tbuckley/cabot-search huggingface dataset:
A randomized, double-blind, placebo-controlled phase III trial comparing docetaxel, prednisone, and placebo with docetaxel, prednisone, and bevacizumab in men with metastatic castration-resistant prostate cancer (mCRPC): Survival results of CALGB 90401.
Authors: W. K. Kelly, S. Halabi, M. A. Carducci, D. J. George, J. F. Mahoney, W. M. Stadler, M. J. Morris, P. W. Kantoff, J. P. Monk, E. J. Small
Journal: Journal of Clinical Oncology (2010)

LBA4511 Background: The preclinical activity of vascular endothelial growth factor (VEGF) blockade, the inverse relationship of plasma and urine VEGF levels and survival in mCRPC patients (pts), and encouraging phase II data testing estramustine and docetaxel with bevacizumab suggested that VEGF blockade was an appropriate potential strategy in mCRPC. A phase III study testing the effect of adding bevacizumab to standard docetaxel and prednisone therapy administered every 3 weeks in pts with mCRPC was conducted. Methods: 1050 pts with chemotherapy naïve, mCRPC with evidence of progressive disease despite castrate testosterone levels and anti-androgen withdrawal, ECOG performance status ≤ 2, and adequate bone marrow, hepatic and renal function were eligible. Pts were prospectively randomized with equal probability to receive docetaxel (D:75 mg/m 2 IV over 1 hour q 21 days), plus prednisone (P) 5 mg po BID with either bevacizumab (B:15 mg/kg given intravenously q 3 weeks following D) or placebo. All patients received dexamethasone 8 mg PO 12, 3 and 1 hour prior to D. Randomization was stratified by predicted 24 mo survival probability, age and history of prior arterial thrombotic event. The primary endpoint was overall survival (OS). The trial was designed with 86% power to detect a 21% decrease in the hazard rate of death (equivalent to an increase in median OS from 19 months to 24 months) assuming a two-sided significance level of 0.05. The primary analysis was based on the stratified log-rank statistic adjusted for the stratification factors following observation of 748 deaths. Results: See Table . Conclusions: Despite an improvement in PFS, measurable disease response and post-therapy PSA decline, the addition of bevacizumab to docetaxel and prednisone did not improve OS in men with mCRPC, and was associated with greater morbidity and mortality. The median OS of pts treated with standard DP (21.5 m) was longer than previously reported (19 m). [Table: see text] [Table: see text]
Absence of second echelon involvement in melanoma patients with limited Breslow thickness and low sentinel node tumor load
Authors: T. Bogenrieder, M. Canninga van Dijk, W. Blokx, W. Stolz, P. J. van Diest
Journal: Journal of Clinical Oncology (2008)

9060 Background: The sentinel node (SN) procedure has become a widely used staging procedure for stage I/II melanoma. Most melanoma patients with a positive SN undergo completion lymph node dissection and, as a consequence, frequently experience associated morbidity. However, only approximately 20% of these patients have second echelon metastases. The aim of the present study therefore was to predict the absence of second echelon metastases in patients with a positive SN based on primary melanoma features, depth of SN invasion and SN tumor load. Methods: Of 70 SN positive patients, 18 had second echelon metastases. Penetrative depth of metastatic cells into the SN and SN tumor load (largest diameter and total tumour area) were assessed with morphometry. Primary tumour features concerned Breslow thickness, Clark level and ulceration. Results: None of the patients with a Breslow thickness <2.5 mm and a SN tumor load <0.3 mm2 had second echelon metastases. Similarly, none of the patients with a Breslow thickness <2.5 mm and SN depth of invasion <200 μm had second echelon metastases. Lastly, none of the patients with a Breslow thickness <2.5 mm and a diameter of the largest SN deposit <40 μm had second echelon metastases. Conclusions: A combination of limited Breslow thickness and low SN tumour load predicts absence of second echelon metastases in melanoma with a positive SN. We therefore propose that this subgroup may be spared completion lymph node dissection. No significant financial relationships to disclose.
Evaluation of missing quality of life assessments patterns in radiation therapy oncology group (RTOG) trials
Authors: K. Bae, D. Watkins-Bruner, Y. Yan, J. Coyne, B. Movsas
Journal: Journal of Clinical Oncology (2008)

20510 Background: Quality of life (QOL) is an important component of cancer research and allows fuller appraisal of the costs and benefits of treatments to patients. Evaluating similarities and differences in the patterns of missing QOL assessments can provide insight into predictors of missingness and optimal data collection schedules. Methods: Eighteen RTOG studies in symptom management (CCOP), brain, head and neck, gastrointestinal and lung disease sites with 5,846 eligible patients and five QOL instruments: Spitzer (981 pts), FACT (2665 pts), UW-QOL (882 pts), ADLS (122 pts), EORTC-QLQ (242 pts)] and MMSE (1957pts) were analyzed. The missing data patterns are categorized as follows: a patient complies at all time points (Complete), a patient does not comply at a time point and any subsequent time points but complies at all the previous time points (Monotone dropout), a patient does not comply at any time point (All missing), and all other patterns (Mixed). Results: There is no significant difference with respect to the pretreatment characteristics (age, gender, treatment, race, highest education) among the four missing patterns in each disease site and instrument. However, a higher rate (3–35%) of the Complete pattern can be found in CCOP trials for all QOL instruments than other disease sites (1–22%) and lower rate of All missing vs. other diseases (4- 7% vs. 2–27% respectively). The compliance rates of the missing reason in the All missing pattern are consistently lower than that of the Monotone pattern. ‘Institutional error’ and ‘due to illness’ are two major reasons for missing in most of the instruments. Also, baseline mean QOL scores of patients who comply all time points tend to be higher than that of patients who do not. Conclusions: There is no significant difference with respect to the pretreatment characteristics among the four missing patterns. CCOP trials, where the QOL assessments are mandatory show lower rates for the All missing pattern than other disease sites and higher rates of the Complete pattern across instruments. Higher compliance rates may be achievable by addressing “Institutional error,” which is the major reason for missing data. No significant financial relationships to disclose.
Ethnic minority participation in Community Clinical Oncology Program (CCOP) research studies
Authors: C. D. Figueroa-Moseley, G. R. Morrow, P. Jean-Pierre, J. Purnell
Journal: Journal of Clinical Oncology (2009)

1550 Background: Low minority participation in clinical research is concerning for both research and for the public health. Objective: The aim of this project was to investigate barriers and successes in minority participation in cancer medical research and cancer clinical trials. More specifically to: (1) determine major environmental, cultural, and economic barriers confronted by minority patients with cancer; and (2) determine the components of an environment that supports greater recruitment and retention of minorities to Clinical Community Oncology Practice (CCOP) cancer studies. Methods: Six focus groups consisting of 8 to 12 current or former minority cancer patients and 18 health care practitioners, from geographically diverse areas, were recruited to participate in this qualitative study. Focus group participants were asked questions about their attitudes and beliefs concerning their cancer and medical research. Health care practitioners were questioned on site recruitment and retention practices. Results: Two major thematic areas emerged for providers: barriers minority recommendation to trials and reasons for why minorities are underrepresented in trials. The three thematic areas for focus group participants were perceptions of medical research, reasons for participation or nonparticipation, and effects of Tuskegee Syphilis Study on participation. Conclusions: The Tuskegee Syphilis Study may have been a major impetus for why many Blacks and other minorities in this sample do not participate in medical research. Providers seem to state what was obviously important in connecting with the community, however, their actions in the community varied. This qualitative study gives voice to communities which mistrust the medical community in general and medical research in particular, and highlights the need for interventions bridging the community and research. No significant financial relationships to disclose.
Abstract 17015: Prognostic Value of Elevated Pulmonary Artery Pressure in Patients with Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement
Authors: Asim M Rafique, Hasan Jilaihawi, Niraj Doctor, Chakravarty Tarun, Mohammad Kashif, Doumanian Aik, Stegic Jasminka, Lauren Contreras, Gheorghiu Mitch, Nakamura Mamoo, Gregory Fontana, Wen Cheng, Raj R Makkar
Journal: Circulation (2012)

We retrospectively evaluated pulmonary artery pressure (PAP), clinical and echo-Doppler parameters to predict 1year mortality in 211 patients (pts) enrolled in PARTNER trial at single US center. Ag...
Prolongation of TTP by maintenance therapy with PLD in a multicenter phase III randomized trial following standard chemotherapy for MBC: GEICAM 2001–01 study
Authors: E. Alba, M. Ruiz-Borrego, M. Martín, M. Margelí, Á. Rodríguez-Lescure, P. Sánchez-Rovira, A. Ruiz, N. Ribelles, E. Calvo, A. Casado
Journal: Journal of Clinical Oncology (2007)

1007 Background: We had previously shown that sequential A→T is a reference treatment as first-line CT for MBC patients (pt) (JCO 2004, (22), 2587–2593). However, responses are short-lived and time to progression (TTP) is also short. Maintenance chemotherapy (MCT) with LPD could improve TTP without relevant additional toxicity. Methods: All pt received an induction CT with 6 cycles (cy) of A→T. Pt with a complete or partial response (CR, PR), or stable disease (SD) were randomly assigned to either LPD (40 mg/m 2 q4wk × 6 cy) or observation (O) from May 2002 to Dec 2006. Eligible pt had adequate bone marrow, renal, hepatic and cardiac functions (by left ventricular ejection fraction, LVEF). The study hypothesis assumed a median TTP since start of induction CT in O arm of 10.5 months (m), and a prolongation of TTP of 66% with MCT. Therefore, 154 pt (77 per arm) were necessary (one-sided a and 1-β errors of 0.01 and 0.8). Results: Pt accrual was completed in December 06. 122 and 136 pt (60/66 in LPD vs. 62/70 in O) are currently evaluable for efficacy and safety. Median age was 57 yr (30–74). Status disease in pt assigned to LPD vs. O: 2 (3%) vs. 6 (9%) of pt had CR, 31 (47%) vs. 43 (61%) had PR; 33 (50%) vs. 21 (30%) had SD. 291 cy of LPD were administered (median 6, range 0–6). Neither relevant LVEF decrease nor clinical congestive failure were seen. Nausea/vomiting and alopecia incidence was negligible. G3 hand-foot syndrome was present in 3 pt/3 cy (5/1%). Median TTP in LPD arm was 16.04 m (14.06–18.02), vs. 9.96 m (8.87–11.05) in O arm, p=0.0001. Conclusion: Maintenance therapy with LPD significantly prolongs TTP in MBC pt after a first-line CT without significant clinical toxicity. No significant financial relationships to disclose.
VEGF, EGF, HGF, and PDGF levels during chemotherapy in patients with metastatic colorectal cancer
Authors: O. Er, M. Inanc, M. Dikilitas, M. Ozkan, H. Karaca, R. Saraymen, F. Elmali
Journal: Journal of Clinical Oncology (2009)

4057 Background: Colon cancer is the third most common type of cancer in USA. Angiogenesis is necessary for the growth and metastasis of tumors in colorectal cancer (CRC). Increased angiogenesis in the primary tumor has been associated with poor prognosis and relapse of the disease. The aim of the present study was to measure plasma levels of the angiogenic factors in metastatic CRC patients before and after chemotherapy and to correlate with prognosis, in order to estimate the possible predictive value of angiogenic factor levels. Methods: Thirty-eight patients with metastatic CRC were recruited to the study and blood samples were taken to measure VEGF, EGF, HGF and PDGF before chemotherapy. All patients received XELOX (Capecitabine+Oxaliplatin) and response was assessed according to their clinical and radiologic evaluation after three cycles of XELOX. Angiogenic factors were measured after third cycle of chemotherapy. Statistical analysis was performed by SPSS 15.0 package program. Kolmogorov-Smirnov, Wilcoxon and 2 sample T test were used. Results: Eighteen patients (47.3%) achieved partial response (PR), 10 (26.3%) stable disease (SD), and 10 (26.3%) progressive disease (PD). VEGF, EGF, HGF and PDGF levels at baseline and after three cycles of chemotherapy are summarized in table . After 3 cycles of XELOX therapy VEGF, EGF, HGF and PDGF levels significantly decreased respectively, (p&lt;0.0001, p=0.011, p=0.049, p&lt;0.0001), in PR group. PDGF levels significantly decreased in SD group (p&lt;0.0001). However, other angiogenic factors were not influenced. Serum HGF levels significantly increased (p&lt;0.046) after 3 cycles of chemotherapy, however, VEGF, EGF, and PDGF levels were not significantly different in patients with PD. Conclusions: Significant decrease in VEGF, EGF, HGF and PDGF levels correlate with PR and indicate good prognosis in patients with advanced CRC. However, increased HGF level is associated with PD. [Table: see text] No significant financial relationships to disclose.
A Prognostic Model of Survival After First Hospital Discharge of Cancer Patients
Authors: M.A. Vicente Conesa, A. Fernanadez, M. Zafra, P.La Morena De Barrio, I. Ballester, E. Garcia-Garre, E. Urrgeo, A. Carmona-Bayonas, F. Ayala de La Peña
Journal: Annals of Oncology (2014)
Functional antibodies targeting AMIGO-2 demonstrate in vivo efficacy in human pancreatic carcinoma xenograft models
Authors: Isao Kohno, Keiko Katsumi, Yukiko Mori, Lilin Zhang, Aya Sakamoto, Hirokazu Satoh, Hiroyuki Aburatani
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3988 

AMIGO-2 (DEGA/Alivin1) is a type I transmembrane protein which is overexpressed in human pancreatic carcinomas. The extracellular domain of this molecule contains six leucine-rich repeats (LRRs) flanked by cystein-rich LRR NH2- and COOH-terminal domains and by a single Ig domain closed to the transmembrane region. This twin motif structure has been implicated in axon tract development of the nervous system. Using the GeneChipU133 Plus2.0 (Affymetrix), we found that AMIGO-2 mRNA was expressed approximately 6.3 fold higher in moderate or lower differentiated pancreatic carcinoma tissue compared to normal tissue. To examine AMIGO-2 as a potential therapeutic target for pancreatic carcinoma, we generated a series of mouse monoclonal antibodies against AMIGO-2 by immunizing mice with the extracellular domain of CHO cell expressed AMIGO-2. Immunohistochemical analysis was performed using a tissue micro array containing 62 paraffin embedded pancreatic carcinoma specimens, of which 42 specimens (68%) were found to be positive for AMIGO-2. Importantly, no staining was observed in normal specimens from the liver, kidney, heart, pancreas, colon, spleen, skin, brain or lung, whereas the antibodies only weakly reacted with epithelial cells in stomach, salivary gland and thyroid. In vitro assays revealed that several AMIGO-2 targeting antibodies induced complement dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) activity against an AMIGO-2 transfected human pancreatic MIA PaCa2 cell line in a dose dependent manner. In vivo experiments using an established AMIGO-2 transfected MIA PaCa2 subcutaneous tumor xenograft model in SCID mice, showed that one of the AMIGO-2 targeting antibodies, PPZ3124, inhibited tumor growth in a dose dependent manner. Once the tumor volume reached 100-150mm3, PPZ3124 was intravenously administered once every three days for 30 days at a dose of 10, 3, or 1 mg/kg (n=15). Tumor volume (mm3, mean±SE) was reduced by 90% (427±194), 70% (1617±418), and 50% (2443±488), respectively, at each dose relative to an isotype matched control antibody (4888±523). Body weights of PPZ3124-administered mice were similar to those of an isotype matched control antibody-administered mice throughout the experiments. Furthermore, we found that 1mg/kg of PPZ3124 had an equivalent effect to that of the chemotherapeutic Gemcitabine (Gemzar) (80mg/kg) administered intraperitoneally. These results demonstrate that the naked antibody against AMIGO-2 may have therapeutic value in treating human pancreatic cancer. To our knowledge, this is the first evidence that AMIGO-2 is a potential therapeutic target for pancreatic cancer therapy.
Abstract 19899: TEVAR in Acute Type B Aortic Dissection: Insights from the International Registry of Acute Aortic Dissection (IRAD), Interventional Cohort (IVC)
Authors: Guido H van Bogerijen, Himanshu J Patel, Gilbert R Upchurch, Daniel G Montgomery, Christoph A Nienaber, Eric M Isselbacher, Rossella Fattori, Nimesh D Desai, Joseph E Bavaria, Marco Di Eusanio, Thoralf M Sundt, Thomas G Gleason, David M Williams, Kim A Eagle, Santi Trimarchi
Journal: Circulation (2014)

OBJECTIVE:  Thoracic endovascular aortic repair (TEVAR) has evolved in to a common therapy for complicated acute type B aortic dissection (ABAD). Recently, the International Registry of Acute Aortic Dissection (IRAD) database was expanded with an interventional cohort (IVC) to further examine details of interventional and surgical treatments.   METHODS:  ABAD patients treated with TEVAR enrolled in IRAD IVC were studied (n=157). Mean age at intervention was 62±13y. Intra-procedural details were analysed and related to in-hospital outcomes. Indications for TEVAR were identified in 63%, including malperfusion (41%), periaortic hematoma (18%), hypotension/shock (2%), refractory/recurrent pain and hypertension (38%), and aortic diameter > 5.0 cm (4%).   RESULTS:  addition to TEVAR, visceral artery stenting (including celiac, SMA and renal artery) was required in 22%. This cohort was more likely to manifest malperfusion (50 vs 14%, p=.001) and acute renal failure (46 vs 8%, p   CONCLUSIONS:  The extent of disease and complexity of the procedure, indicated by several patient- and TEVAR specific details, dictates adverse early outcomes in ABAD after TEVAR. Knowledge of those interventional details may be of importance in the perioperative assessment of patients presenting with ABAD.
Elevated plasma concentrations of C-flanking gastrin-releasing peptide in small-cell lung cancer.
Authors: J J Holst, M Hansen, E Bork, T W Schwartz
Journal: Journal of Clinical Oncology (1989)

Many small-cell lung cancers (SCLCs) produce gastrin-releasing peptides (GRPs) (mammalian bombesin) but the plasma concentration of GRP is rarely elevated, possibly because of its rapid elimination. We developed a radioimmunoassay for the C-terminal flanking peptide of proGRP and measured its concentration in plasma from 71 patients with SCLC, in 27 healthy subjects and in 49 patients with other diseases including lung carcinomas. In addition, we studied the molecular size of immunoreactive C-flanking peptide in two SCLC cell lines and in plasma from SCLC patients. The concentration of immunoreactive C-flanking peptide in normal subjects and in control patients did not exceed 10 pmol/L and 26 pmol/L, whereas 72% of the SCLC patients had C-flanking peptide concentrations above 10 pmol/L. In patients with extensive disease (n = 35) the median concentration was 71 pmol/L (range, 10 to 940). ProGRP C-flanking peptide levels paralleled the clinical course in 12 patients. The molecule(s) responsible for the immunoreactivity had a molecular size of about 8 to 10 kd in both patient plasma and tumor cell lines, suggesting that the measured peptide(s) represented major fragment(s) if not the entire C-flanking peptide of proGRP. Thus this peptide(s) seems to be a useful marker for SCLC.
Final analysis of a phase I single dose-escalation study of the novel polo-like kinase 1 inhibitor BI 6727 in patients with advanced solid tumors.
Authors: T. Gil, P. Schöffski, A. Awada, H. Dumez, S. Bartholomeus, J. Selleslach, M. Taton, H. Fritsch, P. Glomb, G. M. Munzert
Journal: Journal of Clinical Oncology (2010)

3061 Background: BI 6727 is a highly potent and selective inhibitor of the serine-threonine Polo-like kinase 1 (Plk1), a key regulator of cell cycle progression. BI 6727 is a second generation dihydropteridinone derivative with distinct pharmacokinetic (PK) properties. Here, final safety and efficacy data are presented. Methods: Sequential cohorts of three to six patients with progressive advanced or metastatic solid tumors received a single 1 hour infusion of BI 6727 every three weeks, following a toxicity guided dose escalation design. A total of 65 patients were treated at doses from 12 to 450 mg including a cohort of 29 patients at the recommended phase II dose of 300 mg for a thorough characterization of safety. Results: Reversible hematotoxicity was the main side effect with thrombocytopenia, neutropenia and febrile neutropenia constituting the dose limiting toxicities. Anemia in 22% (grade 3: 8%), neutropenia in 15% (grade 3/4: 14%), thrombocytopenia in 14% (grade 3/4: 14%) and fatigue in 15% (all grade 1/2) of patients were the most frequent drug-related side effects. The MTD was 400 mg; however, 300 mg was the recommended dose for further development based on overall safety. There was no evidence of cumulative toxicity. PK were evaluated in 47 patients and demonstrated linearity in the therapeutic dose range, a large volume of distribution (>4,000 L), moderate clearance (706 mL/min) and a long half-life of around 110 hours. Renal and metabolic clearance was limited with <5% of dose and approximately 20% of parent exposure, respectively. Confirmed partial responses were observed in patients with advanced urothelial cancer, ovarian cancer, and melanoma. Stable disease as best response was reported in 48% of patients. Six patients remained progression-free for more than 6 months, two patients for 403 and 550 days. Conclusions: Final data from this first-in-man trial confirm the favorable PK and safety profile of the potentially first-in-class Plk1 inhibitor, BI 6727. Encouraging antitumor activity has been observed supporting Plk1 as a therapeutic target and further clinical development of this compound. Phase II monotherapy and combination trials are currently ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Boehringer Ingelheim Boehringer Ingelheim Boehringer Ingelheim Boehringer Ingelheim