were analyzed and compared to pooled safety data from the CAP trials.   Results:  In the CAP studies, 779 patients were randomized to treatment with PFD or placebo for ≥72 weeks. Of these, 603 enrolled in RECAP. At Wk 72 in RECAP, mean exposure to PFD 2403 mg/d across both studies was 2.9 yrs (range, 1–4); 114 patients had received PFD 2403 mg/d for ≥3 yrs. In RECAP, 98.2% of patients reported ≥1 treatment-emergent adverse event (TEAE) compared to 98.6% in CAP, and 32.8% of patients had a serious TEAE compared to 32.8% during CAP. Common AEs in RECAP were similar to those observed in CAP and were generally mild to moderate in severity. The overall incidence of photosensitivity or rash was lower in RECAP than CAP (19.7% vs. 44.4%); however, patients who received placebo during CAP had a higher incidence than those who received PFD (28.1% vs. 12.3%).   Conclusions:  Long-term safety data demonstrate that PFD is safe and generally well tolerated in patients with IPF. Given the unmet medical need and efficacy results from 3 Phase III studies, PFD has a clear role in the treatment of IPF.
Phylogeny of Greya (Lepidoptera: Prodoxidae), based on nucleotide sequence variation in mitochondrial cytochrome oxidase I and II: congruence with morphological data.
Authors: J M Brown, O Pellmyr, J N Thompson, R G Harrison
Journal: Molecular Biology and Evolution (1994)

The phylogeny of Greya Busck (Lepidoptera: Prodoxidae) was inferred from nucleotide sequence variation across a 765-bp region in the cytochrome oxidase I and II genes of the mitochondrial genome. Most parsimonious relationships of 25 haplotypes from 16 Greya species and two outgroup genera (Tetragma and Prodoxus) showed substantial congruence with the species relationships indicated by morphological variation. Differences between mitochondrial and morphological trees were found primarily in the positions of two species, G. variabilis and G. pectinifera, and in the branching order of the three major species groups in the genus. Conflicts between the data sets were examined by comparing levels of homoplasy in characters supporting alternative hypotheses. The phylogeny of Greya species suggests that host-plant association at the family level and larval feeding mode are conservative characters. Transition/transversion ratios estimated by reconstruction of nucleotide substitutions on the phylogeny had a range of 2.0-9.3, when different subsets of the phylogeny were used. The decline of this ratio with the increase in maximum sequence divergence among taxa indicates that transitions are masked by transversions along deeper internodes or long branches of the phylogeny. Among transitions, substitutions of A-->G and T-->C outnumbered their reciprocal substitutions by 2-6 times, presumably because of the approximately 4:1 (77%) A+T-bias in nucleotide base composition. Of all transversions, 73%-80% were A<-->T substitutions, 85% of which occurred at third positions of codons; these estimates did not decrease with an increase in maximum sequence divergence of taxa included in the analysis. The high frequency of A<-->T substitutions is either a reflection or an explanation of the 92% A+T bias at third codon positions.
Cost-minimization analysis of a phase III study of capecitabine + oxaliplatin (XELOX) vs. infusional 5-FU/LV + oxaliplatin (FOLFOX-6) as first-line treatment for metastatic colorectal cancer (MCRC) in the French setting
Authors: G. Perrocheau, J. Bennouna, M. Ducreux, M. Hebbar, M. Ychou, G. Lledo, T. Conroy, A. Adenis, R. Faroux, J. Douillard
Journal: Journal of Clinical Oncology (2007)

4083 Background: A recent phase III trial in first-line MCRC showed that XELOX is well tolerated and non inferior to FOLFOX-4 in terms of progression-free survival (PFS) [Cassidy ESMO 2006]. We conducted a phase III trial of XELOX vs. FOLFOX-6 as first-line treatment for MCRC. Methods: 306 patients were randomized to receive either XELOX (n=156: capecitabine 1,000mg/m 2 bid d1–14, oxaliplatin 130mg/m 2 d1, q3w) or FOLFOX-6 (n=150: oxaliplatin 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 (best response rate, RECIST). A cost minimization has been conducted from the French hospital perspective. The hospitalizations for chemotherapy (drug administration) were compiled and the direct hospital costs estimated using official tariffs of the national ‘PMSI’ database, directly derived from the Diagnosis Related Group (DRG). Results: The ITT population comprises 306 patients (156 on XELOX, 150 on FOLFOX-6). Baseline characteristics were well balanced. Patients received an average of 6.1±2.4 and 9.2±3.2 cycles of XELOX and FOLFOX-6, respectively. The number of hospitalizations was 6.5±2.6 and 9.5±4.1 for XELOX and FOLFOX-6, respectively. The costs of hospitalization for chemotherapy are available for 282 patients (142 in the XELOX arm and 140 in the FOLFOX-6 arm). The average cost of chemotherapy per cycle per patient was 608±446€ in the XELOX arm and 1,043±787€ in the FOLFOX-6 arm (p&lt;0.001). Conclusions: As we have shown in the efficacy and safety abstracts also presented at this meeting, XELOX is non inferior to FOLFOX-6 in terms of best response rate with a comparable safety profile. In addition, XELOX appears to decrease hospital resource consumption compared with FOLFOX-6. No significant financial relationships to disclose.
Autologous Hematopoietic Stem-Cell Transplantation for Relapsed or Refractory Hodgkin's Disease in Children and Adolescents
Authors: K. Scott Baker, Bruce G. Gordon, Thomas G. Gross, Minnie A. Abromowitch, Elizabeth R. Lyden, James C. Lynch, Julie M. Vose, James O. Armitage, Peter F. Coccia, Philip J. Bierman
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine the treatment outcome and clinical factors that are of prognostic significance for children and adolescents with relapsed or refractory Hodgkin's disease (HD) who received treatment with high-dose chemotherapy and autologous hematopoietic stem-cell transplantation (HSCT). PATIENTS AND METHODS: Fifty-three consecutive children and adolescents 21 years of age or younger with relapsed or refractory HD underwent HSCT. RESULTS: At day 100 after transplantation, 29 patients (55%) were in a complete remission or maintained a continuous complete response, six (11%) had a partial response, and 11 (21%) failed to respond or had progressive disease. The failure-free survival (FFS) at 5 years was 31%, and overall survival was 43%. Twenty-one patients died of progressive HD, and nine died secondary to transplantation-related complications, including two secondary leukemias. Prognostic factors important for FFS were normal pretransplantation lactate dehydrogenase levels (5-year FFS = 42%), compared with patients with elevated LDH levels (5-year FFS = 0%) (P &lt; .001), and disease sensitivity at the time of HSCT with FFS in untreated relapse, sensitive disease, and resistant disease 44%, 35%, and 9%, respectively (P = .06). There was no statistically significant difference in FFS or overall survival between age subgroups that were analyzed (&lt; 13, 13 to 18, 19 to 21) or in comparison with an adult cohort. CONCLUSION: HSCT is an effective treatment modality that can result in long-term cures and should be considered for children and adolescents with relapsed HD.
Reports of childhood incest and current behavior of chronically hospitalized psychotic women
Authors: J C Beck, B van der Kolk
Journal: American Journal of Psychiatry (1987)

Of the female patients (N = 26) on a state hospital unit who remained chronically institutionalized and actively psychotic despite psychopharmacologic and psychosocial treatment, 12 (46%) reported histories of childhood incest. These 12 patients were more likely than the others to engage socially with ward staff. A higher proportion had sexual delusions, affective symptoms, substance abuse, suspected organicity, and major mental problems, and they spent more time in seclusion than other patients. The authors acknowledge the difficulty of assessing the accuracy of reports of incest. They discuss the implications of a possible relationship between incest and severe, intractable psychotic disorder.
Influence of adjuvant pretreatment on outcome of FIRE-3 (AIO KRK-0306): A randomized phase III study of FOLFIRI plus cetuximab or bevacizumab as first-line treatment for wild-type (WT) KRAS (exon 2) metastatic colorectal cancer (mCRC) patients.
Authors: Sebastian Stintzing, Dominik Paul Modest, Ludwig Fischer von Weikersthal, Thomas Decker, Alexander Kiani, Ursula Vehling-Kaiser, Salah-Eddin Al-Batran, Tobias Heintges, Christian A. Lerchenmuller, Christoph Kahl, Gernot Seipelt, Frank Kullmann, Martina Stauch, Werner Scheithauer, Swantje Held, Clemens Albrecht Giessen, Markus Hermann Moehler, Andreas Jung, Thomas Kirchner, Volker Heinemann
Journal: Journal of Clinical Oncology (2015)

515 Background: The FIRE-3 study (AIO KRK-0306) was designed to compare the efficacy of FOLFIRI + cetuximab (cet) to FOLFIRI + bevacizumab (bev) as first-line treatment in KRAS WT mCRC patients. FOLFIRI plus cet resulted in comparable overall response rates (ORR) and progression free survival (PFS) when compared to FOLFIRI + bev. Overall survival (OS) was significantly longer in the FOLFIRI + cet arm. Methods: In an exploratory subgroup analysis, patients pretreated with adjuvant chemotherapy were analyzed by Fisher's exact and log rank-test according to tumor response (ORR) and survival data. Patients of the ITT (n=592) and the final RAS wild-type population (n=400) were investigated. Results: See table. Conclusions: Results in patients treated with any adjuvant chemotherapy mirrored those in the whole study population. In adjuvant pretreated RASwt patients a significantly higher ORR was reached in the cet arm when compared to the bev arm (p=0.01). The role of adjuvant treatment on efficacy of first-line therapy remains to be further evaluated. Clinical trial information: NCT00433927. [Table: see text] [Table: see text]