bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral treatment of metastatic breast cancer (MBC) with capecitabine (X): What influences the decision-making process?
Authors: Gornas M. , Szczylik C. 
Published: March 2020

1111 Background: MBC may be considered a chronic disease. Many treatments require frequent clinic visits or hospitalization. Oral X is active, well tolerated, and offers several opportunities per cycle for dose adjustment. This observational study assessed patient (pt) preferences determining treatment choice. Methods: Female MBC pts eligible for X answered a questionnaire about influences on their preference for oral therapy: desire to continue their job, possibility of staying at home during treatment, more convenient way of taking medication, medical contraindications for i.v. treatment, and/or contraindication for combination therapy. Data on medical history (stage, treatment, metastatic sites) were also collected. Results: 218 questionnaires were analyzed. Median age at diagnosis was 52 years (range 27–77). Prior therapy included neoadjuvant chemotherapy (CT; 32%), surgery (93%, including 5% breast-conserving), adjuvant CT (62%), adjuvant endocrine therapy (ET; =52%), and ET for MBC (48%). X was given 1st-line for MBC in 38 pts (17%), 2nd-line in 85 (39%), and =3rd-line in 95 (44%). The most common reason for choosing oral X was more convenient form of drug delivery (154/218; 71%). 147 pts (67%) gave >1 reason for choosing oral therapy. In pts with only one reason (n=71), the most common were possibility of staying at home during treatment (30/71; 42%) and more convenient form of drug (15/71; 21%). Pts receiving 2nd-line X preferred to receive drugs in a more friendly way (62/85; 73%) and stay at home during therapy (63/85; 74%). Corresponding values in pts receiving =3rd-line X were 68/95 (72%) and 53/95 (56%), respectively. Conclusions: MBC causes many psychologic and social problems. Pts prefer to receive drugs in a more friendly way at home. Therefore exploration and introduction of new, effective oral drugs into MBC treatment is vital. No significant financial relationships to disclose.
Renal safety of intravenous ibandronate 6mg infused over 15 or 60 minutes in patients with breast cancer and bone metastases: A randomized, open-label study
Authors: von Moos R. , Thürlimann B. , Caspar C. B. , Inauen R. , Greil R. , Schütz F. , Flores L. , Bergstrom B. , Schmieding K. , Pecherstorfer M. 
Published: March 2020

1114 Background: Clinical data show that a single 15-minute intravenous infusion of ibandronate (IA) 6mg is associated with no significant changes in renal functioning. The aim of this study was evaluation of renal safety of repeated 15-minute intravenous infusions of IA 6mg in women with breast cancer and bone metastases. Methods: Patients (n=127) were randomized to receive treatment with intravenous ibandronate as a 15-minute infusion (n=101) or as a 60-minute infusion (n=26) every 3–4 weeks. Patients were stratified according to previous treatment and the presence or absence of visceral metastases. All patients had serum creatinine within normal limits and calculated creatinine clearance =50mL/min as assessed prior to each infusion throughout the trial. The primary endpoint was the percentage of patients with an increase in serum creatinine from baseline of =44.2μmol/L (0.5mg/dL) at any point in the study. Results: Three percent of patients in the 15 minute infusion (3/101) met the primary endpoint with either hydronephrosis due to tumor, severe diarrhea or pre-existing diabetes with urinary tract infection. No patients in the 60-minute infusion arm (0/26) had an increase in serum creatinine that met the primary endpoint. No clinically relevant changes were seen in serum creatinine, calculated or measured creatinine clearance, or levels of N-acetyl-β-D- glucosaminidase, a1-microglobulin or microalbumin in either arm. There were no marked changes in mean bone pain or analgesic requirement scores. A slight increase in mean WHO performance status score was seen in both arms. Most adverse events were mild or moderate. No clinically-relevant mean changes were observed in vital signs, hematology, blood chemistry including renal function or urinalysis parameters. Renal impairment was related to IA in the 3 patients with increased serum creatinine. Conclusions: IA 6mg administered as a 15- minute intravenous infusion every 3–4 weeks had a renal safety profile consistent with that of the 60-minute infusion, suggesting that a 15-minute infusion of ibandronate 6mg is well-tolerated in patients with breast cancer and bone metastases. No significant financial relationships to disclose.
Metronomic chemotherapy with capecitabine and oral cyclophosphamide in combination with bevacizumab in metastatic breast cancer (mbc): Evidence of activity of an antiangiogenic treatment
Authors: Rocca A. , Dellapasqua S. , Pietri E. , Dettori M. , D’Alessandro C. , Ghisini R. , Colombo A. , Goldhirsch A. , Colleoni M. 
Published: March 2020

11501 Background: Metronomic chemotherapy has shown efficacy in patients (pts) with MBC. Laboratory and clinical studies suggest that the combination with a specific antiangiogenic drug may be particularly effective. Methods: We evaluated the activity and biological effects of low dose continuous oral Capecitabine (500 mg PO TID) and Cyclophosphamide (50 mg PO QD) plus Bevacizumab (10 mg/Kg Q 2 weeks) in a two stage phase II trial in MBC pts, who received =3 lines of chemotherapy for advanced disease. Planned sample size is 46 pts. Results: To date, 26 patients have been enrolled on the study and 23 are evaluable. Pts characteristics: 1/2/=3 sites of metastatic disease 6/9/11 pts; dominant sites of disease soft tissues/bone/viscera 1/11/22; previous treatment for MBC: endocrine/chemo/trastuzumab 13/21/1 pts (=2 lines 25). Results: there were 1 CRs (4.3%), 10 PRs (43.5%), 6 SD (26.1%), and 6 PD (26.1%), for an overall response rate of 48% (exact 95% CI 27–69%). Median progression free survival was 6 months (+). Grade 3 side effects: 6 hypertension , 1 leucopenia , 2 neutropenia , 2 transaminitis (both with liver metastases). No patient was withdrawn from the study due to side effects, and hypertension was manageable with adequate therapy. Data on median circulating endothelial cells (CECs) will be available. Conclusions: Metronomic chemotherapy with capecitabine and cyclophosphamide in combination with bevacizumab has clinical activity and low toxicity in advanced breast cancer. No significant financial relationships to disclose.
Impact of cyclooxygenase-2 expression on the survival of glioblastoma multiforme
Authors: Choi Y. , Kim D. , Lee H. , Hur W. , Kim K. , Song Y. , Choi S. 
Published: March 2020

12505 Background: Expression of cyclooxygenase-2 (COX-2) protein in glioma patients increased proportionally to the pathologic grade. The extent of COX-2 expression is reported to have an inverse relation to survival rate in glioblastoma multiforme (GBM) patients, but the degree of COX-2 expression in the GBM specimens is variable from study to study. In order to evaluate the degree of COX-2 expression and its effect on survival in GBM patients, we conducted this study. Methods: Between 1997 and 2006, thirty consecutive patients of GBM who were treated with surgery and postoperative radiotherapy (range : 44 ∼ 65.1 Gy, median : 61.2 Gy) were included after exclusion of 3 patients who discontinued radiotherapy before 40 Gy due to mentality deterioration. Expression of COX-2 protein on surgical specimen was examined by immunohistochemistry. Survival analysis and verification were performed in respect to sex, age, resection extent, radiotherapy dose, and degree of COX-2 expression with Kaplan-Meier method and log rank test. Results: The median length of follow up was 13.25 months (6 ∼ 83 months). COX-2 was stained in all patients and COX-2 positives over 75% of tumor cells were found in 24 patients: positive in less than 25% of tumor cells, N = 3 (10.0%); 25 to 50%, 1 (3.3%); 50 to 75%, 2 (6.7%); 75 to 100%, 24 (80.0%). Median survival and 2-year survival rate were 13.5 months and 17.5%, respectively. The survival rate was influenced significantly by the degree of resection (tumor removal by 50% or more) and radiotherapy dose (60 Gy or greater) (p < 0.05). Median survivals of patients with COX- 2 positive in either more than 75% of tumor cells or at most 75% of tumor cells were 13.0 and 15.5 months, respectively (p>0.05), and the 2- year survivals of them were 13.3 and 33.3%, respectively (p>0.05). Conclusions: Eighty percent of the GBM patients were COX-2 positive in more than 75% of their tumor cells. The degree of COX-2 expression in the GBM patients had not a significant impact on survival, but the high positive rate of COX-2 in GBM could be a potential selective target for treatment. No significant financial relationships to disclose.
A retrospective safety and efficacy analysis of combination therapy using Gliadel wafers plus external beam radiation therapy with concurrent temozolomide in newly diagnosed glioblastoma multiforme patients
Authors: Pan E. , Mitchell S. B. , Tsai J. S. 
Published: March 2020

12510 Background: Safety and efficacy of malignant glioma treatment with carmustine-containing biodegradable implants (Gliadel® Wafers) followed by conventional radiotherapy (RT) and treatment with RT and concomitant temozolomide have both been well established. Multimodal therapy combining Gliadel® Wafers, RT, and temozolomide has recently demonstrated significant improvements in clinical outcomes of newly-diagnosed glioblastoma multiforme (GBM) patients. However, Gliadel® Wafer implantation in newly-diagnosed GBM patients is limited by the suspected risk of toxicities associated with multimodal therapy. Thus, the safety of multimodal therapy with Gliadel® Wafers, RT, and temozolomide needs to be determined. Methods: We conducted a retrospective analysis of medical records of 21 Florida Hospital Neuro- Oncology Center patients who were newly diagnosed with GBM from January 2003 to December 2005 and initially received multimodal therapy. All systemic and local toxicities were graded according to CTC AE v.3.0. Results were compared to historical data. Results: Our study population did not differ significantly from prior study populations with regard to patient demographics. 4 of 21 (19%) patients had grade 3 toxicities, which may have been related to multimodal therapy. None of the 21 patients had grade 4 toxicities. Median time to progression from initial surgery was 12.8 months (range 2–24 months). Median overall survival was 17 months (95% CI of 15–25 months). Conclusion: The addition of Gliadel® Wafers to concurrent RT and temozolomide did not result in a notable increase in grade 3 and 4 toxicities but did produce clinical outcomes comparable with those found in prior studies. The small sample size does not allow for definitive conclusions regarding efficacy. However, the addition of Gliadel® Wafers to concurrent RT and temozolomide appears to be safe in newly-diagnosed GBM patients. [Table: see text] No significant financial relationships to disclose.
Radiotherapy alone versus radiotherapy plus concomitant and post-radiotherapy temozolomide in newly diagnosed anaplastic astrocytoma
Authors: Elghazaly H. A. , Abdelkhalek S. A. 
Published: March 2020

12523 Background: Malignant gliomas (glioblastoma multiforme and anaplastic astrocytoma) occur more frequently than other types of primary central nervous system tumors, having a combined incidence of 5–8/100,000 population. Even with aggressive treatment using surgery, radiation, and chemotherapy, median reported survival is less than 1 year. Temozolomide, a new drug, has shown promise in treating malignant gliomas. in this study we evaluate the value of adding temozolomide concomitantly with radiotherapy and for 6 cycles after in newly diagnosed anaplastic astrocytoma over radiotherapy alone. Methods: patients with newly diagnosed , histologically confirmed anaplastic astrocytoma were randomly assigned to receive, group A radiation therapy alone ( localized irradiation 60 Gy, fractionated 2 Gy / fraction, 5 fractions / week for 6 weeks) orgroup B radiation therapy alone ( localized irradiation 60 Gy, fractionated 2 Gy / fraction, 5 fractions / week for 6 weeks) plus temozolomide 200 mg per square meter daily for 5 days orally from the 1st day of radiotherapy to be repeated every 28 days for a total of 8 cycles ( 2 during radiotherapy and 6 after). The primary end point were overall survival and safety. Results: A total of 70 patients were randomized , with 35 in each treatment group. Median age was 41 years in group A and 43 years in group B. Surgical resection was complete in 5 % patients,partial resection in 88 % and stereotactic biopsy in 7% patients. In the temozolomide group median survival was 16.7 months and it was only 11.3 months in the radiotherapy alone group. Temozolomide was also associated with a high response rate 62%(CR 8.5% and PR 54.2 %) versus 37% in radiotherapy alone group with minimal additinal toxicity in the temozolomide arm. Conclusions: This randomized phase II trial suggest that temozolomid is effective and add statistically significant survival benefit over radiotherapy alone in newly diagnosed anaplastic astrocytoma with minimal toxicity. No significant financial relationships to disclose.
Reirradiation for inoperable in-field recurrences of malignant gliomas
Authors: Schäfer U. 
Published: March 2020

12527 Background: To evaluate the effect of sequential radiochemotherapy in preirradiated malignant gliomas in a phase II study. Methods: Sixteen patients (median age 61 years) were treated according to a standardized treatment protocol consisting of sequential radiochemotherapy. The chemotherapy (temozolomide) was carried out over a duration of 5 consequential days (Mon-Fri) with a dose of 200 mg/m2/d. Chemotherapy courses were repeated in 4 week intervals (day 1, 29, 57, etc.) until clinical progression. Radiotherapy with 30 Gy over 3 weeks (5 x 2 Gy/week) was interposed between the first two chemotherapy courses (days 8–26). Results: 14/16 patients had no acute side effects. One patient suffered from acute thrombocytopenia (6000x106/l) and leukocytopenia (0,6x106/l), a further patient developed mental degradation (treatment stopped at 24 Gy). All patients have died due to disease progression. Median event-free survival (Kaplan/Meier method) amounts to 6 months. 7/16 patients survived longer than 10 months and one patient longer than 2 years. Late treatment sequelae have not been observed so far. Conclusions: The reported radiochemotherapy protocol is feasible for these otherwise difficult to treat patients without a remarkable increase in toxicity. In individual cases it can lead to stable disease over a period of 10 months and more. No significant financial relationships to disclose.
Venous thromboembolism in patients with brain tumors
Authors: Dhami M. S. , Goss D. , Dhami R. 
Published: March 2020

12528 Venous Thromboembolism (VTE) is common in patients undergoing treatment for brain tumors. American College of Chest Physicians (ACCP) 2004 consensus conference recommends routine use of intermittent pneumatic compression devices (IPC), unfractionated heparin (UH) or low molecular weight heparin (LMWH) for VTE prophylaxis in these patients. There, however, continues to be a reluctance on using pharmacologic VTE prophylaxis in these patients. The goal of our study was to determine the incidence of VTE in patients with brain tumors treated at a community hospital and the frequency of use of thromboprophylaxis in these patients. Both electronic and paper charts of all patients treated for brain tumors between 1997 and 2003 were reviewed. Follow up data was obtained by contacting physicians caring for these patients. Forty two patients were identified (Anaplastic astrocytoma 10; Glioblastoma multiforme 16; Meningioma 15; oligodendroglioma 1). Twelve patients were treated with various adjuvant chemotherapy regimens. Only 16 patients (38%) received any form of VTE prophylaxis. UH (12) or LMWH (2) were used with or without IPCs or graduated compression stockings. There were eight episodes of symptomatic VTE among 42 patients (19%). These include 6 episodes of deep vein thrombosis (DVT) and two cases of superficial vein thrombosis. Three patients with DVT also had symptomatic pulmonary embolus (PE). All episodes VTE were seen in patients with malignant gliomas yielding a 29% incidence of VTE in patients with malignant gliomas. None of the 15 patients with meningioma had symptomatic VTE. All but one episode of VTE were associated with administration of systemic chemotherapy. Half of these episodes occured more than six weeks after surgical debulking. We conclude that incidence of VTE with malignant brain tumors is high (29%) and the administration of chemotherpy increases this risk. There continues to be underutilization of VTE prophylaxis in these patients at very high risk of VTE. Efforts should be directed at improving the understanding of type and duration of appropiate VTE prophylaxis in patients with brain tumors. No significant financial relationships to disclose.
Predictive chemotherapy according to O6-methylguanine-DNA methyltransferase protein expression for treatment of malignant gliomas
Authors: Chen Z. , Zhang J. , Wu Q. 
Published: March 2020

12530 Background: To evaluate the response to predictable chemotherapy according to O6-methylguanine-DNA methyltransferase (MGMT) expression pattern and toxicity in patients with malignant gliomas. Methods: Twenty-eight patients with histologically confirmed malignant gliomas were enrolled in this study. The glioma tissues were examined for MGMT protein expression by immunohistochemistry. The chemotherapeutic regimen wasn’t consisted of nitrosourea or temozolomide in patients with MGMT positive expression, while no limitation using nitrosourea or temozolomide in patients with MGMT negative expression. The patients who received 2 or more than 2 cycles of chemotherapy were evaluated for response to therapy according WHO standard, and toxicity according National Cancer Institute (NCI) standard. Results: Twenty-four patients were used one regimen while 4 patients received two regimens chemotherapy, and thus overall 32 cases were evaluated for response to chemotherapy. The complete response (CR) was observed in 5 cases (16%),partial response (PR) in 6 cases (19%), stable disease (SD) was seen in 12 cases (38%), and 9 cases (28%) developed progressive disease (PD). Objective response rate (CR + PR) was 35%, and response plus stable disease rate (CR+PR+SD) was 73%. Hematological toxicity was the principal limiting side-effect observed in this study. Seven patients (25%, 7/28) experienced grade 3 or 4 leucopenia and one (4%,1/28) grade 4 thrombocytopenia who received platelet transfusion. No hemorrhagic event due to thrombocytopenia occurred. Non- hematological toxicity mainly was nausea/vomiting and alopecia. Grade 3 nausea/vomiting occurred in 7% of patients (2/28) and grade 3 alopecia in 7% of patients (2/28). Conclusions: The predictive chemotherapy according to MGMT protein expression in patients with malignant gliomas could improve overall response rate with acceptable side-effect, as compared with conventional chemotherapeutic regimen, and thus worth for further investigation. No significant financial relationships to disclose.
Monitoring effects of imatinib (Ima) plus gemcitabine (Ge) chemotherapy (CT) on functional status of tumors (T) using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and magnetic resonance spectroscopy (MRS)
Authors: Wolf W. , Presant C. A. , Waluch V. , Kim H. 
Published: March 2020

13001 Background: The ability to monitor the effect of all interventions on the functional status of tumors is critical in allowing clinicians to optimize/individualize chemotherapy to a given patient (pt). This is especially true when such pts are treated with a combination of targeting agents and cytotoxic anticancer drugs. The present study tested the combination of Ima and Gem to determine T pharmacokinetics (PK) and pharmacodynamics (PD) using DCE-MRI and 19F-MRS. Methods: Pts with measurable and MRI-imagible refractory solid T possibly responsive to Ge were randomized to receive either: one course of Ima with PK/PD, followed by one course of Ge with PK/PD, followed by the combination ImaGe; or one course of Ge with PK/PD followed by one course of Ima with PK/PD, followed by ImaGe. Ge was given at 900 mg/m2 IV over 30 min. for PK/PD and at 10 mg/m2/min. for continued therapy. Ima was given at 400 mg daily for 5 d. with Ge given on day 3. Doses were adjusted for toxicity. T vascularity (V) was measured by the use of DCE-MRI (AACR 95:490,2004). The initial contrast accumulation rate (ICAR) and the delayed contrast accumulation rate (DCAR) were calculated as the slope of the influx and efflux curves. Ge T PK was measured by serial 19F-MRS for ∼ 1hr post Ge administration. Results: 4 pts are evaluable at present: 2 Ca pancreas, 1 Ca breast and 1 Ca ovary. Ge PK are still in analysis. DCE-MRI data indicated an increase in T ICAR 1 week after Ima of 18% and 180% in 2 pts, and a decrease of -14% and -21% in 2 pt. By 2 wk post Ima, ICAR had further decreased to -75% in the latter pt. T size evaluation by RECIST showed progression of Ca in the 2 pt with increased ICAR, and a PR and stable disease in the 2 pt with a decrease in ICAR. Additional correlations with DCAR and Ge T PK will be shown. Conclusions: Ima and Ge CT is associated with a heterogeneous response in DCE-MRI. Ima has an antiangiogenic effect in some pts. This effect may be correlated with T response to Ima plus Ge. Measuring PK and PD using DCE-MRI and MRS may be useful in understanding individual responses to Ima drug combinations. No significant financial relationships to disclose.
Semi-physiological pharmacokinetic-pharmacodynamic (PK/PD) models for troxacitabine-induced neutropenia and thrombocytopenia
Authors: Ng C. M. , Muralidhar B. , Takimoto C. H. , Lin C. , Patnaik A. 
Published: March 2020

13002 Background: Neutropenia and thrombocytopenia are the dose-limiting toxicities of troxacitabine in Phase 1 studies. The present study’s aim was to develop a novel semi-physiological PK/PD model that can simultaneously describe the time course of the absolute neutrophil and platelet count changes in cancer patients receiving troxacitabine. Methods: The mixed-effect modeling was performed using the Monte-Carlo Parametric Expectation Maximization algorithm implemented in SADAPT program. The analysis was based on PK/PD data from 31 subjects who received troxacitabine/cisplatin combination every 28 days at five different dose levels (4.8/50, 4.8/75, 6.4/50, 6.4/75, 8.0/75 mg/m2). The PD model consisted of 1) a troxicatabine-sensitive uncommitted progenitor cell compartment, which differentiates into committed neutrophil and platelet progenitor cells that are also sensitive to the troxacitabine, and 2) transit compartments for neutrophils and platelets that represent maturation stages in bone marrow. To capture the rebound phenomena and maintain the hemostasis, the model included a feedback mechanism for both neutrophils and platelets. The troxacitabine concentrationtion-time profiles affected the proliferation of sensitive progenitor cells through an inhibitory sigmoidal Emax model. A three-compartment linear pharmacokinetic model was developed to describe the troxaicibatine concentration-time profile. Results: The PD model described the time-course of troxacitabine- induced neutrophil and platelet cytopenias and accounted for the large observed inter-patient variability. The model predicted that neutrophil progenitor cells were more sensitive to troxacitabine therapy compared to platelet progenitor cells. Furthermore, the model suggested that the troxacitabine-induced neutropenia and thrombocytopenia are reversible and non-cumulative events. Conclusions: This novel model can describe both the intensity and duration of troxacitabine-induced thrombocytopenia and neutropenia rather than simply considering the nadir values. It may be valuable for selecting treatment regimens that minimize troxacitabine’s dose-limiting hematological toxicities. No significant financial relationships to disclose.