tbuckley/cabot-search huggingface dataset:
A phase I study of the novel molecularly targeted vascular targeting agent, Exherin (ADH-1), shows activity in some patients with refractory solid tumors stratified according to N-cadherin expression
Authors: D. J. Jonker, D. J. Stewart, R. Goel, L. Avruch, G. Goss, J. Maroun, C. Cripps, J. Wells, R. K. Malik, W. P. Peters
Journal: Journal of Clinical Oncology (2005)

3038 Background: Malignant transformation and invasive capacity is highly correlated with upregulation of N-cadherin, a cell adhesion molecule expressed on both tumor cells and vascular endothelium. ADH-1 is a cyclic pentapeptide (CHAVC) which competitively inhibits N-cadherin mediated endothelial cell, pericyte and tumor cell interaction resulting in rapid onset of tumor vascular angiolysis and apoptosis in preclinical models. We report safety and pharmacokinetics (PK) from the first human study. Methods: 33 patients with refractory solid tumors received 54 cycles of ADH-1 by bolus injection at 8 dose escalations from 50 to 840 mg/m2to define toxicities (AE) and maximum tolerated dose (MTD) stratified by cadherin status with N-cadherin positive (n=12), unknown (n=3) or negative (n=18) tumors. Dynamic MRI was performed in cohorts 3 to 8 where feasible to assess tumor perfusion changes. Results: MTD has not been reached. The most common AEs were grade 1–2 nausea (27%), fatigue (58%), hot flushes (15%) and dysguesia (24%). AEs > grade 2 possibly or probably drug related include pain at sites of tumor (n=3), erectile impotence (n=1), brief post-infusion chest discomfort, flushing, and EKG ST changes in 1 patient, without sequelae, not recurring with slower infusion (n=2). One coronary syndrome occurred in a patient with pretreatment abnormal EKG and previously unknown 99% LCX occlusion. PK data show that mean half-life increases from 1.4 hours below 300 mg/m2 to 2.9 hours at higher doses. No clinical activity has been seen in N-cad -ve patients to 840 mg/m2. Three patients with N-cad +/unk tumors showed antitumor activity. A patient with a chemotherapy refractory N-cad +ve squamous cell esophageal cancer rapidly achieved PR sustained through 6 cycles of treatment. A Cushingoid patient with highly refractory adrenal cancer has received 5 doses of ADH-1 (4 doses in special access) with normalization of marker cortisol levels after each administration. A NSCLC patient had a mixed response. Conclusions: ADH-1 has been well tolerated at the doses given. MTD has not been reached. Evidence of anti-tumor activity has been noted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Adherex Technologies Adherex Technologies Adherex Technologies Adherex Technologies
Intra-arterial, abdominal chemoperfusion with chemofiltration in the treatment of progressive stage IV gastric cancer.
Authors: Andreas Sendler, Karl R. Aigner
Journal: Journal of Clinical Oncology (2015)

141 Background: Treatment of patients (pts.) with progeressive stage IV gastric cancer remains a therapeutical problem. Survival of the pretreated pts. is low and the therapeutic options are sparse. In this situation, locoregional therapeutic strategies could be an option. Methods: 28 pretreated pts. (17 male, 11 female, mean age 59 y.) after resection and at least second line systemic chemotherapy were included in a phase II study of isolated abdominal perfusion and subsequent chemofiltration. All pts. had liver metastases (mets.), 50% (n = 14) had peritoneal carcinomatosis with malignant ascites. No pat. had cerebral, pulmonal or bone mets.. After insertion of a venous and arterial 21 ch. stop flow catheter via a femoral access, the v. cava was blocked beneath the right atrium, the arterial catheter was blocked above the celiac trunk. The thighs were blocked by pneumatic cuffs. Chemotherapy consisted of 35 mg/m 2 cisplatinum, 20 mg/m 2 adriamycin and 12 mg/m 2 mitomycin q 3 weeks till progress or dead. The agents were administered via the arterial access, followed by 15 min of hypoxic abdominal perfusion via an external pump, followed by chemofiltration for 45 min. The procedure was done under general anaesthesia. Primary endpoint of the study were overall survival, secondary endpoint was control of the ascites. Results: A total of 92 cycles (mean 3.25) were administered. Toxicity was low with leucopenia CTC grad I in 9 pts., gastrointestinal disorders grad II in 8 pts. and surgical complications grad II in 40 % of the pat. (lymphatic fistula). In 9/14 (65%) of pts. with ascites, the ascites was at least controlled or vanished. One year survival was 28.6% (Kaplan-Meier), 2 year survival was 11.4%. Median survival was 6 months. Conclusions: Intra-arterial, isolated abdominal chemoperfusion with consecutive chemofiltration in heavily pretreated patients with gastric cancer metastasized to the abdominal cavity is a valuable option for palliative treatment with low side effects. In 65% of the affected pts., malignant ascites was controlled sufficiently, ameliorating the quality of life.
Third generation oral contraceptives and risk of myocardial infarction: an international case-control study
Authors: M. A Lewis, W. O Spitzer, L. A J Heinemann, K. D MacRae, R. Bruppacher, M. Thorogood
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To test whether use of combined oral contraceptives containing third generation progestogens is associated with altered risk of myocardial infarction. <b>Design</b>: Matched case-control study. <b>Setting</b>: 16 centres in Austria, France, Germany, Switzerland, and the United Kingdom. <b>Subjects</b>: Cases were 153 women aged 16-44 with a myocardial infarction event. Controls were 498 women (at least 3 controls per case) unaffected by myocardial infarction who were matched with their corresponding case for age and for hospital or community setting within four months of the index infarction. <b>Main outcome measures</b>: Odds ratios derived with stratified analyses and unconditional logistic regression to adjust for potential confounding variables. <b>Results</b>: The estimated odds ratio for myocardial infarction of third compared with second generation oral contraceptives among all 651 study subjects was 0.36 (95% confidence interval 0.1 to 1.2) (P=0.11). The odds ratio for the United Kingdom and Germany alone was 0.45 (0.1 to 1.8) (P=0.26). Other odds ratios for the five countries were 3.1 (1.5 to 6.3) (P=0.003) for use of second generation products v no current use and 1.1 (0.4 to 3.4) (P=0.9) for use of third generation products v no current use. Among the confounding variables the independent contribution of smoking (for which adjustment was made in the above estimates) proved to be important (10.1 (5.7 to 17.9), P&lt;0.001). <b>Conclusion</b>: An odds ratio of 0.45 with wide confidence intervals shows that third generation oral contraceptives compared with second generation products are associated with a reduced risk of myocardial infarction or with no difference. This finding from an interim analysis should be interpreted with extreme caution. However, the excess risk of venous thromboembolism associated with the use of third generation products may be balanced by the reduced risk of myocardial infarction associated with the same products. <h3>Key messages</h3> Key messages Compared with the results of British studies published in the 1970s, the risk of myocardial infarction among current users v non-users of second generation oral contraceptives was low The risk of myocardial infarction was appreciably lower among women using third generation products, the risk being comparable to that among women who did not use oral contraception and two to three times lower than that among women using second generation products The results suggest that about 12 fewer deaths from myocardial infarction in England and Wales and 46 fewer in Germany would occur each year if all those taking second generation oral contraceptives started taking third generation products Both the risks and the benefits of oral contraceptives need to be considered in a balanced way so that doctors can give judicious advice and women have informed choice
Quality of life in survivors of chemoradiation of the cervix.
Authors: F. H. Vaz, M. Ribeiro, A. Opiniao, N. Asensio, M. Roldao, A. Francisca, J. Oliveira, A. Miranda
Journal: Journal of Clinical Oncology (2010)

e15514 Background: Chemoradiation of the cervix is the standard treatment for locally advanced disease. The data concerning survivors of cervix chemoradiation are scarce. Our objective is to study quality of life (QoL) in these patients using a validated scale. Methods: Design: case-control study. Case group: All (135) cervical cancer survivors treated with chemoradiation, from November 2000-September 2002, in our Institute. All pts included were required to have a minimum follow up without relapse of 18 months. Women were contacted by telephone and invited to participate in the study. Control group: healthy women matched for age were recruited in the Breast Cancer Evaluation Clinic of our institution. The questionnaire was self-administered. Instruments: The Portuguese translated and validated version of the Functional Assessment of Chronic Illness Therapy-Cervix Cancer Questionnaire (FACT-Cx, 4th version) was used. This scale combines a Global QoL assessment (FACT-G) and a Cervix Cancer subscale (CxCs). A trial outcome index (TOI) combines the CxCs with the Physical (PWB) and Functional (FWB) well-being subscales of FACT-G. The other FACT-G subscales are Emocional (EWB) and Social well-being (SWB). Results: From 135 eligible pts, 69 cases (51%) agreed to participate in the study and 69 controls were also recruited. Preliminary analysis: median age for cases and controls is 56 (37-81) and 53.5 (34-74) respectively. Medium follow-up for cases is 40.6 months (20.8-58.2). FACT-G total score was 77.98 and 79.65 for cases and controls respectively (p = 0.63). FACT-G subscales (Cases vs Controls): PWB- 22.48 vs. 23.95 (p = 0.1) SWB: 19.77 vs. 18.58 (p = 0.86); EWB- 17.47 vs.17.52 (p = 0.94) and FWB-18.29 vs. 19.12 (p = 0.39). FACT-Cx total score: 40.30 vs. 43.32 (p = 0.03) and FACT-Cx TOI score: 81.08 vs 86.97 for cases and controls respectively (p = 0.03). Conclusions: General quality of life of our cases was not significantly different from the control group (including specific subscales). However when considering disease-specific scales cervix cancer survivors treated with chemoradiation showed significantly worse QoL than controls. No significant financial relationships to disclose.
Ten-year breast cancer survival - at what cost in human and physical terms? A case-control study of long-term survivors of breast cancer and their physical and functional well-being
Authors: M. E. Trudeau, L. Lickley, S. Narod, S. Mergler, G. Hawker, C. Sawka, D. Lee
Journal: Journal of Clinical Oncology (2004)

8010 Background: We sought to clarify the long-term side effects of treatment and quality of life (QOL) of breast cancer survivors. Methods: We conducted a case-control study of survivors, ≤ 10 years disease-free since diagnosis, matched to women with benign breast disease for age, years followed, and demographic profile. Data was collected for routine blood tests, lipids, bone mineral density (BMD), exercise step test, HRT use, vitamin and alternative medication (AM) use, arm strength and measurements, health history, and for survivors, breast cancer demographics. QOL instruments included EORTC QLQ-C30, SF36, and QOL-CS. Results: N = 850, 425 cases, 425 controls. For cases, average tumour size was 2.2 cm, 57% ER +, 40% PR +. 93.8% had axillary nodal dissection, 24.1% had positive nodes, median of 11.8 nodes removed, median of 1 positive. 59.7% had lumpectomy, 50.8% radiotherapy, 33% tamoxifen, 4.9% ovarian ablation, 22.8% chemotherapy, and 13% breast reconstruction. Cases had significantly more pack years smoked (p = 0.04), higher cholesterol (p = 0.01), triglycerides (p = 0.02), LDL (p = 0.04), cholesterol/HDL ratio (p < 0.001); and significantly less arthritis (p = 0.01), GI (p = 0.01) and GU (p = 0.006) complaints, and HRT use (p < 0.0001). BMD was not different. Controls used significantly more AM, cases more mental imagery (p = 0.0002). Cases had significantly larger arm circumferences (p = 0.002), decreased handgrip strength (p = 0.04), controlled for dominant arm and side of surgery. SF 36: social functioning was better for controls (p = 0.03) and role-emotional (p = 0.03). EORTC-QLQ-C30: controls had more pain (p = 0.05), cases had financial difficulties (p = 0.04). QOL-CS: controls had better psychological (p<0.0001) and social functioning (p<0.0001), cases were more spiritual (p<0.0001). Conclusions: Breast cancer survivors had significantly increased arm circumferences, decreased handgrip strength, elevated lipids, decreased psychological and social functioning, but improved spirituality. No significant financial relationships to disclose.
Interactions of risk factors in predicting suicide
Authors: M A Young, L F Fogg, W A Scheftner, J A Fawcett
Journal: American Journal of Psychiatry (1994)

The authors examined interactions among risk factors for suicide, a strategy not typically followed in suicide research. Their results suggest an explanation for gender differences in suicide rates and qualifications in the relationship between hopelessness and suicide based on history of drug and alcohol abuse.
Abstract 14031: Postural Orthostatic Tachycardia Syndrome With Associated Gastrointestinal Symptoms in Children; Is There an Underlying Neuropathic Substrate?
Authors: Jeffrey P Moak, Robin R Fabian, Lindsay C Clarke, Anil Darbari
Journal: Circulation (2013)

Introduction: Postural orthostatic tachycardia syndrome (POTS) results in multiple organ system symptoms. While the etiology for cardiovascular symptoms seems straightforward, the underlying pathop...
Identifying low-risk febrile neutropenic cancer patients in the West of Scotland
Authors: Y. C. Drew, R. Appleton, R. Jordan, J. White, J. Paul
Journal: Journal of Clinical Oncology (2006)

18592 Background: Febrile neutropenia (FN) is a potentially life threatening complication of chemotherapy. In-patient treatment using intravenous antibiotics reduces FN related mortality. However, most patients with FN are at low risk of complication. Identifying them could result in new strategies such as out-patient, oral antibiotic, based treatment resulting in improved quality of life and cost savings. The Multinational Association for Supportive Care in Cancer (MASCC) and the Talcott model were developed to identify such patients. Two randomised controlled trials have shown that oral antibiotics in low risk patients are safe and effective. However are such models appropriate in populations with a high incidence of co-morbidity such as the West of Scotland? This study reviews FN admissions to our cancer centre to determine the proportion of patients that would fall into a low risk group according to the MASCC and/or Talcott models and to identify other factors that might predict for low risk. Methods: Review of FN admissions between June–December 2002. Data included: patient demographics, MASCC score, Talcott group, co-morbidity, haematological and biochemical values, prior use of antibiotics and growth factors (GFs) and whether the fever resolved without serious medical complication (FRWMC). Results: 77 episodes of FN involving 68 patients. Mean age = 51 (range 16–79). 94% involved patients with solid malignancies. Commonest tumour type was breast (29%). Patients were classified as MASCC and Talcott low risk in 52% and 31% of episodes respectively. There was a significant association between low risk MASCC score and low risk Talcott score (χ 2 28.665, d.f.3, p &lt; 0.001). Low risk MASCC was associated with FRWMC (χ 2 4.193, d.f.1, p &lt; 0.05). Multiple logistic regression of risk factors showed that high bilirubin and low albumin were associated with a worse outcome. FN mortality rate was 7.8%. Conclusions: The use of clinical risk models to identify low risk patients can predict for an uncomplicated recovery in our patients. Bilirubin and albumin values at presentation added predicted value for low risk over and above the MASCC model. Future trials may validate this observation. No significant financial relationships to disclose.
Combining galiximab with the chemotherapeutic agents fludarabine or doxorubicin improves efficacy in animal models of lymphoma
Authors: H. K. Hariharan, T. Murphy, D. Clanton, L. Berquist, P. Chu, T. Yun, A. Molina, S. Ho
Journal: Journal of Clinical Oncology (2007)

3040 Background: Galiximab, a primatized monoclonal antibody that binds with high affinity to CD80 and mediates antibody- dependent, cell-mediated cytotoxicity in vitro, is currently under investigation for the treatment of follicular non-Hodgkin’s lymphoma (NHL). In a phase I/II monotherapy study, galiximab produced an overall response rate of 11%, and tumor reductions were observed in 46% of patients. Initial clinical trials also demonstrate that galiximab is well tolerated and suggest that combining galiximab with rituximab (anti-CD20) provides clinical benefit. These results are consistent with preclinical studies in murine lymphoma xenograft model systems, which demonstrate the superiority of combination therapy. Methods: To further define the therapeutic potential of galiximab, the Raji subcutaneous and the SKW disseminated lymphoma murine xenograft models were used to define the in vivo efficacy of galiximab alone or in combination with fludarabine or doxorubicin. Similar studies were performed with rituximab. Results: In the Raji model, both galiximab and rituximab exhibited maximal inhibition of the growth of preestablished (150-mg) tumors at a dose of 3 mg/kg/wk. Interestingly, higher doses of galiximab (but not rituximab) showed reduced inhibition. Galiximab (3 mg/kg/wk) inhibited tumor growth alone (P&lt;0.0001 vs. control) and showed significantly enhanced activity when combined with fludarabine (50 or 100 mg/kg daily for 5 days; P&lt;0.0002 vs. galiximab alone and P&lt;0.003 vs. fludarabine alone). Similar results were observed with rituximab. In the SKW model, treatment with galiximab (5 mg/kg/wk for 6 doses) significantly enhanced survival compared with a control (P&lt;0.0001) or doxorubicin (2.5 mg/kg/day for 3 doses; P&lt;0.0001). Studies combining fludarabine or doxorubicin with both galiximab and rituximab are ongoing. Conclusions: Studies in animal models of lymphoma indicate that galiximab may provide clinical benefit when used in combination with chemotherapeutic agents such as fludarabine and doxorubicin, and provide a rationale for the investigation of these novel chemoimmunotherapy combinations in clinical trials. No significant financial relationships to disclose.
Impact of reduced dose intensity of adjuvant bolus 5-FU based chemotherapy for stage 2 and 3 colon cancer
Authors: S. Yu, S. O’Reilly, S. Gill
Journal: Journal of Clinical Oncology (2005)

3664 Background: Adjuvant 5-FU based therapy (AT) improves survival for patients with resected high-risk colon cancer. The impact of AT dose intensity on outcomes has not been previously examined. Methods: Patients with resected stage 2 or 3 colon cancer who initiated 5-FU/Folinic Acid (FA) (375–425mg/m2 of 5-FU with 20mg/m2 FA for 5 consecutive days every 28 days) between June 1998 and December 1999 were identified through the BC Cancer Agency patient registry and pharmacy database. Patient records were retrospectively reviewed. Dose intensity (DI) was calculated based upon: (actual dose delivered/expected full dose) divided by (actual number of days of treatment/expected number of days of treatment). Patients were divided into two cohorts: A - Greater than 85% of planned DI received or B - Less than or equal to 85% of planned DI received. Patient characteristics and survival (by the Kaplan-Meier method) were compared in both cohorts. Results: One hundred and thirty six patients were eligible for review. Median follow-up was 59.2 months. Cohorts A and B are compared in Table 1. Patients in cohort B (reduced DI) were more likely to be older, female and have stage III disease, although these differences were not statistically significant. Overall survival between the two cohorts was similar. Conclusions: In general practice, dose reductions are common among patients receiving adjuvant bolus 5-FU/FA chemotherapy for colon cancer. However, reduced DI does not appear to adversely impact long-term survival. No significant financial relationships to disclose.
Differential expression of CA125 and a novel serum tumor marker HE4 in epithelial ovarian cancer
Authors: A. Brown, C. Miller, K. Robison, E. Somers, J. Allard, C. O. Granai, S. Skates, R. C. Bast, R. G. Moore
Journal: Journal of Clinical Oncology (2008)

5533 Background: The serum tumor marker CA125 is an excellent marker for determining response to treatment and for the detection of early recurrence of disease in patients with epithelial ovarian cancer (EOC). However, twenty percent of all epithelial ovarian cancers do not produce CA125 and therefore it is not a useful marker for these patients. The novel serum tumor marker HE4 has been shown to be elevated in EOC. The objective of this study was to examine the differential expression of HE4 compared with CA125 in EOC. Methods: This was a multicenter prospective trial with IRB approval at each site. All patients gave full informed consent prior to collection of blood samples and surgery. All blood samples were collected prior to surgery and all patients had full surgical staging. Serum tumor marker levels were measured with a CanAg HE4 EIA and a CanAg CA125II EIA assay kit. All cases were reviewed by a gynecologic pathologist through a central pathology review. Results: There were 566 patients enrolled onto trial of which 151patients were diagnosed with cancer with 129 being an EOC (83 serous, 16 endometrioid, 6 mucinous, 6 clear cell, 5 undifferentiated, 8 mixed, 3 MMMT and 1 adenosquamous and 1 transitional cell) and 22 LMP tumors of the ovary (14 serous, 7 mucinous and 1 endometrioid). Analysis of CA125 and HE4 together showed that at least one of the markers was elevated in 87% (131/151) of all cases (LMP and EOC) and in 91% (117/129) of EOC cases. CA125 alone was found to be elevated (>35 IU) in 79% (120/151) of all cases and in 82% (106/129) of EOC cases. HE4 was found to be elevated (>140pM) in 71% (107/151) of all cases and in 80% (103/129) of EOC cases. In cases where CA125 was not elevated HE4 was elevated in 35% (11/31) of all cases and 48% (11/23) of EOC cases. When HE4 was not elevated CA125 was elevated in 55% (24/44) of all cases and 54% (14/26) of all EOC cases. Conclusions: The serum tumor marker HE4 is an excellent marker for EOC and in combination with CA125 one of these markers will be elevated in greater than 90% of all EOC cases. When CA125 levels are normal HE4 is elevated in half of these cases. HE4 complements CA125 as a serum tumor marker for EOC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Fujirebio Diagnostics Inc. Fujirebio Diagnostics Inc. Fujirebio Diagnostics Inc. Fujirebio Diagnostics Inc. Fujirebio Diagnostics Inc.