tbuckley/cabot-search huggingface dataset:
Safety of an intravenous (i.v.) dose of ibandronate followed by daily oral dosing in metastatic bone disease: Results of an open-label study
Authors: J.-J. Body, M. Lichinitser, N. Andreeva, M. Budde, B. Bergström
Journal: Journal of Clinical Oncology (2004)

735 Background: Ibandronate is a highly-potent aminobisphosphonate for the prevention of skeletal events from metastatic bone disease. A 3-month trial has assessed the safety and effects on bone turnover of a single rapid infusion of i.v. ibandronate, followed by daily oral dosing. This abstract reports the safety results. Methods: In a multicenter, open-label study of patients with metastatic bone disease from breast cancer or multiple myeloma, a single i.v. dose of ibandronate (6mg infused over 15 minutes) on Day 1 was followed by oral ibandronate 50mg/day for 12 weeks. The combination of an initial i.v. dose with subsequent daily dosing was adopted to promote rapid onset of the effects on bone turnover. Adverse events (AEs) were recorded during the course of the study and safety laboratory assessments included the monitoring of serum creatinine levels. Results: Thirty-nine patients were included in the safety analysis. On Day 1, 3 patients reported non-serious AEs that were considered possibly or probably related to ibandronate infusion (flu-like syndrome, asthenia, headache and cervical pain). During the 12-week treatment period, 25 patients experienced at least one AE. The most common AEs reported, but not necessarily related to ibandronate, were nausea (n=6), asthenia (n=5), raised temperature (n=3) and bone pain (n=3). Four patients were withdrawn due to AEs prior to completion of the 12-week study. Two patients experienced serious AEs, of which only one was considered related to ibandronate (stomach ulcer, in a patient with a medical history of gastritis). No renal AEs were reported, and calculated creatinine clearance levels were similar at baseline and week 12 (mean 77.9 ± 22.4μmol/L vs 79.4 ± 25.8μmol/L). Conclusions: A single dose of i.v. ibandronate 6mg, followed by oral ibandronate 50mg/day for 12 weeks, was well tolerated in metastatic bone disease from breast cancer or multiple myeloma, with no significant changes in renal functioning. The 15-minute infusion schedule in this study was well tolerated and had no negative impact on renal safety. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Pharmaceuticals Roche Pharmaceuticals Roche Pharmaceuticals Roche Pharmaceuticals F. Hoffmann La Roche
Oncology beyond the hospital: 7 years taking care of cancer patients from the very begining until the last consequences.
Authors: Alberto Jacobo Cunquero Tomas, Claudio Dario Avila Andrade, Ferri Pep, Lauren Condori Farfan, Amaya Belen Fernandez Diaz, Ihsan Shaheen, Marina Meri Abad, Adriana Fernandez, Ana Blasco, Alfonso Berrocal, Maria Jose Safont, Cristina Caballero, Vega Iranzo, Maria Jose Godes, Carlos Camps
Journal: Journal of Clinical Oncology (2017)

75 Background: Comprehensive and continuous care is esential for the correct management of cancer patients. To achieve this, specific programs for early diagnosis and long survivor care are needed. Since 2007, within the project “Oncology beyond the Hospital: Oncologic assistance at the Universitary General Hospital of Valencia”, the Oncologist Liaison was created. Methods: Two tracks were designed: High-resolution track for patients with suspicion of non-diagnosed cáncer; and Oncologist Liaison track, to organize the follow-up of cáncer long survivors. We present a descriptive and retrospective study by reviewing medical records of patients referred to the high-resolution diagnostic consultation; and long survivors followed up by the Oncologist Liaison from May 2007 to September 2015 (2016 data under review). Results: High-resolution track: 1,596 patients with suspected cancer were visited. The mean time between the primary care physician consultation and the oncologist visit was 4.32 days. Main reasons for consultation were: breast disease (25.4%), blood test disorders (16.4%), enlarged lymph nodes (11.1%) and radiological suspicion of tumor (12%). 424 cancers were diagnosed (26.5%) all having been studied in Oncologic Committee: 22.6% lung; 17% lung; 16.2% breast; 11.8% lymphomas; 12.5% superior dighestive tract; and19.8% miscelanea. Long-survivors track: 1406 patienst free from disease were referred for surveillance of recurrence and treatment sequelae: 44% breast; 20% gastrointestinal; 17% gynecological; 7% double neoplasia; 4% of lung cancer and other tumors, 8%. Conclusions: With the integration of the Oncologist Liaison in the continuum of care, we have achieved: Normalization of oncologic approach among patients and primary care physicians; implementation of a fast-track for patients with cancer suspicion: access to the oncologist in less tan a week; case study in the Oncologic Comittee in the following week; and consensus in diagnosis and treatment plan in each case. Ensure control over long-survivors.
Optimized phase I-II trial design for vaccination with epidermal growth factor (EGF): Effect on immunogenicity and safety
Authors: E. Neninger, G. Gonzalez, T. Crombet, G. Fleites, I. Leonard, M. Gonzalez, T. Badia, A. Lage
Journal: Journal of Clinical Oncology (2004)

2610 Background: We have previously studied immunogenicity and safety of vaccination with EGF on advanced NSCLC patients. More than 70 patients were immunized in several pilot clinical trials. Here we present the preliminary results from a Phase I-II clinical trial in which we optimized the immunization protocol to improve vaccination effects. Methods: Immediately after diagnosis, 16 stages IIIb and IV NSCLC patients were enrolled in the trial. Each vaccination comprised a total dose of 200 ug (EGF) divided in 4 immunization sites. Vaccinations were administered on days 0 and 14. Chemotherapy (4–6 cycles of cisplatin-based regime) was initiated 14 days after the 2nd vaccine dose. Vaccinations continued on day 32 after the completion of chemotherapy and then monthly. The vaccine was composed of human recombinant EGF conjugated to P64K as carrier protein and emulsified in Montanide ISA51 (adjuvant). Sera anti-EGF antibody (Ab) titers as well as plasma EGF concentration ([EGF]) were measured monthly. Results: The EGF vaccine administered according to the protocol described above provoked improved antibody responses when compared with results obtained in previous trials. The geometric mean of maximal antibody titers was 38,054, which is more than 10 times that previously obtained. One hundred percent of patients seroconverted and 89% were good antibody responders. Immunogenicity descriptors also improved as compared with previously reached values. The Ab titers did not decrease during chemotherapy. The [EGF], after the 2 first immunizations, reached mean values of 8.6 pg/ml, which is less than half of the concentrations obtained in other trials. These low [EGF] levels were maintained during the follow-up period. The vaccination was safe and no serious related adverse events were observed. Conclusions: The described EGF vaccination protocol was safe and provoked an important improvement on immunogenicity descriptors. The administration of two doses of the vaccine prior to first line chemotherapy allows high antibody titers to be maintained as well as very low levels of [EGF], even after the immune suppression provoked by chemotherapy. No significant financial relationships to disclose.
Tamoxifen related uterine sarcoma - A retrospective review
Authors: J. A. Wernberg, J. L. Hoehn
Journal: Journal of Clinical Oncology (2004)

801 Background: Tamoxifen has been shown to significantly reduce the risk of tumor recurrence in women with receptor-positive breast cancer and has been used for chemoprevention in women with non-invasive cancer and women at high risk of developing breast cancer. One established and accepted risk with this treatment is the increased risk of uterine malignancy. Originally this was felt to be limited to endometrial adenocarcinoma, but recent evidence suggests an increased risk of uterine sarcoma as well. Methods: A 42-year retrospective review was performed at a rural tertiary care center. The charts of all patients with a diagnosis of uterine sarcoma were reviewed. 136 patients with uterine sarcoma were identifed. Any women with a primary diagnosis of breast cancer or use of tamoxifen for adjuvant or preventive therapy were substratified. Results: Of the 136 women with uterine sarcoma, ten patients had primary breast malignancies. Six of these ten women had received a five-year course of tamoxifen prior to the development of uterine sarsoma; four did not receive adjuvant hormonal therapy. Additionally, one of our patients enrolled in the National Surgical Adjuvant Breast and Bowel Project (NSABP) Breast Cancer Prevention Trial developed a malignant mixed mullerian tumor (MMMT) 27 months after completing a five-year course of tamoxifen. Conclusions: We therefore report seven cases of uterine sarcoma occurring subsequent to 60 months of tamoxifen treatment. This is compared to the report of 12 cases identifed from the NSABP treatment and prevention trials secondary malignancy data. We suggest that there may be a higher incidence of uterine sarcoma in tamoxifen-treated patients than that based on the NSABP data. Given the increased risk of uterine malignancy (both adenocarcinoma and sarcoma), as well as other potential complications of tamoxifen use, consideration needs to be taken before beginning hormonal therapy, especially in a prevention setting. No significant financial relationships to disclose.
Abstract 17311: Molecular Memory and the Epigenetic Regulation of Cardiac Intracellular Matrix Metalloproteinase-2
Authors: David H Lovett, Stanley Luk, Lalita Uttarwar, Sunil Joshi, Robert L RAffai
Journal: Circulation (2015)

Introduction: We have identified an intracellular isoform of MMP-2 generated by oxidative stress activation of a promoter in the first intron of the MMP-2 gene. This generates a N-terminal truncated isoform of MMP-2 (NTT-MMP-2) which is enzymatically active and found in mitochondria. NTT-MMP-2 triggers the mitochondrial permeability transition leading to myocyte regulated necrosis and inflammation. We hypothesized that transient oxidative stress induces durable epigenetic changes in the NTT-MMP-2 alternate promoter resulting in enhanced injury in subsequent episodes of stress (molecular memory). Methods: The intronic promoter was mapped using a combination of PCR-based and intronic/luciferase constructs. In vivo studies used the hypomorphic ApoER61h/h SR-B1-/- murine model (HypoE mice) of diet-induced coronary atherogenesis and myocardial infarction. Chromatin immunopreciptation (ChIP) probed the RNA Pol II, H3K4Me1 and H3K27Me3 epigenetic marks. NTT-MMP-2 was measured by qPCR. Results: NTT-MMP-2 transcription start sites were mapped to two stress-activated basal promoters along with a stress-activated NF-κB enhancer element. HypoE mice were fed a high fat diet (HFD) for 20 days, followed by gene repair of the hypomorphic ApoE alleles and returned to normal diet for 6-15 weeks. NTT-MMP-2 expression at 20 days of HFD was elevated two-three fold as compared to controls, remained elevated after 6 weeks of normal diet and returned to baseline at 15 weeks. ChIP of the intronic promoter revealed association of RNA Pol II at 6 weeks of normal diet and was not detectable at 15 weeks. In contrast, the pro-transcriptional mark H3K4Me1 remained elevated out to 15 weeks; the inhibitory H3K27Me3 mark returned to baseline at 15 weeks. A brief return to HFD (7 days) at 6 weeks increased NTT-MMP-2 expression resulting in myocyte inflammation and necrosis relative to controls exposed to only 7 days of HFD. Conclusions: Transient periods of oxidative stress lead to durable epigenetic changes in the NTT-MMP-2 promoter that facilitate exaggerated responses to otherwise minor levels of oxidative stress. Our findings may provide an explanation for the enhanced injury susceptibility to relatively minor stresses of patients with pre-existing cardiac disease.
Costs of potentially preventable emergency department use during cancer treatment: A regional study.
Authors: Laura Panattoni, Catherine R. Fedorenko, Karma L. Kreizenbeck, Stuart Greenlee, Julia Rose Walker, Mikael Anne Greenwood-Hickman, Sarah Barger, John Whitelaw Rieke, Ted Conklin, Sharon Chance, Keith D. Eaton, Rose Guerrero, Mary Gunkel, Renato G. Martins, Marilyn Moorhouse, Bruce Smith, Gary H. Lyman, Scott David Ramsey
Journal: Journal of Clinical Oncology (2017)

2 Background: There is growing recognition that many emergency department (ED) visits during cancer treatment may be related to poorly controlled disease or treatment-related symptoms and could be prevented. An RCT using the Symptom Tracking and Reporting (STAR) tool for proactive symptom management decreased the percentage of patients admitted to the ED (34% vs. 41%; p=0.02). Little is known about the costs of potentially preventable ED visits in a community setting. This study examined the number and costs of ED visits and their associated diagnoses. Methods: Cancer registry records for patients in Western Washington from 2011 to 2015 were linked with claims from two regional commercial insurers. Patients diagnosed with a solid tumor and treated with chemotherapy or radiation were selected. All ED utilization was tracked for 1 year after the start of treatment. ED-related diagnoses codes were labeled “Potentially Preventable” (PP) if they mapped to the 13 symptom categories targeted by STAR (e.g. pain, nausea) and non-PP otherwise. Costs of ED visits were inflation-adjusted and include claims with ED-related procedure, revenue, and place of service codes. All subsequent inpatient costs were excluded, likely under-estimating total costs. Results: Of the 7,075 eligible patients, 2,543 (35.9%) visited the ED an average of 1.79 times. Pain (720 visits), Dyspnea (279 visits), and Nausea (232 visits) were the most common potentially preventable diagnoses; Hypertension (506 visits), Fever (230 visits), and Diabetes (215 visits) were the most common non-PP diagnoses. $1,134,254 (25.2% of the total ED costs) was spent on PP ED visits. Of PP ED visits 20.3% (178/875) resulted in an inpatient stay. Conclusions: In our community setting, at least one quarter of ED costs were potentially the result of poor symptom management. An investment in better symptom management has a significant opportunity to both improve cancer care and lower total costs.[Table: see text]
SWOG 0019: A phase II study of gemcitabine and irinotecan for patients with untreated extensive stage small cell lung cancer (SCLC)
Authors: W. L. Akerley, J. McCoy, P. Hesketh, J. Crowley, L. Kaye, D. Gandara
Journal: Journal of Clinical Oncology (2004)

7202 Background: Extensive stage SCLC is associated with short survival despite conventional therapy. Accordingly, integration of an active alternate, non-platinum or -etoposide containing regimen could prove beneficial. Methods: Patients with untreated, extensive stage SCLC with adequate organ function and PS=0–2 were accrued from 1/02–3/03 to a phase II trial of gemcitabine 1000 mg/m2 and irinotecan 100 mg/m2 given on days 1 & 8 of a 21 day cycle until disease progression (maximum= 6 cycles). Brain metastases were eligible if asymptomatic or previously radiated. Results: Data is available for 81 eligible pts. The median age was 64 yrs (range 42–85), 78 had measurable disease and 42 (52%) were female. Six cycles were completed by 28 (35%) pts. Some degree of diarrhea occurred in 46 (57%; Gr1=23, Gr 2=9, Gr 3=13 Gr 4=1). Other Gr 3–4 toxicities were ANC 19 (23%), Hb 7 (9%), PLT 6 (7%), febrile neutropenia 4 (5%), fatigue 9 (11%), nausea 7 (9%) and vomit 6 (7%). The preliminary response rate is 29% (95% CI=19–39). The median survival is 8.0 months and 31 (38%) pts remain alive. Salvage therapy and subsequent responses have been collected prospectively. Conclusions: This data, although preliminary, suggests low toxicity and low response rate, but a median survival that is not dissimilar from platinum and etoposide-based treatment. Further follow-up, subset analysis and salvage evaluation are necessary. No significant financial relationships to disclose.
Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism
Authors: David J. Stott, Nicolas Rodondi, Patricia M. Kearney, Ian Ford, Rudi G.J. Westendorp, Simon P. Mooijaart, Naveed Sattar, Carole E. Aubert, Drahomir Aujesky, Douglas C. Bauer, Christine Baumgartner, Manuel R. Blum, John P. Browne, Stephen Byrne, Tinh-Hai Collet, Olaf M. Dekkers, Wendy P.J. den Elzen, Robert S. Du Puy, Graham Ellis, Martin Feller, Carmen Floriani, Kirsty Hendry, Caroline Hurley, J. Wouter Jukema, Sharon Kean, Maria Kelly, Danielle Krebs, Peter Langhorne, Gemma McCarthy, Vera McCarthy, Alex McConnachie, Mairi McDade, Martina Messow, Annemarie O’Flynn, David O’Riordan, Rosalinde K.E. Poortvliet, Terence J Quinn, Audrey Russell, Carol Sinnott, Jan W.A. Smit, H. Anette Van Dorland, Kieran A. Walsh, Elaine K. Walsh, Torquil Watt, Robbie Wilson, Jacobijn Gussekloo
Journal: New England Journal of Medicine (2017)

The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition.
Early assessment of MCV to predict clinical outcome in patients with advanced gastrointestinal stromal tumors (GIST) receiving imatinib.
Authors: Anastasia Constantinidou, Dimitrios Krikelis, David Olmos, Michelle R. Scurr, Robin Lewis Jones, Sue Ashley, Ian Robert Judson
Journal: Journal of Clinical Oncology (2012)

10086 Background: In patients with advanced GIST, imatinib trough levels have been associated with a lower rate of clinical benefit. Anecdotal observations have suggested that commencing treatment with imatinib may be associated with an increase in red blood cell size as measured by MCV and MCH, indicating the effect of imatinib on KIT signalling in the bone marrow. Methods: In this retrospective review we examined a possible connection between changes in MCV and MCH after the first 3 months (mo) of treatment with imatinib and progression-free survival (PFS). Data for patients with inoperable advanced or metastatic GIST treated between 2000 and 2011 were available for analysis. Patients were categorised in quartiles according to the distribution of the percentage of change of MCV and MCH between start of imatinib (baseline) and 3 (+/- 0.5) mo (ratio %=MCV change at 3 mo/MCV at baseline). PFS curves were plotted using the Kaplan-Meier method and compared using the log rank test. Results: One hundred and thirty patients were eligible for analysis and the demographics were: male:female 84:46, median age at presentation: 60.5 (23.5-86.5) years, commonest primary tumour sites: stomach (72/130) and small bowel (44/130), commonest metastatic site: liver (76/130). In the patients with a 10% or over increase in MCV (p75-p100) at the 3 mo (+/-0.5) time point a significantly longer PFS was observed compared to those with a smaller magnitude of change (PFS of 37.1 mo vs 24.3 mo, p=0.032). A similar trend although not statistically significant was observed in patients with MCH of 15% or over (p75-p100) with PFS of 34.0 mo vs 25.8 (p=0.125). The two parameters (MCV and MCH) showed a high correlation of percentage change (r 2 =0.85). The patients with a 10% MCV increase and /or 15% MCH increase (total=40) showed a significantly longer PFS (34.0 mo) compared to those with lower percentage change (PFS= 24.3) p=0.035. Conclusions: Simple laboratory parameters may be indicators of imatinib pharmacokinetics and may therefore be used as surrogate markers of clinical outcome. Larger prospective studies are required to confirm the results of this study.
Second-line treatment of advanced urothelial cancer with paclitaxel and RAD001 (everolimus) in a German phase II trial (AUO trial AB 35/09).
Authors: Guenter Niegisch, Margitta Retz, Mark K. Thalgott, Stefan Balabanov, Friedemann Honecker, Michael Stöckle, Carsten Henning Ohlmann, Martin Boegemann, Frank vom Dorp, Juergen Gschwend, Arndt Hartmann, Christian Ohmann, Peter Albers
Journal: Journal of Clinical Oncology (2012)

4590 Background: Efficacy of second-line treatment after cisplatinum failure in patients (pts) with advanced urothelial cancer is limited. Based on encouraging preclinical data and results from several phase I trials in solid cancers, we evaluated the safety and efficacy of the combination of paclitaxel and RAD001 (everolimus) in these pts. Methods: In this single-arm, multicenter phase II trial, pts failing prior cisplatinum based combination treatment for advanced urothelial cancer were treated with paclitaxel (175 mg/m² i.v., three-weekly) and the mTOR-inhibitor RAD001 (10 mg p.o., once daily). Pts were treated until tumor progression by RECIST criteria or until a maximum of 6 cycles was completed. A one-stage design was used to evaluate the overall response rate (ORR) as primary endpoint. Results: 27 pts (18 men, 9 women; median age 63 (35-76) years; ECOG ≥ 1: 11/27pts, hepatic metastases: 10 pts, Hb&lt;10 g/dl: 8 pts; upper urinary tract: 9 pts, lower urinary tract 15 pts, both: 3 pts) were enrolled between 07/09 and 12/11. As of 01/12, 19 pts are evaluable for the primary endpoint and the toxicity profile (6 pts still on treatment, 1 patient has withdrawn consent). Main toxicities (all CTCAE grades) were anemia (10/19 pts), leucopenia (8/19 pts), and neuropathy (9/19 pts). Grade III/IV toxicities were anemia (4/19 pts) and leucopenia (4/19 pts). No treatment related deaths were observed. Median number of cycles was 4 (1-6). Complete remission (CR) and partial remission (PR) was observed in 0/19 and 3/19 pts, respectively (ORR 16%). Stable disease (SD) was observed in 10/19 pts. Median time-to-progression (TTP) was 2.7 months (95% confidence interval [CI] 1.6 – 4.4), median overall survival (OS) was 6.5 (CI 4.5 – 9.2) months. Conclusions: Frequency and severity of toxicities were acceptable. Using the combination of RAD001 and paclitaxel as second-line treatment for advanced urothelial cancer after cisplatinum-failure, response rates and survival times comparable to vinflunine were observed.