tbuckley/cabot-search huggingface dataset:
Vaccination with EGF active immunotherapy improves survival in advanced non small cell lung cancer (NSCLC) patients: Interim analysis of a randomized phase II trial
Authors: E. Neninger, T. Crombet, M. Osorio, M. Catala, A. Torre, I. Leonard, B. García, P. Marinello, G. González, A. Lage
Journal: Journal of Clinical Oncology (2005)

7210 Background: During the last 9 years, numerous clinical trials have been conducted testing an Epidermal Growth Factor (EGF) active immunotherapy approach in patients with advanced NSCLC. This approach consists of human EGF linked to a carrier protein and administered in an adjuvant. Specifically, the vaccine is composed of human recombinant EGF conjugated to Neisseria meningitides P64K as carrier protein and emulsified in Montanide ISA51. Here, we report partial results from an open label, randomized Phase II trial designed to test immunogenicity, safety and efficacy of the EGF vaccine. Methods: Two groups of unresectable, stage IIIb or IV NSCLC patients were compared. All patients received first line chemotherapy and were then randomized to receive EGF vaccine (Group 1) or best supportive care (Group 2). Each dose contained 50ug EGF administered on days 0, 7, 14, 21, 51 and then monthly. Sera anti-EGF antibody titers as well as plasma EGF concentration [EGF] were measured monthly. Survival was compared between treatment groups. Results: Sixty nine (69%) of vaccinated patients (Group 1) showed seroconversion defined as antibody titer levels at least 2X baseline, while 23% of controls (Group 2) did. Forty five percent (45%) of vaccinated patients had a good antibody response (at least 4X baseline levels and at least 1:4000 sera dilution) while none of the controls did. The geometric mean of maximal antibody titers in Group 1 was 1: 2756 and 1:316 in Group 2. Mean minimal [EGF] was 20 pcg/ml for Group 1 and 60 pcg/ml for Group 2. No serious adverse events were reported. Vaccinated patients survived significantly longer than controls. Group 1 median overall survival was 8.47 months (mean 11.52 months) while Group 2 median overall survival was 4.33 months (mean 7.41 months) (p=0.028). Conclusions: Vaccination with EGF active immunotherapy was safe, immunogenic, and significantly increased survival of advanced NSCLC patients in this study. Further study of this approach is warranted. No significant financial relationships to disclose.
Local superficial hyperthermia in combination with low-dose radiation therapy for palliation of locally recurrent breast carcinoma.
Authors: J Dragovic, H G Seydel, T Sandhu, A Kolosvary, J Blough
Journal: Journal of Clinical Oncology (1989)

From September 1984 through March 1987, 30 patients with locally recurrent breast carcinoma who had been heavily pretreated with conventional modes of therapy (radiation, chemotherapy, and hormonal therapy) were entered into a phase II study of hyperthermia and low-dose irradiation. The purpose of the study was to determine the feasibility, effectiveness, and morbidity of this treatment combination. Radiation therapy was administered twice weekly, 4 Gy per fraction, to a total dose of 32 Gy, with 6 or 9 MeV electrons depending on the thickness of the lesions. Hyperthermia generated by microwave frequencies of 200 to 700 MHz was administered immediately after radiation therapy, with a time and temperature aim of 60 minutes at 43 degrees C. Complete response (CR) was achieved in 17 patients (57%), and partial response (PR) in 11 patients (36%). Response was positively correlated with tumor size; lesions less than 5 cm in diameter achieved CR significantly more frequently than lesions greater than or equal to 5 cm (P less than .001). Eighty percent of the complete responders continued to experience sustained control of the treated site from 6 to 32 months but showed evidence of progressive systemic disease or locoregional progression to the adjacent untreated sites, reflecting the natural history of this disease and extensive dermal lymphatic permeation. True recurrence within the treated volume occurred in three patients. Nonhealing ulceration developed in nine patients and seven of those were associated with persistent tumor. This study confirms the palliative value of hyperthermia in combination with radiotherapy for previously irradiated recurrent chest wall tumors and sets the scene for its comparative clinical evaluation against radiation therapy alone as first line therapy for locally recurrent breast carcinoma.
Oral Versus Intravenous Fluoropyrimidines for Advanced Colorectal Cancer: By Either Route, It’s All the Same
Authors: Robert J. Mayer
Journal: Journal of Clinical Oncology (2001)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.21.4093 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11689576 Oral Versus Intravenous Fluoropyrimidines for Advanced Colorectal Cancer: By Either Route, It’s All the Same Robert J. MayerxRobert J. MayerSearch for articles by this author Show More Dana-Farber Cancer Institute, Boston, MA https://doi.org/10.1200/JCO.2001.19.21.4093 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Compliance and toxicity profiles of the CARISSA trial of postoperative cisplatin-based chemoradiation ± gefitinib in head and neck cancer
Authors: J. Thariat, D. de Raucourt, P. Giraud, F. Peyrade, O. Dassonville, A. Cosmidis, G. Dolivet, G. Calais, J. Santini, R. Bensadoun
Journal: Journal of Clinical Oncology (2009)

e22152 Background: Concurrent cisplatin and postoperative irradiation (PORT) is the standard treatment for resected poor-risk squamous cell carcinoma of the head and neck (HNSCC) . However, a substantial number of patients fail to respond. Anti-EGFR agents, such as gefitinib, may improve outcomes and molecular markers might predict treatment efficacy. This was the basis for the CARISSA trial. There was some concern after hemorrhagic events occurred in a large independent trial of recurrent unresectable HNSCC. This caused a temporary interruption and safety profile analysis of CARISSA, which resumed after security reports showed no excess of hemorrhagic events. Methods: The CARISSA multicenter blinded randomized phase II trial compares PORT and cisplatin alone (arm A) or in combination with the EGFR Inhibitor ZD1839 gefitinib (arm B) in HNSCC and analyses EGFR-binding, gene polymorphisms, Western Blotting and immunohistochemistry. Patients are followed weekly. Toxicities are graded according to the NCI/CTCv.3 scale. Results: Thirty-eight patients have been included. Compliance to cisplatin was 56% in arm A and 44% in arm B (NS). Compliance to gefitinib was 60% with half cases interrupting treatment for toxicity. There were 18 and 20 grade (G) 3/4 non-hematological toxicities, 12 and 6 hematological G3/4 toxicities in arms A and B, respectively. Mucositis was the most common toxicity. G3 mucositis occurred in 4 and 5 cases in arms A and B, dermatitis in three cases in each arm and diarrhea in one case in each arm (NS). There were 7 cancer- related deaths and 3 of other causes. One tumor-bleeding event occurred in the arm without gefitinib. Full-dose radiotherapy was delivered in all but one case in each arm. Mean doses were 63.9 ± 1.9 (arm A) and 65.5 ± 0.9 Gy (arm B) or 64.7 ± 0.9 (arm A) and 65 ± 0.9 Gy (arm B) in groups where RT was uninterrupted or temporarily interrupted, respectively (NS). The two patients who did not receive full dose received 60 Gy. Conclusions: Compliance to PORT was similar with cisplatin alone or cisplatin + gefitinib. While there was no excess of hemorrhagic morbidity postoperatively (no gross disease), accrual continues with particular caution. No significant financial relationships to disclose.
ADAMs as new therapeutic targets for triple-negative breast cancer.
Authors: M. Mullooly, P. M. McGowan, S. U. Sukor, S. F. Madden, E. McDermott, J. Crown, N. O'Donovan, M. J. Duffy
Journal: Journal of Clinical Oncology (2011)

1062 Background: Triple negative breast cancers (TNBC) lack expression of ER, PR and HER2. Consequently, targeted therapy is currently unavailable for these patients. At least some TNBCs however, possess high levels of EGFR and are dependent on EGFR signaling. Activation of EGFR signaling is triggered by the release of ligands such as TGFα, EGF and HB-EGF. Release of these ligands is catalysed by the proteases, ADAM10 and ADAM17. The aim of this study was to test the hypothesis that inhibition of ADAM10/17 was a new approach for treating patients with TNBC. Methods: ADAM10 and 17 were measured at protein and mRNA levels in extracts of TN and non-TNBC. Pooled data from 22 published gene expression databases (N=approx 4,000 patients) was used to relate ADAM and ADAM17 mRNA to patient outcome. The effect of the dual ADAM10/17 inhibitor, GW280264X (GSK) on the proliferation of 7 TN and 6 non-TN breast cancer cell lines was investigated using the acid phosphatase assay and Calcusyn software. Results: Using extracts of breast cancer (n=185), the active form of ADAM17 was found in 98 % of TN and 95 % of non-TN samples. Importantly, significantly higher levels were present in TN than non-TN samples (p = 0.025, Mann Whitney U). Similarly, the active form of ADAM10 was detected in the majority (82%) of TN samples. Using pooled data from published datasets, high ADAM10 expression was associated with adverse prognosis in patients with basal-type (most of which were TN) breast cancer. Using the dual ADAM10/17 inhibitor GW280264X, we found up to 90 % reduction in cell growth (36 to 89 % growth reduction) across a panel of TNBC lines with IC50 concentrations ranging from 0.43 µM to 2.8 µM. In contrast, non TNBC lines responded with a range of 10 to 73 % growth inhibition and IC50 concentrations of 2.8 to >20 µM. Conclusions: Our results indicate that ADAM10 and 17 are expressed in the majority of TNBCs. Furthermore, ADAM inhibition resulted in impaired cell growth, migration and invasion of TNBC cells in vitro. Taken together, we propose that ADAM10 and ADAM17 may be novel targets for therapeutic intervention in TNBC. Authors PMcG and MM contributed equally to this work.
Antitumor activity of brentuximab vedotin in CD30 positive refractory germ cell tumors.
Authors: Costantine Albany, Darren Richard Feldman, Lawrence E. Garbo, Lawrence H. Einhorn
Journal: Journal of Clinical Oncology (2013)

327 Background: Brentuximab Vedotin (BV) is a novel antibody drug conjugate that combines the agent mono-methyl auristatin E (MMAE) to a CD-30 specific monoclonal antibody by a protease-cleavable linker. It is approved by the FDA for treatment of relapsed Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL). In addition to HL and ALCL, CD-30 expression has been reported on malignant tumors of non-lymphoid origin including testicular embryonal carcinoma (EC). Here we report our initial experience in three heavily pre-treated patients with CD30-positive EC who were treated as part of an ongoing phase 2 open-label multicenter study designed to evaluate the antitumor activity of BV in patients with CD30-positive non-lymphomatous malignancies. Methods: Three men with relapsed or refractory, histologically confirmed CD-30 positive testicular cancer received BV until progression or toxicity. CD-30 expression was assessed by immunohistochemistry. All 3 patients were dosed at 1.8 mg/kg IV every 21 days and followed for response at cycles 2, 4. Results: Three patients were enrolled at 2 sites in the US. Median age was 26 years (range 24-33). All 3 patients progressed after high dose chemotherapy with peripheral blood stem cell transplant. Two patients received BV as 4 th line and 1 patient as 3 rd line therapy. Tumor sites included lungs, liver, retroperitoneal, mediastinal and supraclavicular lymph nodes. The first patient baseline hCG was 5571. After 2 cycles of therapy, hCG nadir was 45 with a radiologic partial response (PR) by RESICT that lasted 2 months. He then had serologic and radiographic progression in the liver while on therapy. Patient 2 was serologic marker negative and had a radiographic PR by RECIST in lung and mediastinum after cycle 2 and continues on therapy. Patient 3 had a baseline hCG of 10400, with nadir at 110 after 2 doses and continues to have serologic response. By RECIST he currently has stable disease. The treatment was well tolerated in all 3 patients with no grade 3-4 toxicities. Conclusions: All 3 patients with heavily pretreated CD-30 positive EC had clinical benefit after treatment with brentuximab vedotin. The treatment was well tolerated. The enrollment is ongoing in this Phase 2 study. Clinical trial information: NCT01461538.
Abstract 17814: Prenatal Diagnosis is Associated with a Lower Rate of Pre-Operative Brain Injury in Newborns with Transposition of the Great Arteries
Authors: Shabnam Peyvandi, Veronica de Santiago, Patrick McQuillen
Journal: Circulation (2014)

Objective: Literature suggests that prenatal diagnosis of critical congenital heart disease does not lead to improved mortality. However, it has been associated with better pre-operative conditions in single ventricle lesions and better neurodevelopmental outcome in transposition of the great arteries (TGA). We sought to describe the frequency of pre-operative brain injury in neonates with prenatal and postnatal diagnosis of TGA. We hypothesize that prenatally diagnosed neonates with TGA have a lower prevalence of pre-operative brain injury. Methods: Term newborns with TGA were studied with brain magnetic resonance imaging preoperatively to determine brain injury severity based on the presence of white matter injury and/or stroke. Comparisons were made between prenatal and postnatal diagnosis. Other variables compared included estimated gestational age at birth (EGA), birth weight (BW), lowest oxygen saturation, balloon atrial septostomy (BAS), age at surgery, and hospital mortality. Analysis was performed with Fisher’s exact test or Student t-test. Further analysis will be performed including data from other centers and cardiac diagnoses. Results: The presence of brain injury was significantly higher in postnatally diagnosed neonates than those prenatally diagnosed (Table). There were trends toward lower EGA, lower BW, higher oxygen saturation and younger age at surgery in the prenatal group. BAS did not differ by prenatal diagnosis. Mortality was low and the only two deaths were in the postnatal group. Conclusions: Prenatally diagnosed neonates with TGA have a lower prevalence of preoperative brain injury as compared to those diagnosed postnatally. This finding is significant even when other known risk factors for brain injury did not differ between groups. Our data is consistent with prior literature demonstrating lower EGA and BW in prenatally diagnosed patients. The impact of these findings on neurodevelopmental outcomes will be studied.
Medulloblastoma models which harbor amplifications of myc family members are sensitive to BET-Bromodomain inhibition
Authors: Pratiti Bandopadhayay, Guillaume Bergthold, Brian Nguyen, Simone Schubert, Sharareh Gholamin, Yujie Tang, Sara Bolin, Steven Schumacher, Rhamy Zeid, Sabran Masoud, Furong Yu, Nujsaubnusi Vue, William Gibson, Brenton Paolella, Siddhartha Mitra, Samuel Cheshier, Jun Qi, Kun-Wei Liu, Robert Wechsler-Reya, William Weiss, Fredrik Johansson Swartling, Mark W. Kieran, James E. Bradner, Rameen Beroukhim, Yoon-Jae Cho
Journal: Neuro-Oncology (2014)

Medulloblastoma models which harbor amplifications of myc family members are sensitive to BET-Bromodomain inhibition
Long-term treatment of CTCL with the oral PNP inhibitor, forodesine
Authors: M. Duvic, A. Forero-Torres, F. Foss, E. Olsen, L. Pinter-Brown, Y. Kim
Journal: Journal of Clinical Oncology (2009)

8552 Background: Forodesine is a potent inhibitor of purine nucleoside phosphorylase (PNP) that leads to T-cell selective intracellular accumulation of dGTP, resulting in apoptosis. Methods: An open-label dose escalation study of oral forodesine (40–320 mg/m 2 daily) for 4 wks with extended therapy was performed to determine the maximum tolerated and/or optimal biologic dose (OBD). Additional subjects were accrued at an OBD (80 mg/m 2 ) to further assess safety and clinical efficacy. Subjects with refractory CTCL, stages IB-IV were eligible. The primary efficacy endpoint (objective response rate [ORR]) was defined as ≥ 50% improvement by a severity-weighted assessment tool (mSWAT). Results: The overall intent to treat response rate was 17 of 64 (27%) subjects or 14 of 36 (39%) at the OBD. As of October 2008, nine of 64 subjects (14%) have received forodesine treatment for &gt;12 months. This cohort of 9 subjects is further examined. Six discontinued treatment (median time on treatment 440 days): 4 for progressive disease, 1 withdrew consent, and 1 due to an adverse event (Diffuse Large B-cell Lymphoma). Three are continuing on therapy for 416, 710, and 863 days. Median age was 68 years (range 42, 81), and all but one was ≥ stage III. They had received a median of 3 prior systemic therapies including 8 of 9 with prior bexarotene. Five of 9 subjects had a response (2 with complete response, 3 with partial response, and 4 with stable disease). Related AEs were experienced by 7 of 9 subjects. The most frequent were nausea (44%), fatigue, peripheral edema, dyspnea, and urinary casts (all 22%). Grade 3 or higher related AEs were experienced by 2 of 9 subjects (Diffuse Large B-Cell Lymphoma as previously mentioned and peripheral edema). There were no hematologic or infection AEs related to forodesine. Grade 3 lymphopenia and CD4 count &lt; 200 were noted in 8 of 9 and 4 of 9 subjects respectively. The risk of any infection AE regardless of cause in these 9 subjects was 15 per 100 person-months of forodesine exposure compared to 59 in all other subjects (n=55). Conclusions: Forodesine has an acceptable safety profile and efficacy in these CTCL subjects treated for 12 months or longer. [Table: see text]
First-in-human dose-escalation safety and PK trial of a novel intravenous humanized monoclonal CovX body inhibiting angiopoietin 2.
Authors: L. S. Rosen, D. S. Mendelson, R. B. Cohen, M. S. Gordon, J. W. Goldman, I. K. Bear, B. Byrnes, R. Perea, S. L. Schoenfeld, A. Gollerkeri
Journal: Journal of Clinical Oncology (2010)

2524 Background: CVX-060 is a recombinant humanized monoclonal antibody fused to two angiopoietin-2 (Ang2) binding peptides. In preclinical studies, CVX-060 is antiangiogenic and decreases tumor proliferation. Methods: In stage 1, pts with solid tumors received escalating doses of CVX-060 in cohorts of 3-6 pts at the following doses: 0.3, 1, 3, 6, 12, or 15 mg/kg. An additional 13 pts were treated at the 15 mg/kg dose in stage 2. CVX-060 was given once weekly in 4 week cycles as a 90 min IV infusion, decreased to 30 min as tolerated. DLTs were defined as ≥ Gr 3 AEs unrelated to tumor progression in cycle 1. Serum PK was assessed by ELISA. DCE-MRI were conducted pre- dose, Day 4, and Day 28, in pts at 3 mg/kg and higher. Results: Complete data are available on 30 of 34 pts who were enrolled in the study. Among the 30 pts (19F/11M), the median age was 65 years (21-90), ECOG performance status 0-1. Drug exposure in pts ranged from 6-407 days (median 49 days). One pt in the 0.3 mg/kg cohort experienced a DLT (Gr 3 back pain). The most common AE was fatigue (23%).The MTD was not defined. There were 5 (17%) pts with proteinuria (one with Gr 3 and the rest Gr 1-2) and 2 (7%) pts with Gr 1 hemorrhage (vaginal spotting). Cmax and AUC increased linearly with dose, with mean ß t1/2 of 5.5 days. Total serum Ang2 (bound plus free) increased with escalating doses, plateauing at 15 mg/kg. Patients with the highest baseline Ang2 levels had the highest increases in total Ang2 after treatment. There were significant mean decreases in Ktrans by DCE-MRI at Day 4 (p=0.034) and Day 28 (p=0.0025) in 11 pts with data available at all 3 time points. 10/11 patients had decreases in Ktranswith mean decreases of 12.9% (0.94%- 44%) at Day 4 and 25.6% (8-61%) at Day 28. Of the 34 patients enrolled, 24 (71%) remained on study ≥8 weeks and 4 patients continue on treatment (maximum of 17+ months in a patient with refractory cervical cancer). Based on the PK/PD analysis, 15 mg/kg is the recommended phase II dose. Conclusions: CVX-060 is a well-tolerated novel therapy targeting angiogenesis. PK results support once-weekly dosing. There is preliminary evidence of biological activity based on DCE-MRI and prolonged stable disease. A combination trial with sunitinib is underway. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Data Safety Committee for non-oncology compound Pfizer
A pilot study of the effect of exposure to child abuse or neglect on adolescent suicidal behavior
Authors: E Y Deykin, J J Alpert, J J McNamarra
Journal: American Journal of Psychiatry (1985)

The authors designed a pilot study to test if exposure to child abuse or neglect is associated with suicidal behavior in adolescence. Each of 159 adolescents who had attempted suicide was age- and sex-matched with two comparison subjects who had been treated for medical conditions unrelated to suicide attempts. The registry of the Massachusetts Department of Social Services was searched for the names of the subjects and comparison subjects. For both sexes prior contact with the Department of Social Services was three to six times more likely for probands than for the comparison subjects.
Premature deaths and severe morbidity in 192 long-term survivors of pediatric optic pathway tumors (OPT): A 50-year study.
Authors: E. De Carli, C. Kalifa, M. Raquin, J. Lemerle, J. Habrand, D. Couanet, C. Sainte-Rose, X. Rialland, D. Valteau-Couanet, J. Grill
Journal: Journal of Clinical Oncology (2010)

9555 Background: The natural history of OPT remains unpredictible and optimal therapeutic management is still controversial. Long-term follow- up is mandatory to judge the survival and the morbidity of these patients. Methods: The study describes the outcome of a large single institution cohort treated for an OPT between 1952 and 2004, with at least 5 years of follow-up of the survivors, two third being treated with radiotherapy during the course of their disease. Results: With a median follow-up of 12 years, 5, 10, 20 and 30 years overall survival (OS) were 90%, 83%, 70% and 56%, respectively. Mortality was higher in children younger than 1 year at diagnosis but was not influenced by treatment. Among children receiving chemotherapy, survival was better in case of radiological response to treatment ; 10y OS was 90% vs 66% (p=0.017). Main causes of the 57 deaths were progression of the tumor (27) and second tumors (11), both ocurring eventually late during follow-up. Second tumors were more frequent in children receiving irradiation (p=0.008), especially before the age of 6 (p=0.008) and/or in the context of NF1 (p=0.003). Visual outcome was poor ; 35 (20%) complete and 73 (40%) monocular blindness. It was poorer in younger children (p=0.05) but was not associated with the type of treatment. Vascular complications (p=0.08), epilepsy (p=0.002), neurocognitive impairment (p<10e4), and GH deficiency (p<10e4) were more frequent in children receiving irradiation. Hemiplegia found in 21 patients was due to tumor in 10 or to stroke in 11. Early puberty was described in 51 (26%) patients and was more frequent in children younger at diagnosis (32% vs 21%, p=0.008). Diabetus insipidus was more frequent after surgery (p=0.01). Obesity noted in 46 (34%) was not linked to surgery, nor to the initial presentation with diencephalic syndrome. Young children and NF1 patients had more frequently school delays than the others (p=0.04 and p=0.005, respectively). Conclusions: In children with optic pathway tumors, morbidity is severe, especially after irradiation. Long-term multidisciplinary surveillance is mandatory in order to decrease preventable deaths. Refinement of therapeutic strategies is definitively needed. No significant financial relationships to disclose.