tbuckley/cabot-search huggingface dataset:
ELYPSE 2: A prospective randomized trial comparing filgrastim (G-CSF) in primary and secondary prophylaxis in patients (pts) at high risk for febrile neutropenia (FN)
Authors: P. Biron, I. Ray-Coquard, A. Le Cesne, S. Dussart, C. Goilliot, T. Bachelot, A. Thyss, E. Gilles, S. Chabaud, J. Blay
Journal: Journal of Clinical Oncology (2006)

8614 Background: FN is a frequent life-threatening consequence of cytotoxic chemotherapy (CT). G-CSF reduces the risk of FN, but primary (1 ry ) prophylaxis using G-CSF may be cost efficient only if FN incidence is ≥20%. The identification of pts at high risk for FN with simple criterias would be useful in clinical practice. Here we report a randomized phase II trial comparing G-CSF in 1 ry vs 2 ry prophylaxis in a high risk group of pts (based on our risk model JCO 1996;14:737, Br J Cancer 2003;88:181). Methods: Pts ≥18 years with solid tumors or NHL at high risk for FN after CT were incluable: these were pts with day 1 or day 5 lymphocytes (Ly) count ≤700/μL AND “high risk CT” (HRCT) In pts with d1 and d5 Ly ≤700/μL, the observed incidence of FN was 40% and 66% respectively G-CSF (300 to 480μg/d from d6–12) was randomized either as in 1 ry prophylaxis (Arm 1), or as 2 ry prophylaxis after FN (Arm 2). Primary endpoint was the rate of grade 4 FN. Hypothesis was a reduction of 40% of the risk of FN with 1 ry prophylaxis. Results: Between 03/97 and 12/04, 137 pts were included in 7 centers. The median age was 53 years (range 18–80) with 54% males. Most frequent tumors were sarcomas (36%), breast carcinomas (18%), lymphomas (15%), head and neck carcinomas (10%), and lung carcinomas (6%). 23% patients had PS&gt;1 at the first line of chemotherapy. No difference was observed in terms of duration of hospitalization or antibiotherapy. Median number of days of G-CSF administration was 14 days (0–24) vs 0 (0–17) days (p&lt;0.0000). After the 1st course, grade 4 FN was 38% in Arm 2 (2 ry prophylaxis) and 25% in Arm 1 (1 ry prophylaxis), showing a 34% reduction of FN in arm 1 (p=0.14): 1 ry prophylaxis was associated with a significant reduction of FN using logistic regression (p=0.04). Incidence of FN after the 2 course in pts receiving 2 ry prophylaxis was 22%. Among the subgroup of pts with PS&gt;2 and Ly ≤700/μL, (a group with a reported 20% risk for early death, Br J Cancer 2001;85:816), 2 of 8 patients (25%) died after the 1st course, vs 0/13 in the G-CSF group (p=0.05). This difference was not significant in the whole group. Conclusions: This study confirms that lymphopenic pts receiving HRCT are a high risk group of pts for FN for whom 1 ry prophylaxis with G-CSF reduces the incidence of FN. [Table: see text]
Cancer genomes and their implications for understanding and managing cancer
Authors: Bert Vogelstein
Journal: Journal of Clinical Oncology (2009)

s1a Research over the past 25 years has shown that cancer is, in essence, a genetic disease. In the past three years, it has become possible to determine the sequence of nearly all the 21,000 protein-encoding genes in the human genome. The results of such sequencing in 68 tumors of the breast, colon, pancreas, or brain have led to new insights about the nature and diversity of the genetic alterations responsible for initiation and progression of tumors. The pathogenesis of solid tumors can best be understood as the cumulative result of alterations in approximately a dozen pathways that each regulate the balance between cell birth and cell death. The challenge for basic science is to understand these pathways in more detail. The challenge for clinical science is to devise approaches to use this new and extensive genetic information to improve diagnosis and therapy. Examples of how these challenges might be achieved in the future will be presented.
A retrospective single institutional analysis of bevacizumab and chemotherapy versus non-bevacizumab treatments for recurrent glioblastoma
Authors: P. Nghiemphu, C. Graham, W. Liu, T. Than, A. Lai, R. Green, R. M. Elashoff, T. F. Cloughesy
Journal: Journal of Clinical Oncology (2008)

2023 Background: Bevacizumab, a monoclonal antibody to vascular endothelial growth factor, has been shown to be effective in the treatment of recurrent glioblastoma in combination with chemotherapy compared to historical controls but not in randomized trials. Methods: We conducted a retrospective analysis of all patients treated at our institution for a recurrent glioblastoma to compare patients who received bevacizumab versus a control group of patients. We compared progression free survival (PFS) and overall survival (OS) between the two groups, and also compared these factors based on the age and performance status within each group. We also analyzed the impact of bevacizumab on quality of life by comparing change in performance status. Results: We identified 44 patients who received bevacizumab, and 79 patients who have not been treated with bevacizumab. There is a statistically significant improvement in PFS in the bevacizumab treated group, but only a trend toward better survival. Patients of older age (≥50) and poor performance status (KPS≤80) have significantly better PFS when treated with bevacizumab, and bevacizumab-treated older patients have significantly increase OS. Patients treated with bevacizumab also maintained their functional status longer than the control group. Conclusions: Bevacizumab in combination with chemotherapy can be a more effective treatment for recurrent glioblastoma and warrants further randomized prospective studies to determine its effect on survival. Bevacizumab also has more effect in those with older age and might reflect biological differences in glioblastoma in different age groups, and biological correlates should also be considered. Bev Control p value No 44 79 Age 54 55 0.86 KPS 82 82 0.8 Recurrence (%) 1st 50 100 2nd 32 0 3rd 18 0 PFS (mos) all (n) 4.25 (44) 1.82 (79) 0.01 age <50 (n) 4.01 (15) 2.01 (28) 0.85 age ≥50 (n) 4.60 (29) 1.87 (51) 0.0002 KPS >80 (n) 3.83 (24) 1.84 (36) 0.16 KPS ≤80 (n) 4.60 (20) 1.87 (43) 0.04 OS (mos) all 9.01 6.11 0.08 age <50 10.83 6.88 0.74 age ≥50 8.31 6.11 0.02 KPS >80 9.22 8.05 0.61 KPS ≤80 9.01 4.74 0.08 Time to KPS change (days) 252 120 0.006 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology Genentech™ BioOncology
Phase I Trial of Intraperitoneal Injection of the E1B-55-kd-Gene-Deleted Adenovirus ONYX-015 (dl1520) Given on Days 1 Through 5 Every 3 Weeks in Patients With Recurrent/Refractory Epithelial Ovarian Cancer
Authors: P. A. Vasey
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Resistance to chemotherapy in ovarian cancer is frequently associated with mutations in the p53 gene. The adenovirus dl1520 (ONYX-015) with the E1B 55-kd gene deleted, allowing selective replication in and lysis of p53-deficient tumor cells, has shown preclinical efficacy against p53-deficient nude mouse-human ovarian carcinomatosis xenografts. PATIENTS AND METHODS: We undertook a phase I trial of intraperitoneal dl1520 in patients with recurrent ovarian cancer. Sixteen women with recurrent/refractory ovarian cancer received 35 cycles (median, two cycles) of dl1520 delivered on days 1 through 5 in four dose cohorts: 1 × 109 plaque forming units (pfu), 1 × 1010 pfu, 3 × 1010 pfu, and 1 × 1011 pfu. RESULTS: The most common significant toxicities related to virus administration were flu-like symptoms, emesis, and abdominal pain. One patient receiving 1 × 1010 pfu developed common toxicity criteria grade 3 abdominal pain and diarrhea, which was dose-limiting. The maximum-tolerated dose was not reache...
Radiologic and pathologic prognostic factors after neoadyuvant chemotherapy for T3 rectal cancer (RC): 3-year update GEMCAD 0801-trial.
Authors: Isidro Machado, Gina Brown, Rafael Estevan, Antonieta Salud, Mabel Gil, Clara Montagut, Marcos Busto, Maria Jose Safont, Joan Maurel, Juan Ramón Ayuso, Jorge Aparicio, Jaime Feliu, Ruth Vera, Vicente Alonso, Javier Gallego, Martha Martin, Carles Pericay, Eva Ballesteros, Jesus Santos, Carlos Fernandez-Martos
Journal: Journal of Clinical Oncology (2015)

643 Background: Prognostic factors in RC treated only with neoadjuvant chemotherapy, have not been explored. We analized the prognostic value of clinical-radiological and pathological factors for disease-free, (DFS) and cumulative incidence of distant metastases (DM), for patients treated with preoperative capecitabine, oxaliplatin and bevacizumab (CAPOX-B) within our multicentre phase II GEMCAD 0801 trial. Methods: 46 patients were enrolled to evaluate safety and efficacy of neoadjuvant CAPOX-B followed by surgery. Results have been recently published (Oncologist 2014;19:1-2). Eligibility included baseline magnetic resonance (MR) showing a T3 tumour with mesorectal fascia potentially clear. Clinical, pathologic (ypN+, T or N downstaging, tumor regression grade [TRG], pathologic complete response [pCR]) and radiologic factors both at baseline (mr extramural venous invasion [EMVI]) and post neoadjuvant chemotherapy (ymr TRG, ymr lengh change [RECIST]), were analyzed. Univariate and multivariate analysis was performed. Results: With a median follow up of 36 months, fourteen patients experienced relapse (2 local, 11 distant, 1both). 3-year DFS was 69%. It was 95%/49% for T downstaging/no T downstaging (p=0.0009) and 95%/43% for mrEMVI positive/negative (p=0.0001), respectively. ymrTRG (Mandard) ranging from no regression, TRG 5, to complete response, TRG 1, p=0.0108 and ypN0/ypN+ (p=.02) were also significantly related to DFS in univariate analysis. The same factors and N-downstaging were also significant for cumulative incidence of DM. On Cox multivariate analysis, T downstaging and mrEMVI were the only independent prognostic factors for DM ( p=0.0363 and 0.0111 respectively) and DFS (p=0.0315 and 0.0277 respectively). Conclusions: T3 rectal cancer with MR detected EMVI positive and those without downstaging after neoadjuvant chemotherapy are associated with unfavourable prognosis. This suggests that future strategies for treatment intensification and surveillance could be based on EMVI and T staging. Clinical trial information: NCT00909987.
Bi-weekly fixed dose of gemcitabine (GEM) plus 24 hours infusion of cisplatin (CDDP) in advanced/metastastic pancreatic cancer (APC) patients: A phase II study
Authors: V. D. Ferrari, S. Grisanti, F. Valcamonico, V. Amoroso, S. De Ponti, G. Rangoni, P. Marpicati, L. Vassalli, E. Simoncini, G. Marini
Journal: Journal of Clinical Oncology (2008)

15639 Background: As single agent GEM is a standard therapy for APC. CDDP is the oldest platinum compound which appears to be active in the treatment of this cancer. GEM has demonstrated activity in combination with various CDDP regimens. A pooled retrospective analysis revealed that GEM plus CDDP compared with GEM increased OS and PFS. We evaluated safety, feasibility and efficacy of GEM plus CDDP (24 hours infusion) every 2 weeks in APC pts. Methods: From 2/2005 to 12/2006 37 pts entered in the study (male/female = 25/12), median age was 61 yrs (range 40–77), median ECOG performance status was 0/13 pts - 1/19 pts - 2/5 pts), predominant metastatic site was liver in 19 pts, lung in 7pts, 31 pts had metastatic diasease (8 pts were in relapse). Pain was reported at diagnosis in 21 pts. Comorbidity were diabetes in 10 pts, prior solid tumour in 4 pts, prior myocardial infarction in 2 pts. Median number of cycles was 8 (range 1 - 10), total number of cycles was 267. Schedule of treatment: GEM 1,250 (10 mg/m2/min infusion) day 1, CDDP 40 mg/m2 24 hours infusion day 1, hydratation with saline solution was administered to prevent renal failure. Cycles were repeated every 2 weeks. To prevent nausea and vomiting, 5-hydroxytryptamine-3 antagonists (5HT3) IV plus dexamethasone 12 mg IV were administered before chemotherapy and oral 5HT3 were given orally at standard doses for 2 days after chemotherapy. Results: We observed no CR, 6 PR (16%) and 20 SD (54%), 17 (46%) pts were alive 12 months after the beginning of chemotherapy and 17% after 18 months. Median OS was 12.5 months (range 2–42). Hematologic toxicity G3–4 was neutropenia in 8.1% of pts, anemia in 8.1% of pts, thrombocytopenia in 2.7% of pts. Nonhematologic toxicity was nausea/vomiting G2 in 5.4% of pts, mucositis/diharrea in 2.7% of pts, renal toxicity G2 in 2.7% of pts. No toxic death was reported. Conclusions: The addition of CDDP (c. i.) to GEM in pts with APC is feasible and safe; median survival was similar to what observed with other combinations of two or more cytotoxic drugs; the treatment is not expensive (150 euro/cycle). No significant financial relationships to disclose.
Response to azacitidine (AZA) in patients with secondary myelodysplastic syndrome
Authors: H. Abdulhaq, B. Haq, J. Rossetti, J. Lister, R. Shadduck
Journal: Journal of Clinical Oncology (2006)

6578 Background: Myelodysplastic syndrome (MDS) is characterized by maturation defects in hematopoietic progenitor cells that result in ineffective hematopoiesis, various cytopenias and risk of progression to acute myeloid leukemia. MDS can arise de novo or secondary to exposure to myelotoxic drugs or ionizing radiation. Secondary MDS (t-MDS) tends to have more aggressive behavior than de novo MDS. Azacitidine (AZA), a DNA methyl transferase inhibitor has activity in MDS. To date there is little data in patients with t-MDS Methods: The records of 21 patients with t-MDS treated with AZA between 05/96 and 01/06 were reviewed to determine response, duration of response and tolerability in these high-risk patients. 15 of the 21 patients received AZA as part of a National Cancer Institute special exception program (75mg/m 2 subcutaneously for seven days every four weeks). Patients who received at least 2 cycles were considered evaluable for response (N=16). All patients were evaluated for toxicity. The International working group standardized response criteria for MDS were used for evaluation. Results: Patients had a median age of 68 years; male: female ratio was 3:1. 11 patients had refractory anemia, 6 had refractory anemia with excess blasts, 3 had chronic myelomonocytic leukemia, 1 had refractory anemia with ringed sideroblasts. Response was seen in 8 (50%) of 16 patients, with 2 (12.5%) partial remissions, 6 (37.5%) showed major hematological response. The median duration of response was 12.3 months (range 4–38). Stable disease was seen in 5 patients (31%), with an average duration of 6.5 months (range 2–15). 3 patients failed therapy due to disease progression or death. Treatment was well tolerated in general, with the most side effects being nausea, vomiting, diarrhea and cytopenias. Febrile neutropenia was seen in 5 patients. Conclusions: Azacitidine appears to be effective and well tolerated in patients with t-MDS. [Table: see text]
Navigator program for breast cancer trial recruitment and enrollment at a county hospital
Authors: S. Donnell, A. M. Leitch, D. Rice, E. Gray, D. McKindles, R. Aravind, M. Warungi, F. Youssefi, C. Osborne, D. Tripathy
Journal: Journal of Clinical Oncology (2005)

598 Background: Only a small fraction of patients with breast cancer are enrolled on clinical trials, fewer from minority and underserved populations. Limited resources in county hospitals accentuate barriers to accrual. Methods: We designed a Patient Navigator program at the Breast Clinic at Parkland Hospital in Dallas, which serves a primarily Hispanic and African American population. Patients were identified at first diagnosis of breast cancer or at the time of recurrence. Demographic and clinical details were entered into a database and appropriate queries and secondary screening were performed to identify candidates to several open trials. At subsequent clinic visits, patients were systematically approached by study coordinators and faculty physicians. The number of eligible candidates, number of patients enrolled and reasons for not enrolling were recorded. Results: The Navigator program was fully implemented in October 2003 and data through October 2004 are presented. A total of 373 patients were screened. Racial/ethnic distribution was African American 45.6%, Hispanic 27.6%, White 20.1% and Asian 4.3%; 38.1% of patients were under age 50 and 5.4% were over 70. Of 373 patients, 308 episodes of eligibility were found (more than one for some patients) and 35 enrollments occurred. Neo-adjuvant trials are a special focus of the research program, and 79 patients were eligible, with 10 patients (12.7%) enrolled. Reasons for not enrolling included patient declining due to study procedures (20%), non-English speaking (21%), patient choice of mastectomy (18%), physician choice of alternate protocol (13%), co-morbidities (10%) and risk of non-compliance (10%). Only 1 eligible patient was not approached. For a node-negative cooperative group trial, 34 candidates were identified and 3 were enrolled (9%), with similar patterns of reasons for not enrolling. Data on additional trials and results by demographic variables will be presented. Conclusions: Implementing a Navigator program results in early identification of clinical trial candidates and can potentially increase enrollment onto clinical studies in a county hospital setting serving minority and underserved populations. Additional educational tools are needed. No significant financial relationships to disclose.
The clinical impact and outcomes of immunohistochemistry-only metastases in breast cancer
Authors: M. S. Pugliese, M. M. Stempel, S. M. Patil, M. Hsu, H. S. Cody, M. Morrow, M. L. Gemignani
Journal: Journal of Clinical Oncology (2009)

613 Background: Modern surgical and pathologic techniques can detect small volume axillary metastases in breast cancer. The clinical significance of these metastases was evaluated in comparison to patients with negative sentinel lymph nodes (Neg-SN). Methods: Retrospective database review from 1997 through 2003 for eligible patients with unilateral breast cancer and no history of significant non-breast malignancy identified 232 patients with sentinel lymph node (SLN) metastases identified only by immunohistochemical stains (IHC-SN). They were compared to 252 Neg-SN controls selected at random from the same database population. Statistical analysis was performed with 2-sample tests, Kaplan-Meier, and Cox regression methods. Results: IHC-SN patients had worse prognostic features and received more systemic therapy than controls (Table). Age and ER status were similar. In 123 IHC-SN patients treated with axillary dissection (ALND), 16% had macrometastases in the non-SLNs. Only one axillary recurrence occurred in the group of IHC-SN patients without ANLD (n=109). With median follow up of 5 years (range 0.01–12.0), 28 recurrences and 25 deaths occurred. There were no differences between cases and controls for recurrence-free survival (RFS) or overall survival (OS) both by univariate and multivariate models that included variables such as age, tumor size, chemotherapy and hormone therapy [HR 0.99 (95%CI 0.43–2.28, p=0.99) for RFS, HR 2.06 (95%CI 0.79–5.35) p=0.14 for OS]. In IHC-SN patients treated with ALND, patients with positive non-SLNs (n=20) tended to have worse RFS than those with negative non-SLNs (n=103) [RFS 89% vs. 97% at 5 yrs (p=0.06)]. Conclusions: A significant number of IHC-SN patients had a macrometastasis identified at ALND. In patients not undergoing dissection, axillary recurrence was a rare event. However, failure to identify additional metastases by omitting ALND may result in understaging and inadequate systemic treatment in some patients. [Table: see text] No significant financial relationships to disclose.
Doctors can withdraw feeding from patient in minimally conscious state, judge rules
Authors: C. Dyer
Journal: BMJ (2015)

Silverleaf phacelia (<i>Phacelia hastata</i> Douglas ex Lehm. var. <i>hastata</i> [Hydrophyllaceae]) is a versatile and hardy native plant species with an aesthetically pleasing flower, silver-tinged leaves, and the ability to respond positively to nursery propagation protocols. Attempts to germinate this species without suitable pretreatment, however, have resulted in low and erratic germination due to seed dormancy, even though previous anecdotal studies have identified seed treatments for freshly harvested seeds. After-ripened seeds were subjected to seed structure identification and the following experiments to classify dormancy and to determine effective and efficient seed treatments for growers: 1) examination of water uptake; 2) growth of excised embryos; 3) effect of gibberellic acid; and 4) effect of mechanical scarification. Based on the results of all observations and experiments, dormancy was classified as physiological. Germination was most successful with excised embryos (100%), scarification (87%), and GA soak (48%), with scarification being the most effective and labor-efficient method for growers to use. Note that the highest treatment of GA, 1000 mg/l (1000 ppm), was not high enough to determine peak and toxicity levels, indicating that phacelia may respond to higher levels of GA.
Abstract 18219: Lack of Impact of Automated Referral on Attendance at Cardiac Rehabilitation Among Coronary Artery Bypass Grafting Patients
Authors: Billie-Jean Martin, Trina Hauer, Merill L Knudtson, Ross Arena, Leslie D Austford, James A Stone, Sandeep Aggarwal
Journal: Circulation (2012)

Introduction: Cardiac Rehabilitation (CR) is a guideline indicated modality for reducing residual cardiovascular risk among patients after they undergo Coronary Artery Bypass Grafting (CABG). Howev...
Phase I/II study of vandetanib for patients with recurrent malignant gliomas.
Authors: K. A. Mcnicol, T. N. Kreisl, F. M. Iwamoto, J. Sul, H. A. Fine
Journal: Journal of Clinical Oncology (2010)

2083 Background: EGFR and VEGFR signaling have been implicated in the development and growth of glioblastoma, and simultaneous inhibition of both of these signal transduction pathways has the potential to be a more effective therapeutic approach than inhibiting a single pathway. Vandetanib is an inhibitor of VEGFR-2 and EGFR tyrosine kinase activities, which has previously been shown to have anti-tumor activity in histologically diverse pre-clinical models of human cancer, including subcutaneous and orthotopic models of human glioma. Methods: A phase I study evaluated the MTD of vandetanib in patients on enzyme-inducing antiepileptics (EIAEDs). Eligibility criteria were histologically proven glioblastoma (GBM), anaplastic glioma (AG), progressive low-grade glioma (LGG), or radiographically diagnosed brainstem gliomas, radiologic progression after RT, age ≥ 18, KPS ≥ 60, and adequate bone marrow and organ function. There was no limit on the number of prior relapses or chemotherapies. Doses were escalated on a 3 + 3 design, with dose levels of 300, 400, 500, 700, and 900 mg QD. MTD was defined as the highest dose with DLTs in 1/6 or fewer patients. In phase II, patients with histologically proven AG were eligible, with other eligibility criteria as outlined above. Patients on EIAEDs were excluded from the phase II study. Patients received vandetanib 300 mg QD on 4- week cycles. Primary endpoint was PFS6. Results: In phase I, 15 patients were evaluated (8 GBM; 5 AG, 2 LGG). Median age 44 (18-66); median KPS 90 (80-100); median prior chemotherapies 1 (1-5). The MTD was determined to be 400 mg. There was 1/6 DLT (grade 3 rash) at this dose. At 500 mg there were 2/6 DLTs; one grade 3 prolonged QTc, and one grade 4 DVT/PE. In the phase II trial, there were 32 patients with AG. Median age 41 (18-69), median KPS 90 (60-100), median prior chemotherapies 2 (0-6). There were 2 PRs, and 13 SDs. One patient remains progression-free on study for over 21 months. PFS6 was 13.2% (95% CI: 4.2-27.5%), and median PFS was 1.8 mo (95% CI: 0.89-2.66 mo). Median OS was 7.4 mo (95% CI: 3.9-12.5 mo). Conclusions: Vandetanib is well tolerated, with a MTD of 400 mg QD in patients taking EIAEDs. In patients not on EIAEDs, vandetanib 300 mg QD had only limited monotherapy activity in recurrent AG. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca