tbuckley/cabot-search huggingface dataset:
Association of gene expression signature and clinical efficacy of MAGE-A3 antigen-specific cancer immunotherapeutic (ASCI) as adjuvant therapy in resected stage IB/II non-small cell lung cancer (NSCLC)
Authors: J. F. Vansteenkiste, M. Zielinski, I. J. Dahabreh, A. Linder, F. Lehmann, O. Gruselle, P. Therasse, J. Louahed, V. G. Brichard
Journal: Journal of Clinical Oncology (2008)

7501 Background: A phase II randomized trial in 182 patients (pts) with completely resected stage IB or II MAGE-A3 (+) NSCLC comparing postoperative MAGE-A3 recombinant protein combined with an Adjuvant System to placebo (q3w x 5, followed by q3m x 8) showed a strong positive signal for activity (J Clin Oncol 25 Suppl 18:398S, 2007). We report here the analysis of gene expression profiling of tumors prior to treatment to identify a predictive signature that correlates with clinical activity of MAGE-A3 ASCI treatment. Methods: Microarray analysis (Affymetrix) was performed on 159 fresh-frozen tumor biopsies (MAGE-A3: 108; placebo: 51; stage IB: 109; stage II: 50). Clinical data on relapse are based on a median follow-up of 44 months. Results: Study of tumor samples from pts in the placebo arm led to identification of a gene signature associated with a high risk of postoperative relapse. The absence of this signature correlated with a very low relapse rate in stage IB pts: placebo 0%; MAGE-A3: 4%. In the MAGE-A3 treated pts with the high risk of relapse signature, we compared 10 biopsies from stage IB pts with recurrence to 10 pts without recurrence. A 25 regulated gene probe predicted benefit from MAGE-A3 treatment. The relevance of this signature was confirmed on the remaining 139 stage IB and II biopsies. The predictive signature improved clinical efficacy (disease-free interval) (HR in GP+: 0.57; HR in GP-: 0.78) with no impact on relapse rate in the placebo arm. The signature consisted of immune- related genes associated to the pre-therapeutic tumor microenvironment. Conclusions: We identified a gene expression signature associated with high risk of relapse. Pts with tumors not presenting this signature have a very low risk of relapse after surgery (<3%). We also described another signature that is predictive to clinical activity of the MAGE-A3 ASCI treatment. Selection of pts with this predictive signature increases clinical efficiency by a factor 2. Interestingly, this signature is also associated to clinical activity to MAGE-A3 in a study in metastatic melanoma. Data will be validated in the ongoing NSCLC adjuvant phase III study (MAGRIT). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline
Pharmacokinetic (PK) profile of a single dose of everolimus (10 mg) administered with a low- or high-fat meal and under fasting conditions in healthy subjects.
Authors: W. Cheung, C. Ligia, A. Jappe, O. Anak
Journal: Journal of Clinical Oncology (2011)

e15080 Background: The mTOR inhibitor everolimus is approved for patients (pts) with metastatic renal cell carcinoma after failure of sunitinib or sorafenib, and for pts with subependymal giant-cell astrocytoma associated with tuberous sclerosis who require therapeutic intervention but are not candidates for curative surgery. Studies in healthy subjects suggest that systemic exposure to everolimus is reduced with a high-fat meal. The effect of fasting conditions and food on everolimus PK after an oral 10 mg dose was evaluated. Methods: In this single-center, open-label study, 24 healthy male and female subjects were randomized to single doses of everolimus in a 3-treatment (low-fat vs high-fat meal vs fasting), 3-period, 6-sequence crossover design. Treatment periods were separated by 14-day washout intervals. PK was assessed at baseline and at 0-12, 24, 36, 48, 72, 96, 120, and 144 hours postdose. Results: All 24 subjects were included in the PK analysis. The geometric mean Cmax decreased by 42% after a low-fat meal and by 54% after a high-fat meal compared with fasting conditions. Total exposure (geometric mean AUC0-t and AUC0-∞) decreased by 22% to 33% after intake of a low- or high-fat meal. A meal had no apparent effect on the post-absorption concentration-time profile. The gastrointestinal absorption rate of everolimus was decreased by food intake: median Tmax was 1 hour in the fasted state, 1.75 hours after a low-fat meal, and 2.50 hours after a high-fat meal. The elimination kinetics in whole blood (T1/2 [35.6 to 40.9 hours] and mean residence time [29.2 to 32.2 hours]) did not appear to be affected by food intake regardless of fasting or nonfasting state. No deaths, serious adverse events (AEs), or significant AEs were reported. Conclusions: The systemic availability of a single oral 10 mg dose of everolimus is significantly reduced by coadministration with a meal (low or high fat) compared with fasting conditions; however, food is not expected to have clinically significant effects on predose trough concentration during daily administration of everolimus. All conditions tested were safe and well tolerated.
Use of clinical care registries to facilitate research study recruitment.
Authors: Karen Messer, Tracy M. Layton, Tony Chen, Viswanath Nandigam, Katherine Abihider, Peter W. Chase, John P. Pierce, Lisa Madlensky, Lisa Cadmus, Ruth E. Patterson, Susan Faerber, Richard B. Schwab, Sarah Blair, Anne M. Wallace, Haydee Ojeda-Fournier, Barbara A. Parker
Journal: Journal of Clinical Oncology (2013)

129 Background: We developed IRB-approved secure research registries for our Breast Imaging and Breast Care Clinics at Moores UC San Diego Cancer Center, as part of the UC statewide Athena Breast Health Network. Our clinical care registries securely store patient-reported intake data, which are summarized and uploaded into the medical record for patient care. Following consent, data are securely maintained in a separate research registry. In addition to facilitating quality assurance data collection, these registries aim to 1) maintain a data-rich research registry, 2) offer patients research opportunities, and 3) facilitate participant screening and recruitment into research studies. Methods: Breast Imaging or Breast Care clinic patients complete an online clinical intake form prior to their appointment, either at home or using an iPad in clinic, and are given the opportunity to be involved in research. Patients are asked for site-specific consent to keep personally identifiable intake data in a research registry, for consent to be approached about providing a biospecimen sample, and for consent to be contacted for future research opportunities. Data from consented participants are pulled into secure databases available to study personnel. Results: Participants to date include 4,480 patients, of whom 3,246 consented to use of data for research (72%), and 2,627 have agreed to be contacted for future research opportunities (59%). In a pilot biospecimen collection protocol, 46% of patients agreed to be approached and we have collected over 360 blood or saliva and 51 tissue samples. Additionally, with the use of future contact consent, we have facilitated recruitment of more than 370 participants to multiple lifestyle and survey-based clinical studies. Conclusions: Patients are willing to participate in research, especially in a research registry that requires little additional time on their part. The use of research registries allows collection of a variety of data elements useful for prescreening participants for research studies, including body mass index, age, menopausal status and breast cancer diagnosis. Data- and participant-rich research registries facilitate efficient screening and recruitment for other research studies.
Compassionate treatment (CTr) with re-irradiation, carboplatin (Cb) and Cetuximab (C) in very advanced head and neck cancer (HNC)
Authors: G. Numico, I. Colantonio, A. Heouaine, M. Occelli, E. Fea, E. G. Russi, R. Vigna Taglianti, L. Lanzillotta, M. C. Merlano
Journal: Journal of Clinical Oncology (2006)

13153 Background: Extremely locally advanced HNC is a dramatic clinical situation, causing pain, repeated infections, speech and swallowing impairmen, malnutrition and cosmetic disasters. Re-irradiation may partially palliate some pt, but the low dose of radiation that can safely be delivered limits this approach. Recently the combination of C and radiation has shown improvement of clinical outcome over radiation alone. Methods: We started a CTr with re-irradiation concurrent with Cb and C in pts with heavily symptomatic, pretreated HNC. CTr consisted of: RT (30 Gy) 2 Gy/d, 5 d/week given every other week; Cb AUC 6 d 1, 22 and 43; C, 400 mg/m 2 loading dose and 250 mg/m 2 maintenance, weekly until day 43 (6 administrations). Results: From January 04 to June 05, 8 pts pre-treated with surgery (6 pts), radiation (8) and chemotherapy (6) entered the CTr. All pts but one had bulky soft tissue invasion and 2 had skin ulceration. One had only bulky nodal relapse. One pt died after the 2 nd week due to pneumonia. The other pts had a fast response to CTr: within 5–7 d from the start of therapy they reached a clinical benefit (major or complete pain relief, improvement of swallowing and/or neck movements) and subsequently a rapid tumor shrinkment. All pts achieved an objective response (complete response in 2). No significant local or systemic toxicity occurred in any of the pts, but a mild skin rush. The first 4 pts did not receive further treatment after CTr. These pts showed tumor re-growth within 4–6 weeks from the end of treatment. However one of them underwent salvage surgery and is alive and disease free 14 months after CTr. The 3 other pts received maintenance treatment with weekly C until disease progression. One of them died due to cancer unrelated causes without PD 11 weeks after RT. The 2 nd pt developed PD during RT. The 3 rd pt is progression-free and alive at 30 weeks from the end of RT. Overall, TTP of the 7 pts ranges between 2 and 7+ months (median 3); survival from the end of RT ranges between 3 and 14+ months (median 7+). Conclusions: CTr with re-irradiation, Cb and C seems feasible even in this poor prognosis, very advanced HNC. No additional toxicity was recorded by adding C. Palliation was achieved in almost all pts and the results deserve further investigations. No significant financial relationships to disclose.
Abstract 12803: Galectin-3 is a Prognostic Biomarker for Patients After Transcatheter Aortic Valve Implantation
Authors: Gerd Baldenhofer, Sebastian Spethmann, Michael Laule, Bjoern Eilers, Wasiem Sanad, Henryk Dreger, Gert Baumann, Karl Stangl, Verena Stangl, Fabian Knebel
Journal: Circulation (2014)

Introduction: Until now, a reliable biomarker to predict the short- or long-term outcome for patients undergoing TAVI is still missing. Galectin-3, a novel marker indicative for myocardial fibrosis, has prognostic value in heart failure. Our goal was to investigate whether galectin-3 is suited for risk assessment in TAVI patients. Methods: We included 101 patients undergoing TAVI in this prospective, single-center, observational study. Baseline galectin-3 levels were correlated to the VARC 30-day safety and one-year efficacy endpoint as well as to total mortality and cardiovascular events at one year. Results: The VARC 30-day safety endpoint was reached by 24 patients. At one year, 43 patients met the VARC efficacy endpoint, 16 patients died, and 23 cardiovascular events were recorded. At baseline, mean galectin-3 level for the entire group was 18.1 (± 11.1) ng/ml. Of the 101 patients, 36 had a galectin-3 value above the cut-off value of 17.8 ng/ml. These patients had significantly higher systolic pulmonary artery and capillary wedge pressures. The hazard ratio in patients with galectin-3 &gt; 17.8 ng/ml was 3.36 (95 % confidence interval, CI: 1.47 - 7.69; p = 0.004) for the VARC 30-day safety endpoint, 5.12 (95 % CI: 2.10 - 12.47; p &lt; 0.001) for one-year cardiovascular events, and 4.48 (95 % CI: 1.56 - 12.91; p = 0.005) for all-cause mortality. This prediction remained stable even after adjusting for possible confounders including age, sex, glomerular filtration rate, and NT-proBNP. Furthermore, the prediction was even more valuable when combining galectin-3 with NT-proBNP for cardiovascular events (HR = 6.39; CI: 2.87-23.89; p &lt; 0.001) and all-cause mortality (HR = 8.28; CI: 2.01-23.59; p &lt; 0.001). Conclusions: Elevated galectin-3 levels are independently associated with adverse outcome after TAVI. Combining galectin-3 with NT-proBNP provides additive predictive value of risk stratification.
Phase II trial of pegylated liposomal doxorubicin as consolidation chemotherapy in patients with stage III or IV ovarian or primary peritoneal carcinoma
Authors: P. A. Disilvestro, M. Fisher, M. Pearl, F. Valea, A. Buhl, E. Chalas
Journal: Journal of Clinical Oncology (2004)

5112 Background: Patients with stage III and IV cancer of the ovary and peritoneum are commonly treated with a combination chemotherapy involving a taxane and a platinum agent after surgical debulking. Data has recently been presented supporting the role of consolidation chemotherapy at the conclusion of first line treatment, potentially prolonging disease free survival. This phase II trial investigated the use of pegylated liposomal doxorubicin (Doxil/Caelyx) as consolidation therapy. Methods: Women with stage III or IV ovarian or primary peritoneal carcinoma demonstrating no clinical evidence of disease at the conclusion of six cycles of primary taxane and platinum chemotherapy were eligible for enrollment. Patients received 4 cycles of 40 mg/m2 IV of pegylated liposomal doxorubicin every 28 days. Results: Twelve patients have been enrolled and 11 patients have completed therapy. The mean age of patients was 55. Eleven patients had ovarian cancer, 1 patient had primary peritoneal cancer. Six patients were stage IIIC and 6 were stage IV. Four patients had 3 cycles of neoadjuvant chemotherapy as part of their primary regimen. Of the 8 patients primarily explored, 7 were optimally cytoreduced. Of the 11 patients who have completed therapy, nine received the prescribed four cycles. Two patients had dose limiting skin toxicity and received only three cycles. Of those who completed 4 cycles, two required a dose reduction after 3 cycles. With a median follow-up of 22 months, mean disease free survival for the first dose of pegylated liposomal doxorubicin to last contact is 14 months. Six patients are disease free, 4 patients have relapsed and one patient has died from disease progression Conclusions: Based on this small preliminary set of data, pegylated liposomal doxorubicin appears to be a well tolerated choice for consolidation chemotherapy. The majority completed the prescribed treatment with few toxicities. Preliminary disease free survival is encouraging given that a number of patients with suboptimal disease at initial presentation were entered. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho Biotech Pharmaceuticals
A phase I and pharmacokinetic study of HGS-ETR1(TRM-1), a human monoclonal agonist-antibody to TRAIL R1, in patients with advanced solid tumors
Authors: A. W. Tolcher, M. Mita, A. Patnaik, E. K. Rowinsky, A. Corey, M. Fleming, N. L. Fox, L. M. Weiner, N. J. Meropol, R. Cohen
Journal: Journal of Clinical Oncology (2004)

3060 Background: HGS-ETR1 (TRM-1) is a fully-human high affinity monoclonal antibody directed and agonistic to the Tumor Necrosis Apoptosis Inducing Ligand (TRAIL) Receptor 1. TRAIL R1 is widely expressed on human tumor cells, is part of the tumor necrosis factor superfamily, and regulates the activation of caspases in the extrinsic pathway of apoptosis. TRM-1 mediates apoptosis via binding with TRAIL R1 and agonist induced activation of the extrinsic pathway of apoptosis. In preclinical studies TRM-1 induces apoptosis in sensitive human tumor cell lines in vitro at an IC50 of 3.3 nM and elicited both tumor growth inhibition and tumor regressions in a broad array of human tumor xenograft models at 10 mg/kg. Methods: Patients with advanced refractory solid tumors were treated with TRM-1 iv once every 28 days. Results: Currently 31 patients have received 56 courses of TRM-1 over 6 dose levels that ranged from 0.01 to 3.0 mg/kg. The median number of courses is 1 (1–6). One patient with pre-existing grade 2 peripheral neuropathy treated at the first dose-level had worsening of symptoms to grade 3, although no other patient has had drug-related toxicities ≥ grade 2. Pharmacokinetic parameters (Mean [±SD] ) at the 1 mg/kg dose level are characterized by a long elimination t1/2 of 14.4 [4.9] days, Vd that approximates plasma volume, Cl of 3.8 [1.4] mL/day/kg, Cmax of 23.6 [5.1] μg/mL, and an AUC of 290.4 [97.2] μg × days/mL. No evidence of human anti-human antibody formation has been detected. Accrual continues next at the10 mg/kg dose level. Conclusions: TRM-1 represents the first specific TRAIL R1 targeting agent and can be safely administered IV every 4 weeks at doses that reach plasma concentrations associated with activity in preclinical studies. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Human Genome Sciences Human Genome Sciences Human Genome Sciences Human Genome Sciences Human Genome Sciences
Dose-dense epirubicin with paclitaxel as preoperative treatment in locally advanced breast cancer: Phase II trial
Authors: Y. L. Bautista Aragón, J. Silva, G. Gonzalez Avila, A. Gutierrez, M. Pluma-Jiménez
Journal: Journal of Clinical Oncology (2009)

e11633 Background: Treatment of locally advanced breast cancer (LABC) with anthracycline-based regimens have pathological complete response (pCR) of 10–15%, and with anthracyclin-taxane therapy have pCR 18–30%. Combined or sequential are both acceptable with the most important agents. Methods: We use a dose- dense regimen epirubicin and paclitaxel for 12 weeks to determine the effectiveness in the neoadjuvant setting could increase pCR and safety of the regimen. This phase II study investigated women with untreated locally advanced breast cancer assigned to receive epirrubicina 25 mg/m2 and paclitaxel 70 mg/m2 for twelve weeks. Results: 21 patients were enrolled at median follow up of eight months. The median age was 55 years old (28–67). The distribution by TNM was IIB (15%), IIIA (52%), IIIB (24%) y IIIC (9%) and tumor type was lobular (24%) and ductal (76%). The mean tumor size was 8 cm (5 -14 cm). Ninety percent completed twelve cycles of chemotherapy with a two hundred forty five cycles administered. In six patients had dose reduction by 10–20% in subsequent doses and one patient withdrawn from de study because of chemotherapy related toxicity. In 9 percent of patients we use G-SCF. Surgery was performed in 18 patients. Eleven patients (52%) achieved a clinical response (PR o CR) after twelve cycles. Complete pathological response and partial was 11% y 14%. Subset analysis of the effect of Independent predictors included receptor status, Her2 neu, tumor size, and histology was no statistically significant (p.68). Treatment was generally well tolerated. Grade 3/4 non-hematologic adverse events (neurotoxicity, nauseas and palmar plantar dysesthesia) events occurred in 5% of patients. No cardiac toxicity was found. Conclusions: Despite the small sample size, it was representative of our population of LABC. These data indicate that the combined regimen in dose-dense epirubicin and paclitaxel is a regimen with acceptable toxicity. However we have low percent of cPR, maybe we have a high percent of patients with stage IIIA and IIIB with large diameter of tumor size. No significant financial relationships to disclose.
Imatinib treatment for patients with advanced stage hepatocellular carcinoma: A multicenter phase II trial.
Authors: I. W. Graziadei, A. Finkenstedt, R. Stauber, M. Trauner, C. Mueller, W. Vogel
Journal: Journal of Clinical Oncology (2010)

e14629 Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with limited treatment options in advanced stages. The antitumor activity of systemic chemotherapies in patients with HCC has been disappointing. The aim of this study was to evaluate the safety and efficacy of imatinib, a tyrosine kinase inhibitor, in patients with advanced HCC. Methods: Patients with stage III and IVa/b HCCs without surgical and/or loco ablative therapeutic options and preserved liver function (CPC A/B) were eligible. The patients were treated with 400 mg imatinib daily for 12 months. Response was assessed by CT scan. Results: 22 patients (5 f, 16 m; mean age 67) were enrolled in this study. The causes of liver disease were mainly viral (5) and (non) alcoholic fatty liver disease (8). 15 patients presented with CPC A and 3 with B, 3 patients had no evidence of liver cirrhosis. 14 patients had had previous HCC-treatments, mainly resection or loco ablative therapies. Patients were treated with imatinib for a median time period of 9 (4-52) weeks; in 10 patients imatinib was discontinued due to tumor progression, in 4 due to the patients' decision, in 2 due to decompensated liver cirrhosis and in one due to pruritus; 4 patients received the drug for the intended 12 months. Median TTP was 12 (95%CI: 10-14) weeks. Two patients (HCC in noncirrhotic liver) had stable disease throughout the study period, one until discontinuation (pruritus) and the remaining 18 patients developed disease progression. The median overall survival was 7.4 (95%CI: 5.9-8.9) months. Complications due to decompensated liver cirrhosis were the causes of death in all patients. No severe adverse event related to imatinib was observed; the most common adverse events were nausea (10) and peripheral edema (8). In 4 patients imatinib dosage had to be reduced to 200 mg daily after 2, 4, 14 and 28 weeks of treatment because of nausea (3) and angioedema (1). Conclusions: The results of this multicenter study suggest that imatinib is well tolerated in the majority of HCC patients. The median TTP was 11 weeks which is comparable to other targeted therapies indicating that imatinib might be a promising candidate for further studies in the treatment of advanced HCC. No significant financial relationships to disclose.