tbuckley/cabot-search huggingface dataset:
Phase II trial of interferon-beta-serine in metastatic renal cell carcinoma.
Authors: P Kinney, P Triozzi, D Young, J Drago, B Behrens, H Wise, J J Rinehart
Journal: Journal of Clinical Oncology (1990)

Interferon-beta-serine (IFN-beta-ser) is a muteine, recombinant IFN that is tolerated at a dose fivefold to 10-fold higher than IFN-alfa and interacts with the same cell membrane receptor as IFN-alfa. We hypothesized that at high doses IFN-beta-ser might induce a higher response rate than IFN-alfa in metastatic renal cell carcinoma. We undertook a phase II trial of IFN-beta-ser in patients with metastatic renal cell carcinoma. Patients were treated three times each week by a 2-hour intravenous infusion. Doses were escalated weekly (.25 to 5.5 mg, 1 mg = 180,000,000 U) until the maximum-tolerated treatment dose (MTTD) was determined. The MTTD is defined as one dose level less than that which caused grade 3 toxicity and was subsequently administered three times weekly for at least 4 weeks. Twenty-nine patients were entered, and 25 were assessable for response and toxicity. The performance status was 0-1 in all patients and only one patient received previous chemotherapy. The MTTD dose was 2.5 mg (range, 0.5 to 5.5 mg per treatment), although in 10 patients, doses were later deescalated because of cumulative toxicity. Initial dose-limiting toxicity and cumulative toxicity were fatigue, malaise, and fever in most patients. Hepatic transaminitis, neutropenia, and elevation of serum creatinine were also observed but were not dose-limiting. There was one complete response (CR) and four partial responses (PRs). All responses but one occurred in pulmonary metastases. The median time to response was 26 days (range, 17 to 102 days). These data demonstrate that IFN-beta-ser given in high doses exhibits significant antitumor activity in renal cell carcinoma; however, the objective response rate is 20%. This is no higher than previous IFN studies; therefore, we reject the hypothesis than IFN-beta-ser at high doses may induce a greater response rate than IFN-alfa. However, we did observe more responses than were seen in a similar trial undertaken with lower dose IFN-beta serine in renal cell carcinoma.
A phase I/II trial of DTIC and dasatinib in metastatic melanoma.
Authors: A. P. Algazi, J. S. Weber, S. Andrews, P. Urbas, E. Arimura, J. Hwang, V. K. Sondak, B. Bastian, A. Daud
Journal: Journal of Clinical Oncology (2010)

8532 Background: Activation of the SRC-Stat pathway is present in melanoma and Stat3 activation is present in a large proportion of melanoma cell lines and human metastatic melanoma tumors. In preclinical models, SRC inhibitors can sensitize cancer cell lines to chemotherapy agents. We tested the hypothesis that dasatinib may increase the effectiveness of DTIC chemotherapy for melanoma. Methods: We conducted a prospective phase I/II trial of dasatinib combined with DTIC in patients with unresectable metastatic melanoma. Patients had an ECOG PS 0-1, normal organ function and cutaneous, mucosal or ocular melanoma. DTIC was administered on the first day of each 21-day cycle with dasatinib given on treatment days 2 through 19. In the phase I portion of the trial, dasatinib and DTIC were escalated starting from 50 mg BID of dasatinib with DTIC at 800 mg/m2. Tumor blocks were obtained for IHC/mutation analysis. Results: The maximum tolerated dose of dasatinib was 70 BID or 100 mg QD when given with DTIC at 1,000 mg/m2 at this schedule. Dose limiting toxicity and major grade ¾ toxicity was hematological with thrombocytopenia and neutropenia. Edema, pleural effusions and GI toxicities were infrequent. Of 49 patients treated in this trial, four (8.2%) had partial tumor responses by RECIST criteria, 25 (51.0%) had prolonged stabilization of disease, 15 (30.6%) had disease progression as the best treatment response, and five patients were either unevaluable or data are pending. The rate of clinical benefit (CR+PR+SD) was 59.2%. The median progression-free survival was 13.1 weeks and the median overall survival was 34.4 weeks. We are currently analyzing pSRC and SRC levels as well as B- RAF and c-kit mutation status in paraffin embedded tissue blocks to identify markers of response. Conclusions: The maximum tolerated dose of dasatinib is 70 mg BID or 100 mg QD when given on a day 2-19 cycle with DTIC at 1,000 mg/m2. The most common toxicities were hematological, especially thrombocytopenia and neutropenia. This combination appears to be associated with is associated with a high level of clinical benefit and a median PFS that compares favorably to historical controls, and, thus, it warrants further study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb
I131-tositumomab monotherapy as frontline treatment for follicular lymphoma: Updated results after a median follow-up of 8 years
Authors: M. S. Kaminski, J. Estes, M. Tuck, C. W. Ross, R. L. Wahl
Journal: Journal of Clinical Oncology (2007)

8033 Background: Monoclonal antibody-based therapies are improving the outcome for patients (pts) with follicular lymphoma (FL). Radioimmunotherapy has been found to be effective for pts with relapsed/refractory disease, but even more so when used as frontline treatment. Methods and Results. We previously reported the results of a phase II, single-institution, study of anti-CD20 I-131- Tositumomab (Bexxar) given as a single agent and as a single one-week treatment for 76 pts with Stage 3 or 4 FL (NEJM 352:441, 2005). An overall response (OR) rate and complete remission (CR) rate of 95% and 75%, respectively, were observed. With a median follow-up of 5.1 yrs, 5-yr overall survival (OS) and progression-free survival (PFS) were 89% and 59%, respectively, with a median PFS reached at 6.1 yrs. We now report on this pt cohort after a median follow-up of 7.93 yrs. The 8-year and 10-yr OS is estimated (by KM) now at 86% and 8-yr PFS is 50% (95% CI: 38.8 - 61.7%). Only 3 additional relapses have occurred in the additional follow-up period (at 8.0, 8.3, and 9.2 years) in those with CRs. The 8-yr PFS for the 57 pts who achieved CR is now 64%. The median for PFS has now being reached for CRs at 9.2 yrs. When the impact of baseline FLIPI scores were analyzed, only 8-yr OS was significantly affected when low-risk (LR) and intermediate-risk (IR) categories were combined and compared to the high-risk (HR) category (92% vs. 75%; p = 0.029). The 8-yr PFS for LR + IR pts was 56% vs. 35% for HR pts (p = 0.317). 27 of the 76 total pts (35%) had HR scores. Of additional importance, no cases of MDS or AML have yet been observed. Other longterm toxicities including thyroid status and second non-hematologic cancers will be updated at the meeting. Conclusions. These data underscore the high degree of effectiveness and durability of remissions achieved with a single, one-week course of frontline Bexxar and should serve as a benchmark for comparison to other studies using more prolonged and toxic treatments, including those combining unlabeled or radiolabeled antibodies with chemotherapy. No significant financial relationships to disclose.
Usefulness of BAL in non-HIV inmunocompromised hosts with lung infiltrates
Authors: Alejandro Raimondi, Ignacio Bledel, Vujacich Patricia, Berenger Roxana, Diaz Mariano, Carlos M. Luna, Gigliotti Romina
Journal: European Respiratory Journal (2014)

Introduction: Infectious and non-infectious pulmonary complications are an important cause of morbidity and mortality in non-HIV immunocompromised patients. Lung infiltrates in this group of patients includes an extensive list of possible causes. An etiological diagnosis obtained as soon as possible is essential to guide a specific therapy.  Aims and objectives: Evaluate the usefulness of BAL in non-HIV patients with lung infiltrates to determine etiology and changes in therapeutic decisions.  Methods: we prospectively included all those non-HIV immunocompromised patients with lung infiltrates who were evaluated by the Pulmonary Division to perform a BAL. The attending physicians were responsible for the diagnostic and therapeutic decisions.  Results: 57 patients were included and in 38 (66.7%) an etiological diagnosis was found (table 1). In 40 patients (70%) BAL resulted in a change of therapeutic decisions. There was a greater change of decisions when BAL was performed during the first 12 hours of initiation of empirical antibiotic therapy (p = 0.03)  Conclusions: BAL was useful for changing therapeutic decisions, especially when it was performed in the first 12 hours of treatment.
Mycobacterium abscessus diagnosed in hemoculture
Authors: Ersan Atahan, Benan Musellim, Hakan Kalyoncu, Gökhan Aygun
Journal: European Respiratory Journal (2013)

A 23 y/o female admitted with complaints of fewer, dyspnea, and cough for a month. She was diagnosed systemic lupus erytematotus (SLE) at 2006 and taking prednisolone and azothiopurin medication. Alveolar hemorrage had been developed once during 6 years follow up. Bilateral alveolar opacities were seen on chest X-ray, Sputum AFB staining was negative and meropenem + trimetoprim/sulfametaxazol were administered emprically. Leucocyte ;2300 /mm 3 , hemoglobin: 7.9 g/dl, ESR: 89 mm/h, CRP: 121. pO2 was 61 mmHg; remaining biochemical parameters were normal. Mediastinal, hilar subcarinal conglomerated lymphadenomegaly and extensive interlobular septal thickening and ground glass opacities were seen bilateral lung parenchima on Thorax CT. Gram (+) bacili growed on hemoculture. Linesolid and amicacine were added to therapy. Echocardiography excluded possible rhodococcus endocarditis. Since no response to antibiotherapy, bronchoalveolar lavage was obtained. EZN (+) bacili was detected on lavage. The agent was gram (+) and did not considered Mycobacterium tuberculosis. Claritromycine was added for possible atypical mycobacteria. Clinical improvement was seen and acute phase reactants decreased. Mycobacterium abscessus was detected by PCR at both hemoculture and bronchoalveolar lavage and confirmed at another accredited laboratory. It was sensitive to claritromycine and amicasine and semi sensitive to linesolide. Linesolide was discontinued at first month and continued with amicasine and claritromycine. Alveolar opacities were recovered and hypoxia was improved. Amicasine was discontinued at 2nd month. She was stabile on 6th month therapy of claritromycine.
A phase III trial evaluating three doses of citalopram for hot flashes: NCCTG trial N05C9
Authors: D. L. Barton, B. LaVasseur, J. A. Sloan, P. J. Stella, K. Flynn, M. Dyar, S. R. Dakhil, P. J. Atherton, B. Diekmann, C. L. Loprinzi
Journal: Journal of Clinical Oncology (2008)

9538 Background: Hot flashes are experienced by up to 75% of women and can negatively impact quality of life. Estrogen treatment has fallen out of favor, so new options are needed. Based on encouraging pilot data, this trial was designed to evaluate three doses of citalopram for effects on hot flashes. Methods: A randomized trial evaluated citalopram at doses of 10, 20 or 30 mg/day versus placebo for 6 weeks. Women recorded hot flashes for one week before starting treatment, then were titrated up to their assigned dose. The primary endpoint was change from baseline in hot flash score (frequency × severity) per a prospective daily hot flash diary. Secondary endpoints included hot flash frequency and activity interference. Toxicities were evaluated with a self-report questionnaire and NCI common terminology criteria. Eligibility included postmenopausal women with at least 14 bothersome hot flashes per week for the past month. A total of 50 patients per arm (N=200), provided 80% power for a two-sample t-test to detect a difference of 0.82 standard deviations or a drop of 29% from baseline in the hot flash score over placebo, with a 5% Type I error rate, including adjustment for multiple comparisons. Results: 254 patients were randomized onto this study. Data (below) for hot flash scores and frequency show improvement in hot flashes with citalopram with no significant differences among doses. Improvements were also seen for activity interference for all citalopram arms versus placebo (p<0.001). Patients on citalopram reported less distress related to hot flashes (p<0.001) and more satisfaction with hot flash control (p=0.02). Citalopram was well tolerated with no significant negative side effects. Conclusions: Citalopram is an effective, well tolerated agent in managing hot flashes. There does not appear to be a dose response above 10 mg/day. Arm Mean score reduction** P-values* Mean frequency reduction** P-values* Placebo 23% (CI: 11%-34% ) 20% (CI: 11%-30% ) 10 mg 49% (CI: 38%-60% ) p=0.0021 46% (CI: 36%-55% ) p=0.0004 20 mg 50% (CI: 39%-61% ) p=0.0011 43% (CI: 32%-53% ) p=0.0027 30 mg 55% (CI: 38%-73% ) p=0.0014 50% (CI: 38%-62% ) p=0.0002 * compared to placebo ** week 7-week 1 No significant financial relationships to disclose.
Clinical evaluation of intraperitoneal Pseudomonas exotoxin immunoconjugate OVB3-PE in patients with ovarian cancer.
Authors: By Lee H. Pai, Michael A. Bookman, Robert F. Ozols, Robert C. Young, John W. Smith, Dan L. Longo, Bruce Gould, Arthur Frankel, Edward F. McClay, Stephen Howell, Eddie Reed, Mark C. Willingham, David J. FitzGerald, Ira Pastan
Journal: Journal of Clinical Oncology (1991)

OVB3-PE is an immunotoxin composed of a murine monoclonal antibody reactive with human ovarian cancer and conjugated to Pseudomonas exotoxin (PE). Twenty-three patients with refractory ovarian cancer were treated intraperitoneally (IP) with escalating doses of OVB3-PE to study toxicity, pharmacokinetics, antiimmunotoxin antibody formation, and antitumor response. Dose-limiting CNS toxicity occurred after repeated doses at 5 and 10 micrograms/kg. Other non-dose-limiting toxicities included transient elevation of liver enzymes, fever, and gastrointestinal toxicity. Pharmacokinetics of IP and serum OVB3-PE were determined in 16 patients. Peak peritoneal fluid levels exceeded the in vitro median effective dose at all doses tested. At doses of 1 to 2 micrograms/kg, the immunotoxin concentration in the peritoneal fluid remained constant for up to 8 hours and dropped to negligible levels after 12 hours. At the 5 and 10 micrograms/kg doses, levels remained high for up to 24 hours (greater than 100 ng/mL) and then gradually decreased and became undetectable (less than 4 ng/mL) after 72 hours. Serum levels of OVB3-PE were also analyzed in 16 patients. At doses of 1 micrograms/kg and 2 micrograms/kg, serum levels were not detectable (less than 5 ng/mL). However, after doses of 5 or 10 micrograms/kg, peak serum level occurred at 24 hours after each dose and dropped to negligible levels by 72 hours. Sera from 12 patients were analyzed for anti-PE antibodies and antibodies to mouse immunoglobulin (HAMA). All patients developed antibodies against PE within 14 days of therapy. Domain II of PE appeared to be the most immunogenic portion of the PE molecule. HAMA was detected on day 14 of therapy in nine patients, on day 21 in two, and on day 28 in one patient. No clinical antitumor responses were observed. We conclude that IP OVB3-PE at dose levels of 5 micrograms/kg (x 3) and 10 micrograms/kg (x 2) is accompanied by dose-limiting toxic encephalopathy. Neurologic toxicity is likely to be due to crossreactivity of OVB3 to normal human brain tissue, which was not appreciated during preclinical screening.
Predictive value of preoperative plasma DNA level for early recurrence after resection in esophageal adenocarcinoma
Authors: F. Banki, S. Ayazi, J. A. Hagen, S. R. DeMeester, J. C. Lipham, J. M. Leers, K. D. Danenberg, P. V. Danenberg, T. R. DeMeester
Journal: Journal of Clinical Oncology (2008)

4545 Background: Esophageal cancer has a high recurrence rate and mortality due to presence of occult systemic disease at the time of diagnosis. At this time, there are no diagnostic tools to identify which patients are at risk. Plasma DNA is a molecular marker known to be elevated in patients with esophageal carcinoma. The aim of this study was to assess whether preoperative plasma DNA levels predict recurrence after resection for esophageal adenocarcinoma. Methods: Plasma DNA levels were measured using PCR prior to esophagectomy in 35 patients with esophageal adenocarcinoma. There was one perioperative mortality. Patients were followed every 3 months with CT Scan and yearly with PET Scan for a median of 20 months (IQR: 10–30). Results: An abnormal plasma DNA level was defined by the 95th percentile value in 44 asymptomatic volunteers (19 ng/ ml) as previously reported by us. The preoperative plasma DNA level was elevated in 28/35 (80%) of patients. All 7 patients with a normal preoperative plasma DNA level were free of recurrent disease at a median follow up of 19 months (IQR 12–34). In contrast, 12/27 patients (44%) with an elevated preoperative plasma DNA level developed recurrent disease at the median of 20 months (IQR 9–30). Freedom from recurrence was higher in patients with normal DNA level. (p = 0.045, Kaplan- Meier) This occurred even though, the number of patients with transmural invasion and the number with nodal involvement were similar in both groups. Twenty two patients had negative lymph nodes. In these patients, recurrence was more common in patients with elevated plasma DNA compared to those with normal DNA (7/18 vs. 0/4). Conclusions: An elevated preoperative plasma DNA level identifies patients at risk of recurrence for esophageal adenocarcinoma. This risk of recurrence applies even to patients with N0 disease. These patients should be considered for neoadjuvant or adjuvant therapy. Patients with a normal preoperative plasma DNA level may benefit from surgical resection alone. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Response Genetics Response Genetics Response Genetics
Tobacco smoke is a major source of indoor air pollution in Hungary's hospitality venues
Authors: Adam Domonkos Tarnoki, David Laszlo Tarnoki, Mark J. Travers, Andrew Hyland, Katherine Dobson, Laszlo Mechtler, Ildiko Horvath, K. Michael Cummings
Journal: European Respiratory Journal (2011)

Objective:  To compare the levels of indoor air pollution found in a sample of public locations in Hungary where smoking was and was not observed.   Methods:  The TSI SidePak AM510 Personal Aerosol Monitor was used to measure the concentration of particulate matter less than 2.5 microns in diameter (PM2.5) observed in the ambient air of 6 pubs, 5 restaurants, 11 cafes and 21 other locations in Budapest and Zalakaros between January and August 2008.   Results:  In the 27 places where smoking was observed the average PM2.5 level was 97.44 μg/m 3  [range: 3-487 μg/m 3 ]; compared to 5.5 μg/m 3  [range: 0-28 μg/m 3 ] in the 16 places where smoking was not observed.   Conclusions:  The levels of indoor fine particle air pollution measured in public locations in Hungary where smoking was observed were times higher than the levels in locations where smoking was not observed and in nearly all instances exceeded the levels that the World Health Organization and US Environmental Protection Agency have concluded are harmful to human health.
Comparison of criteria for assigning germ cell tumor patients to "good risk" and "poor risk" studies.
Authors: D Bajorin, A Katz, E Chan, N Geller, N Vogelzang, G J Bosl
Journal: Journal of Clinical Oncology (1988)

To evaluate the potential effect of patient selection on chemotherapy trials for patients with advanced germ cell tumors (GCT), four sets of eligibility criteria for poor risk trials were compared in 118 patients. A significant difference was found in the number of patients designated poor risk by the various criteria (P less than .005). Disagreement in the risk assignment by the various selection criteria was seen in 44% of patients. Initial complete response (CR) rates in patients designated poor risk by the various criteria ranged from 38% to 62%. Initial CR rates as high as 94% were seen in patients considered to be poor risk by one set of criteria, but good risk by another. Substantial differences in sensitivity, specificity, overall predictive value, and survival distributions were observed for the various selection criteria. Randomized trials will be necessary to reduce the influence of eligibility criteria on trial outcome and conclusions.
HBeAg 음성인 만성 B형 간염 환자에서 라미부딘 투여중 Viral Breakthrough의 발생 빈도
Authors: 장윤정, 임정윤, 조남영, 최창원, 백수정, 안수현, 최도원, 권용대, 김선숙, 권오상, 김주현, Jong Eun Yeon, Jin-Won Song, 변관수, 이창홍
Journal: Clinical and Molecular Hepatology (2002)

목적: 라미부딘 치료는 HbeAg 양성 만성 B형 간염환자에서 효과적인 것으로 알려져 있지만 HbeAg 음성 만성 B형 간염 환자에서 장기간의 치료효과에 BT의 발생률은 아직 확실치 않다. 이에 HbeAg 존재유무에 따른 BT의 발생률을 비교하고 BT의 발생과 YMDD 변이종의 출현과의 관계를 확인하고자 하였다. 대상과 방법: 최소한 9개월이상 라미부딘을 투여받은 만성 B형 관염 환자들 대상으로 하였으며 HbeAg 양성군은 205명, HbeAg 음성군은 49명이었다. 라미부딘 치료기간은 HbeAg 양성군 176개월, HbeAg 응성군은 155개월으로 양군간에 차이가 없었다. YMDD 변이종은 RELP 분석과 직접 염기서열 분석으로 확인하였다. 결과: 대상군의 임상적 특성은 HbeAg 음성군이 양성군에 비해 나이는 더 많았고 (43±9세 vs. 39±10세; p,0.05) 치료전 HBV DNA 역가가 낮았다. (670±1499 vs. 1877±5168 pg/ mL; p,0.01). 치료 12개월, 24개월의 누적 BT 발생률은 HbeAg 양성군에서는 12%, 39%였으며 음성군에서는 0%, 7%로서 음성군에서의 발생율이 양성군에 비하여 낮았다.(p<0.01). 다변량 분석으로 확인한 BT와 관계있는 유일한 인자는 HbeAg의 존재 유무였다.(p,0.05). YMDD 변이종은 HbeAg 유무에 관계없이 BT가 발생한 모든 예에서 확인할 수 있었으나 BT가 발생하지 않은 경우에서 YMDD 변이종의 발생률은 HbeAg 양성군보다 HbeAg 음성군에서 유의하게 더 높았다.(14.3% vs. 50.0%; P,0.01). 결론: HbeAg 음성 만성 B형 간염환자에서의 라미부딘 치료는 YMDD 변이종이 발생하여도 BT 발생 빈도가 낮아서 라미부딘의 지속적인 치료효과를 기대해 볼수 있으리라 생각된다.
Abstract 169: Angiotensin-II Induced Left Ventricular Remodeling Differs Between C57bl/6 Substrains
Authors: Sophie Cardin, Marie-Pier Scott-Boyer, Sylvie Picard, Tim L Reudelhuber, Christian F Deschepper
Journal: Circulation Research (2013)

Background: Although C57Bl/6 mice are widely used in cardiovascular research, little is known about possible substrain differences. We compared the left ventricular (LV) remodeling induced by angiotensin II (angII) in C57Bl/6J and C57Bl/6N mice, these 2 substrains corresponding to two main branches having diverged since 1951. Methods and Results: Male C57Bl/6J and C57Bl/6N mice were treated with angII (350ng/kg/min) or vehicle via mini-osmotic pumps for either 48h (for microarray profiling of gene expression and macrophage cytofluorometry counting) or 15 days (for both gene expression and histology). AngII (15d) induced fibrosis in LV from C57BL/6N (as shown by histology and col1a expression), but not in C57BL/6J. After 48h of treatment, about 100 genes responded in a strain-specific fashion, most responses being specific for C57Bl/6N mice. Among genes showing greater than 2-fold induction by angII (48h) in C57Bl/6N mice, there was enrichment for markers of macrophages activation and M2 polarization (including osteopontin, arginase1 and galectin3). These strain-specific differences were confirmed (both in LV tissues and macrophages isolated from LVs) by Q-RT-PCR, and occurred despite that fact that AngII increased the abundance of Cd11b+ macrophages to the same extent in both strains. Moreover, AngII (48h) increased expression of several markers of fibroblast activation (including Timp1, Lox and tenascin) in C57Bl/6N (both in LV tissue and fibroblasts isolated from LVs), but not in C57Bl/6J. Although one of the best known genetic differences in both substrains is the inactivation of the Nnt gene in C57Bl6/J mice, experiments performed in F2 mice do not indicate that the fibrotic response co-segregates with the Nnt mutation. Conclusions: Although angII-treatment induces macrophage recruitment in the LVs of both C57Bl/6J and C57Bl/6N mice, activation of cardiac macrophages and their M2 pro-reparative polarization (with subsequent activation of fibroblasts and synthesis of collagen) occurs only in the genetic C57Bl/6N background. The absence of macrophage activation and cardiac fibrosis in C57BL/6J may possibly explain some differences in experimental results obtained by various investigators using different C57BL/6 substrains.