tbuckley/cabot-search huggingface dataset:
The ENCHANT-1 trial (NCT01677455): An open label multicenter phase II proof of concept study evaluating first-line ganetespib monotherapy in women with metastatic HER2-positive or triple-negative breast cancer (TNBC).
Authors: Ahmad Awada, Angel Augusto Rodriguez, Anthony Kong, John Kalil Erban, Javier Cortes, Max S. Mano, Edith A. Perez, Iman El Hariry, Vojislav M. Vukovic, Florentina Teofilovici, Ilker Yalcin, Robert Bradley, David A. Cameron
Journal: Journal of Clinical Oncology (2013)

TPS1136 Background: Hsp90 is a molecular chaperone protein required for the stabilization and activation of many proteins, referred to as Hsp90 ‘clients’, including those commonly implicated in breast tumorigenesis such as HER2, EGFR, ER, PI3K, AKT, P53 and VEGFR. Ganetespib is a novel triazolone inhibitor of Hsp90 being studied in over 20 clinical trials, with over 700 patients treated to date. Ganetespib is ~50x more potent than 1 st -generation Hsp90 inhibitors, and has been well tolerated in clinical trials with a favorable safety profile. Mild to moderate, transient diarrhea is the most common adverse event associated with ganetespib infusion and is manageable with appropriate supportive care. Ganetespib has shown activity in preclinical models of HER2+, ER+/PR+ and triple negative breast cancer (TNBC). In a phase I trial, ganetespib demonstrated single-agent clinical activity in HER2+ disease with an objective response rate (ORR) of 15% and a disease stabilization rate of 46% in heavily pretreated patients. This efficacy-screening study is designed to provide further evidence of ganetespib activity and identify potentially predictive biomarkers in metastatic breast cancer. Methods: The ENCHANT-1 trial is an international, first-line Phase II study in two cohorts of breast cancer patients: Cohort A, HER2 amplified (n=35), and Cohort B, TNBC (n=35). HER2+ patients must have received prior anti-HER2 therapy in the adjuvant setting. Patients are treated with ganetespib at 150 mg/m 2 twice weekly on a three out of four-week regimen. Primary endpoint: ORR assessed using RECIST1.1 criteria. Key secondary endpoints include metabolic effects as assessed by PET/CT at week 3. Tumor genetic signature and proteomic profiling are performed on patient’s tumors in an effort to develop biomarkers of response. At the time of submission 6 patients have been enrolled into this study. Clinical trial information: NCT01677455.
Simvastatin plus capecitabine-cisplatin (XP) versus placebo plus capecitabine-cisplatin (XP) in patients with previously untreated advanced gastric cancer: A double-blind randomized phase 3 study.
Authors: Seung Kim, Won Ki Kang, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Jung Hun Kang, In Gyu Hwang, Sang-Cheol Lee, Keon-Woo Park, Hyo Rak Lee
Journal: Journal of Clinical Oncology (2014)

4066 Background: Patients with advanced gastric cancer (AGC) have a poor prognosis and few efficacious systemic treatment options. We aimed to the addition of synthetic 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitor, simvastin to capecitabine-cisplatin (XP) in patients with previously untreated advanced gastric cancer. Methods: In this double-blind, placebo-controlled, phase III study, we enrolled patients aged 18 years or older with histological or cytological confirmed metastatic (M1) adenocarcinoma of stomach or gastroesophageal junction at 9 centres in the KOREA. Patients, stratified by disease measurability and participating site, were randomly assigned (1:1) to receive capecitabine 1,000mg/m2 twice daily for 14 days and cisplatin 80 mg/m2 on day 1 every 3 weeks plus either simvastatin 40 mg or placebo, once daily. Cisplatin was given for 8 cycles; capecitabine and simvastatin were administered until disease progression or unacceptable toxicities. The primary end point was progression free survival (PFS). We assessed safety in all patients who received at least one dose of study drugs. This study is registered with ClinicalTrials.gov, number NCT01099085. Results: Between February 2009 and November 2012, 244 patients were enrolled and assigned to treatment groups (120 simvastatin, 124 placebo). Median PFS for 120 patients allocated XP plus simvastatin was 5.2 months (95% CI 4.3-6.1) compared with 4.63 months (95% CI 3.5 -5.7) for 124 patients who were to allocated to XP plus placebo (hazard ratio 0.930, 95% CI 0.684-1.264; p=0.642). 63 (52.5%) of 120 patients in simvastatin group and 70 (56.4%) of 124 had grade 3 or higher adverse events. Most common grade 3 or higher adverse events were neutropenia (40.5%, simvastatin plus XP; 51% placebo plus XP), anemia (13.3% v 10.5%) and anorexia (7.5% v 10.5%). Conclusions: Addition of 40 mg simvastatin to XP does not increase PFS in our trial, although it does not increase toxicity. Low dose of simvastatin (40mg) to chemotherapy is not recommended in untargeted population with advance gastric cancer. Clinical trial information: NCT01099085.
Timed sequential therapy of the selective T-type calcium channel blocker mibefradil and temozolomide in patients with recurrent high-grade gliomas
Authors: Matthias Holdhoff, Xiaobu Ye, Jeffrey G Supko, Louis B Nabors, Arati S Desai, Tobias Walbert, Glenn J Lesser, William L Read, Frank S Lieberman, Martin A Lodge, Jeffrey Leal, Joy D Fisher, Serena Desideri, Stuart A Grossman, Richard L Wahl, David Schiff
Journal: Neuro-Oncology (2017)

Mibefradil (MIB), previously approved for treatment of hypertension, is a selective T-type calcium channel blocker with preclinical activity in high-grade gliomas (HGGs). To exploit its presumed mechanism of impacting cell cycle activity (G1 arrest), we designed a phase I study to determine safety and the maximum tolerated dose (MTD) of MIB when given sequentially with temozolomide (TMZ) in recurrent (r)HGG.Adult patients with rHGG ≥3 months from TMZ for initial therapy received MIB in 4 daily doses (q.i.d.) for 7 days followed by standard TMZ at 150-200 mg/m2 for 5 days per 28-day cycle. MIB dose escalation followed a modified 3 + 3 design, with an extension cohort of 10 patients at MTD who underwent 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) PET imaging, to image proliferation before and after 7 days of MIB.Twenty-seven patients were enrolled (20 World Health Organization grade IV, 7 grade III; median age 50 y; median KPS 90). The MTD of MIB was 87.5 mg p.o. q.i.d. Dose-limiting toxicities were elevation of alanine aminotransferase/aspartate aminotransferase (grade 3) and sinus bradycardia. The steady-state maximum plasma concentration of MIB at the MTD was 1693 ± 287 ng/mL (mean ± SD). 18F-FLT PET imaging showed a significant decline in standardized uptake value (SUV) signal in 2 of 10 patients after 7 days of treatment with MIB.MIB followed by TMZ was well tolerated in rHGG patients at the MTD. The lack of toxicity and presence of some responses in this selected patient population suggest that this regimen warrants further investigation.
Early outpatient palliative care in patients with metastatic NSCLC: A qualitative study.
Authors: Jaclyn Yoong, Elyse R. Park, Joseph A. Greer, Vicki A. Jackson, Emily R. Gallagher, William F. Pirl, Anthony Back, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2012)

9101 Background: Early outpatient palliative care (PC) is an emerging practice and its key components have not been defined. We conducted a qualitative analysis of data from a randomized controlled trial which demonstrated improved quality of life, mood and survival in outpatients who received early PC integrated with standard oncologic care versus standard oncologic care alone. Our objectives were to 1) identify the content and key components of early PC clinic visits, 2) explore timing of key components, and 3) compare the content of PC and oncology visit notes at the critical time points of clinical deterioration and radiographic disease progression. Methods: We chose a random selection of 20 patients with newly diagnosed metastatic NSCLC who received early PC who survived within 4 time frames: less than 3 months (n=5), 3 to 6 months (n=5), 6 to 12 months (n=5) and 12 to 24 months (n=5). We performed content analysis on PC and oncology electronic health record notes of these patients using NVivo 9 software. Results: Addressing symptoms and coping ability were the most prevalent components of the PC clinic visits. The content of initial visits focused on building relationships and rapport with patients and their families and illness understanding. Discussions about prognostic awareness occurred during earlier visits while goals of care and hospice discussions occurred in later visits. The frequency of addressing these components was similar regardless of patients’ length of life. Comparing PC and oncology visits around critical time points, both included discussions about current illness status and goals of care; however PC visits emphasized symptoms, coping, and implications of anti-cancer treatments, while oncology visits focused on medical discussions about treatment plans. Conclusions: Early PC clinic visits emphasize managing symptoms, strengthening coping, and cultivating illness understanding and prognostic awareness in a structured, responsive and time-sensitive model. Around critical clinical time points PC and oncology visits have distinct features that suggest a key role for PC involvement while enabling oncologists to focus on anti-cancer management.
UTILIDAD DE LA ULTRASONOGRAFIA ENDOSCÓPICA (USE) Y LA PUNCIÓN (USE-PAAF) EN EL DIAGNÓSTICO DE LAS LESIONES QUÍSTICAS DEL PÁNCREAS (LQP)
Authors: L Argüello Viúdez, N Alonso Lázaro, D Alvarez De Sotomayor Bierman, C Satorres Paniagua, M Bustamante Balén, MJ Artes Martínez, M Prieto Rodríguez, M Ponce Romero, V Pons Beltrán
Journal: Endoscopy (2015)

Material y Metodo: Estudio prospectivo de una cohorte de pacientes remitidos para USE por LQP en radiología.
Prognosis and patterns of failure after curative pancreaticoduodenectomy for early-stage ampullary adenocarcinomas.
Authors: Adriana Regina G. Ribeiro, Milton Jose B Silva, Wilson Luiz Costa, Joyce Maria L. Maia, Fernando Vidigal Padua, Alessandro Landskron Diniz, Heber Salvador de Castro Ribeiro, Felipe José Fernandez Coimbra, Celso Lopes Mello, Maria D. Begnami, Aldo A. Dettino, Maria Nirvana Formiga, Augusto Akikubo Rodrigues Pereira, Marcello Ferretti Fanelli
Journal: Journal of Clinical Oncology (2012)

e14728 Background: Ampullary cancer (AC) is a rare malignancy. There is no consensus about the role of adjuvant radiotherapy and chemotherapy, mainly for early-stage tumors. Methods: Between 2007 and 2012 we performed a retrospective analysis of patients with AC that underwent a pancreaticoduodenectomy (PD) with curative intent in our institution. Results: Twenty-four patients underwent (PD), (M:F=13:11), median age was 63 (range35-83), 87% had R0 resection, median of resected lymph-nodes was 8.5 (range 2-30), 29% had positive lymph-nodes, 46% had perineural invasion, 21% had vascular invasion, 29% had lymphatic invasion, 50% had tumors &gt; 2 cm, 54% had moderately differentiated tumors. AJCC stage pathologic grouping was: I=37,5%, II=29%, III=33%; Median follow-up was 27 months, median progression free survival was 29 months and median overall survival was 101 months. Only lymph-node status was independent prognostic factor for disease free survival on multivariate analysis (p=0,045, HR: 7,8). Among patients with early-stage tumors (n=13), only one received adjuvant therapy. The relapse rate was 23% and 50%, for stage I and IIa tumors, respectively. Among the recurrences, 80% of relapses were distant metastasis without local relapse. In patients with stage IIb and III tumors (n=11), 63,6% received adjuvant treatment (57% chemotherapy and 43% radiochemotherapy). The relapse rate was 100% and 75%, respectively, and 66% of these relapses were distant metastasis without local relapse. 75% of patients who had local recurrence had tumors in stage IIb or III. Conclusions: Our study shows a high disease relapse rate in well-operated patients, even in early-stage tumors, with no nodal involvement, mainly with distant disease. The majority of patients who had local relapses had a more advanced stage and systemic relapses associated. This information can help guide decisions on the choice of adjuvant therapy.
BK Virus-Associated Hemorrhagic Cystitis Following Allogeneic Hematopoietic Stem Cell Transplantation; Incidence and Risk Factors
Authors: Feras Alfraih, Amjad Alhussaini, Farhan Anjum, Ghuzayel Mubarak Aldawsari, Fahad Alsharif, Said Y Mohamed, Walid Rasheed, Syed Osman Ahmed, Amr Hanbali, Marwan Shaheen, Riad O. El Fakih, Hazza A Alzahrani, Naeem A. Chaudhri, Fahad Almohareb, Mahmoud Aljurf
Journal: Blood (2016)
Radiographic tumor response in pediatric patients with newly diagnosed localized (LOC) or metastatic (MET) Ewing’s sarcoma (EWS) following neoadjuvant chemotherapy
Authors: M. K. Chuk, F. M. Balis, C. Mackall, D. Hawkins, N. Avila, B. C. Widemann, L. J. Helman, E. Fox
Journal: Journal of Clinical Oncology (2007)

20008 Background: Standard treatment for EWS includes vincristine, doxorubicin, cyclophosphamide (VDC) alternating with ifosfamide and etoposide (IE). Using this therapy, overall survival is 70% in patients with LOC EWS and 30% in patients with MET EWS. We compared the radiographic response to VDC and IE in patients with LOC or MET EWS. Methods: We conducted a randomized trial comparing pegfilgrastim to filgrastim in patients treated with VDC (cycles 1, 2, 5, 9, 11, 13) and IE (cycles 3, 4, 6–8, 10, 12, 14). Local control with radiation or surgery was initiated after cycle 5. We assessed radiographic response after VDC (C1,2) and IE (C3,4) using 1-dimensional (RECIST) and 2-dimensional (WHO) criteria. Measurements were performed using MEDx. Results: Twenty-one patients with EWS, median age 20y (6–25y), were enrolled; 16 were evaluable for this analysis. Primary tumors were in extremity (n=5) or central axis (n=11). Eight patients had MET disease (pulmonary only, n=4). Median (range) decrease in tumor size by WHO after C4 was 61% (40–92%) for LOC and 83% (47–94%) for MET. Decrease by treatment is presented in the table . Overall responses after 4 cycles for LOC patients were 5 PR, 3 SD using RECIST, and 6 PR, 2 SD using WHO. For MET patients, overall responses were the same using RECIST and WHO, 7 PR, and 1SD. Conclusion: Patients with MET EWS responded as well as those with LOC EWS after 4 cycles of neoadjuvant chemotherapy. Similar overall response was demonstrated using RECIST or WHO. Tumor response after VDC was greater than after IE, possibly due to sequence of administration, but patients had continued tumor response with IE. [Table: see text] No significant financial relationships to disclose.
Trastuzumab beyond progression in patients with HER2-positive advanced gastric adenocarcinoma: A multicenter AGEO study.
Authors: Juliette Palle, David Tougeron, Astrid Pozet, Emilie Soularue, Pascal Artru, Florence Le Roy, Olivier Dubreuil, Matthieu Sarabi, Nicolas Williet, Sylvain Manfredi, Jerome Martin-Babau, Christine Rebischung, Meher Ben Abdelghani, Ludovic Evesque, Johann Dreanic, Vincent Hautefeuille, Christophe Louvet, Thierry Lecomte, Julien Taïeb, Aziz Zaanan
Journal: Journal of Clinical Oncology (2017)

94 Background: Trastuzumab in combination with platinum-based chemotherapy is the standard first line regimen in HER2 positive advanced gastric cancer. However, there is no data concerning continuation of trastuzumab beyond first line progression. Methods: This retrospective multicenter study include all consecutive patients with HER2 + advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma who received after progression of trastuzumab plus platinum-based chemotherapy, a second line chemotherapy with irinotecan, taxane or platinum salt, with or without trastuzumab. The prognostic variables with P values ≤0.10 in univariate analysis were eligible for the Cox multivariable regression model. Results: From August 2007 to March 2015, 104 patients were included (median age, 60.8 years; male, 78.8%; PS 0-1, 71.2%) with advanced (metastatic : 99%) gastric (45.2%) or GEJ (54.8%) cancer. All patients had received first line treatment based on trastuzumab plus fluoropyrimidine and cisplatin (n=54; 51.9%) or oxaliplatin (n=50; 48.1%). As second line chemotherapy, 67 patients (64.4%) received FOLFIRI regimen, including 19 who have continued trastuzumab; 23 patients (22.1%) received a taxane regimen (paclitaxel or docetaxel), including 12 with trastuzumab; and 14 patients (13.5%) received a platinum-based chemotherapy (different from that used in first-line), including 8 with trastuzumab. When considering all regimens of second-line chemotherapy, continuation (n=39) versus discontinuation (n=65) of trastuzumab was significantly associated with an increase on PFS (4.4 vs 2.3 months; p=0.002) and OS (12.6 vs 6.1 months; p=0.001). In multivariate Cox model (including ECOG PS, tumor grade, number of metastatic site, and second-line treatment), continuation of trastuzumab was significantly associated with longer PFS (HR=0.56; 95%CI [0.35-0.89]; p=0.01) and OS (HR=0.47; 95%CI [0.28-0.79]; p=0.004). Conclusions: This study suggests that maintenance of trastuzumab plus second line chemotherapy beyond disease progression has clinical benefit in patients with HER2 positive advanced gastric cancer. These results deserve a prospective randomized validation.
Efficacy and cost of peripheral blood stem cell (PBSC) mobilization with low-dose cyclophosphamide (LD-CY) compared with plerixafor (P) in multiple myeloma (MM) patients (pts) treated with novel induction therapies.
Authors: Lubna Chaudhary, Farrukh Tauseef Awan, Aaron Cumpston, William W. Tse, Michael Craig, Mehdi Hamadani
Journal: Journal of Clinical Oncology (2013)

7040 Background: Efficacy and cost effectiveness of P vs. LD-CY mobilization in MM pts treated with novel induction therapies is not known. Methods: We analyzed the mobilization outcomes of 107 consecutive pts who underwent a planned, single autograft within 1-year of starting induction therapy with novel agents (thalidomide, lenalidomide, bortezomib) between 2003-2012. Pts undergoing mobilization with LD-CY/G-CSF (1.5gm/m 2 ) (n=74) were compared against those receiving P/G-CSF (0.24mg/kg) (n=33). Efficacy of PBSC mobilization was assessed by evaluating peak peripheral blood (PB) CD34+ cell counts, CD34+ cell yield on day1 of collection, total CD34+ cell collection, and total number of apheresis sessions. Mobilization failure was defined as failure to collect ≥2 x10 6 cells/kg body weight. Mobilization costs were calculated per patient in both groups. Centers for Medicare and Medicaid Services reimbursement rates and Red Book Average Wholesale Price were used for cost determination. Results: At baseline, the LD-CY and P cohorts were well balanced. Compared to LD-CY, P use was associated with higher median peak PB CD34+ cell count (68/µl vs. 36/µl, p=0.048), CD34+ yield on day 1 of collection (6.9 x10 6 /kg vs. 2.4 x10 6 /kg, p=0.001), and total CD34+ cell yield (11.6 x10 6 /kg vs. 7x10 6 /kg, p=0.001). Median numbers of apheresis sessions were 2 in each group (p=0.17). In pts with prior lenalidomide use, mobilization failure rate in the LD-CY group was higher compared to the P group (20% vs. 0%, p=0.01). P group had a higher number of pts collecting ≥10x10 6 /kg CD34+ cells (60.6% vs. 31%, p=0.01). Rate of infectious complications, transfusion requirements and hospitalizations was similar in both groups. The average total cost of mobilization in the P group was significantly higher compared to the LD-CY group ($28,980 vs. $19,627, p-value&lt;0.0001). Conclusions: Our data indicates that although associated with a significantly higher total mobilization cost, plerixafor produced a more robust PBSC mobilization, without any collection failures.
Skin rash and good performance status (PS) predict improved survival with gefitinib for patients with advanced non-small cell lung cancer (NSCLC)
Authors: M. K. Mohamed, S. Ramalingam, Y. Lin, W. E. Gooding, W. Cronin, J. R. Eckardt, C. P. Belani
Journal: Journal of Clinical Oncology (2004)

7097 Background: Gefitinib (Iressa®) is active as a single agent for the treatment of advanced NSCLC patients who have failed prior chemotherapy. For optimal utilization of gefitinib, effective methods to identify sub-sets of patients likely to benefit from treatment are necessary. We analyzed patients treated with gefitinib on an Expanded Access Program at our institutions to detect possible predictive factors for patient selection to future studies. Methods: Patients (N=178) with advanced NSCLC were treated with gefitinib (250 mg PO QD) upon progression from chemotherapy. Patients with ECOG PS of ≤ 2, adequate bone marrow, hepatic and renal function were eligible. Results: Baseline patient characteristics were: Median age: 68 years (range 29–100); males - 56%; Adenocarcinoma –49%, squamous –21%, bronchioloalveolar-6%, other –24%. Objective partial responses were noted in 4 (2.4%) and disease stabilization in 28 (17%) patients. The median survival (MS) was 6.1 months (95% CI 4.42–7.21) and median time to progression was 3 months (95% CI 2.0–3.0). The predictive factors analyzed were gender, skin rash, diarrhea and PS. Patients who developed a skin rash (any grade) had a MS of 11 months compared to 4.5 months for patients without a rash (P < 0.0001, log rank test). Patients with PS 0/1 and 2 had a MS of 5.8 months and 2.9 months respectively (P < 0.0001). Other factors did not impact survival. Conclusions: Occurence of skin rash and baseline PS of 0/1were associated with significantly improved survival for advanced NSCLC patients who failed prior chemotherapy, upon treatment with gefitinib. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca
Prognostic factors for overall survival in patients with metastatic castration-resistant prostate cancer: Secondary analysis.
Authors: Andrea Carolina Anampa-Guzman, Oliver Sulca-Huamani, Rushmely Perez-Mendez, Gloria Mendoza-Soto, Pamela Contreras Chavez, Rolig Aliaga
Journal: Journal of Clinical Oncology (2017)

e597 Background: The standard treatment for metastatic castration-resistant prostate cancer (MCRPC) is Docetaxel (DTX); however, it has serious adverse effects. It is necessary to know the prognostic factors for overall survival (OS) of patients with MCRPC treated with DTX. The aim of this study was to determine the prognostic factors for OS in patients with MCRPC treated with DTX. Methods: This study is a secondary analysis of the control arms of the clinical trials NTC00273338, NCT00519285 and NCT00988208. 1600 patients aged 18 years or older with MCPRC that received DTX and prednisone were included. Survival curves were estimated by Kaplan-Meier and comparison was done by log-rank test. Multivariate analysis for overall survival (OS) was performed with the Cox proportional hazard regression model. Results: The median OS time was 14.64 months. The 1-yr-OS and 2-yrs-OS were 86.2% and 28.6%, respectively. Patients with an ECOG score greater than 0 lived significantly less than the rest of patients (p = 0.00). The patients with an alkaline phosphate level (ALP) &gt; 200 had significantly lower OS (p = 0.00). In the multivariate analysis, the factors that influenced OS were ECOG, ALP, HB, LDH and number of metastases. Conclusions: Poor performance status, high alkaline phosphatase level, low hemoglobin level, high LDH and more than 2 metastases were the main prognostic factors in patients with metastatic castration resistant prostate cancer. [Table: see text]