bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Efficacy of Temozolomide in Patients With Recurrent Anaplastic Oligodendrogliomas After Standard Radiotherapy and Chemotherapy
Authors: Chinot Oliver-Louis , Honore Stephane , Dufour Henry , Barrie Maryline , Figarella-Branger Dominique , Muracciole Xavier , Braguer Diane , Martin Pierre-Marie , Grisoli François 
Published: February 2017

PURPOSE: Most primary oligodendrogliomas and mixed gliomas (oligoastrocytoma) respond to treatment with procarbazine, lomustine, and vincristine (PCV), with response rates of approximately 80%. However, limited data on second-line treatments are available in patients with recurrent tumors. A novel second-generation alkylating agent, temozolomide, has recently demonstrated efficacy and safety in patients with recurrent glioblastoma multiforme and anaplastic astrocytoma. This study describes the effects of temozolomide in patients with recurrent anaplastic oligodendroglioma (AO) and anaplastic mixed oligoastrocytoma (AOA). PATIENTS AND METHODS: Forty-eight patients with histologically confirmed AO or AOA who had received previous PCV chemotherapy were treated with temozolomide (150 to 200 mg/m2/d for 5 days per 28-day cycle). The primary end point was objective response. Secondary end points included progression-free survival (PFS), time to progression, overall survival (OS), safety, and tolerability. RESULTS: Eight patients (16.7%) experienced a complete response, 13 patients (27.1%) experienced a partial response (objective response rate, 43.8%), and 19 patients (39.6%) experienced stable disease. For the entire treatment group, median PFS was 6.7 months and median OS was 10 months. For objective responders, median PFS was 13.1 months and median OS was 16 months. For complete responders, PFS was more than 11. 8 months and OS was more than 26 months. Response correlated with improved survival. Temozolomide was safe and well tolerated. Twelve patients developed grade 1/2 thrombocytopenia and three patients developed grade 3/4 thrombocytopenia. CONCLUSION: Temozolomide is safe and effective in the treatment of recurrent AO and AOA.
Phase I Trial of Weekly Gemcitabine and Concurrent Radiotherapy in Patients With Inoperable Non–Small-Cell Lung Cancer
Authors: Trodella Lucio , Granone Pierluigi , Valente Salvatore , Turriziani Adriana , Macis Giuseppe , Corbo Giuseppe M. , Margaritora Stefano , Cesario Alfredo , D’Angelillo Rolando M. , Gualano Gina , Ramella Sara , Galetta Domenico , Cellini Numa 
Published: February 2017

PURPOSE: To report the evidence of a phase I trial planned to determine the maximum-tolerated dose (MTD) and related toxicity of weekly gemcitabine (GEM) and concurrent radiotherapy in patients with non–small-cell lung cancer (NSCLC). In addition, the response to treatment was evaluated and reported. PATIENTS AND METHODS: Thirty-six patients with histologically confirmed NSCLC deemed unresectable because of advanced stage were observed and treated according to a combined chemoradiation protocol with GEM as chemotherapeutic agent. GEM was given weekly for 5 consecutive weeks as a 30-minute intravenous infusion concurrent with radiotherapy (1.8 Gy/d; total dose, 50.4 Gy). The initial dose was 100 mg/m2. Pulmonary, esophageal, cardiac, hematologic, and skin toxicities were assessed. The dose of GEM was increased by 50 mg/m2 up to a dose of 250 mg/m2; an additional increase by 25 mg/m2 up to the MTD was planned and realized. Three patients were enrolled for each dose level. RESULTS: Dose-limiting toxicity was identified for the 375-mg/m2 level with two episodes of grade 2 esophagitis and two of grade 3 pulmonary actinic interstitial disease. The weekly dose of GEM 350 mg/m2 was well tolerated. CONCLUSION: A weekly GEM dose of 350 mg/m2 concurrent with radiotherapy was well tolerated. Promising results regarding response to treatment were observed and reported.
Clinical Factors Associated With Cancer-Related Fatigue in Patients Being Treated for Leukemia and Non-Hodgkin’s Lymphoma
Authors: Wang Xin Shelley , Giralt Sergio A. , Mendoza Tito R. , Engstrom Martha C. , Johnson Beth A. , Peterson Neomi , Broemeling Lyle D. , Cleeland Charles S. 
Published: February 2017

PURPOSE: To describe fatigue severity, fatigue interference, and associated factors in hematologic malignancies. PATIENTS AND METHODS: Patients being treated for leukemia and non-Hodgkin’s lymphoma (n = 228) completed the Brief Fatigue Inventory to rate fatigue severity and functional interference caused by fatigue. Data on patient demographics, Eastern Cooperative Oncology Group performance status, other physical symptoms, current treatments, and laboratory values were also collected. Descriptive statistics, bivariate correlation, and logistic regression were used for data analysis. RESULTS: Fifty percent of the sample reported severe fatigue, which was defined as a “fatigue worst” rating of 7 or greater. More patients with acute leukemia (61%) reported severe fatigue compared with those with chronic leukemia (47%) and non-Hodgkin’s lymphoma (46%). Increased fatigue severity significantly compromised patients’ general activity, work, enjoyment of life, mood, walking, and relationships with others. Fatigue severity was strongly associated with performance status, use of opioids, blood transfusions, gastrointestinal symptoms, and sleep disturbance items, as well as with low serum hemoglobin and albumin levels. Regression analysis indicated that nausea was the significant clinical predictor of severe fatigue (odds ratio, 13), and low serum albumin was the significant laboratory value predictor (odds ratio, 3.8). CONCLUSION: Disabling fatigue occurs with high frequency in hematologic malignancy, supporting a need to develop better methods of fatigue management. Better control of gastrointestinal and other symptoms may be of benefit. The mechanism and relationship between low albumin and severe fatigue needs to be investigated further, and longitudinal studies of the effects of treatment, host factors, and other symptoms are needed.
Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent and mantle cell lymphomas (MCL): Updated results from the StiL NHL1 study.
Authors: Rummel Mathias J. , Niederle Norbert , Maschmeyer Georg , Banat Andre G. , von Gruenhagen Ulrich , Losem Christoph , Kofahl-Krause Dorothea , Heil Gerhard , Welslau Manfred , Balser Christina , Kaiser Ulrich , Weidmann Eckhart , Duerk Heinz A. , Ballo Harald , Stauch Martina , Barth Juergen , Hinke Axel , Brugger Wolfram ,   Study Group Indolent Lymphomas (StiL)
Published: February 2017

3 Background: This multicenter, randomized, phase III study compared B-R and CHOP-R as first-line treatment in indolent lymphoma and MCL and was presented at ASH 2009 including a comprehensive safety analysis. Here we present an updated analysis with a cut-off date for 31 Oct 2011. Methods: 549 patients (pts) with indolent or MCL were randomized to receive B-R or CHOP-R for a max of 6 cycles. The primary endpoint was PFS. Results: 514 pts randomized pts were evaluable (261 B-R; 253 CHOP-R). Patient characteristics were well balanced between arms; median age was 64 years. At a median follow-up of 45 months, PFS was significantly prolonged with B-R compared with CHOP-R (HR 0.58, 95% CI 0.44–0.74; P<0.001). Median PFS was 69.5 versus 31.2 months, respectively. The PFS benefit with B-R was maintained in all histological subtypes except marginal zone lymphoma. The PFS benefit with B-R was independent of age; HR 0.52 (P=0.002) in pts ≤60 years (n=199), and HR 0.62 (P=0.002) in pts >60 years (n=315). In pts with normal LDH (62%), PFS was significantly prolonged with B-R compared with CHOP-R (P<0.001), while in the elevated LDH group (38%) PFS was numerically, but not significantly increased with B-R compared with CHOP-R (P=0.118). In patients with follicular lymphoma, FLIPI subgroups defined by 0–2 factors (favorable) and 3–5 factors (unfavorable) had a longer PFS with B-R than with CHOP-R (P=0.043 and P=0.068 for the favorable and unfavorable FLIPI subgroups, respectively). Seventy four salvage treatments had been initiated in the B-R group; compared with 116 in the CHOP-R group, of those in the CHOP-R group 52 pts received B-R as salvage regimen. Overall survival did not differ between the treatment arms, with 43 and 45 deaths in the B-R and CHOP-R arms, respectively. Twenty secondary malignancies were observed in the B-R group compared with 23 in the CHOP-R group, with 1 hematological malignancy in each group (1 MDS in B-R, 1 AML in CHOP-R). Conclusions: In patients with previously untreated indolent lymphoma, and elderly patients with MCL, B-R demonstrates a PFS benefit and improved tolerability compared with CHOP-R.
Prognostic impact of the 21-gene recurrence score (RS) on disease-free and overall survival of node-positive, ER-positive breast cancer patients (pts) treated with adjuvant chemotherapy: Results from NSABP B-28.
Authors: Mamounas Eleftherios P. , Tang Gong , Paik Soonmyung , Baehner Frederick L. , Liu Qing , Jeong Jong-Hyeon , Kim Seong-Rim , Butler Steven M , Jamshidian Farid , Cherbavaz Diana B. , Shak Steven , Julian Thomas B. , Lembersky Barry C. , Wickerham D. Lawrence , Costantino Joseph P. , Wolmark Norman 
Published: February 2017

1 Background: RS predicts outcome in node- and node+, ER+ pts treated with adjuvant endocrine therapy as well as benefit from adjuvant chemotherapy, with high RS receiving most of the benefit. We studied the prognostic impact of RS in node+, ER+ pts treated with adjuvant chemotherapy plus endocrine therapy as part of the NSABP B-28 trial. Methods: B-28 compared doxorubicin/cyclophosphamide (ACX4) with ACX4 followed by paclitaxel X4. Pts >50 yrs and those<50 yrs with ER+ and/or PR+ tumors also received 5 yrs of tamoxifen concurrently with chemotherapy. Between 8/95 and 5/98 3060 pts were accrued. The present study includes 1,065 pts ER+ by central tissue microarray IHC assay, tamoxifen treated, assessed by RS. Median follow-up time was 11.2 yrs. Results: Of the 1,065 pts, 386 (36%) had low RS<18; 364 (34%) intermediate RS,18-30; and 315 (30%) high RS≥31. In univariate analyses RS was a significant predictor of DFS, distant recurrence-free interval (DRFI) and OS (Table). In multivariate analyses, RS provided independent prognostic information for all three endpoints beyond clinical and pathologic factors, e.g., treatment, age, tumor size, tumor grade, number of + nodes and type of surgery (p<0.001). Conclusions: The 21-gene RS maintains significant prognostic impact in ER+, node+ pts who have received anthracycline- or anthracycline/taxane-based adjuvant chemotherapy. These findings emphasize the need to target pts with high residual risk for recurrence with additional therapies to overcome unfavorable biology, potential endocrine and/or chemotherapy resistance. Supported by: NCI, HHS, PHS, grants U10-CA-12027, -69651, -37377, -69974, and U24-CA-114732, and grants from Susan G. Komen for the Cure and Bristol-Myers Squibb Pharmaceutical Research Institute. [Table: see text]
Final overall survival (OS) and safety analyses of RIBBON-2, a randomized phase III trial of bevacizumab (BEV) versus placebo (PL) combined with second-line chemotherapy (CT) for HER2-negative BEV-naive metastatic breast cancer (MBC).
Authors: Brufsky Adam M. , Hurvitz Sara A. , Perez Edith A. , Yamamoto Hideharu , Valero Vicente , O'Neill Vincent , Rugo Hope S. 
Published: February 2017

100 Background: Combining BEV with CT significantly improved progression-free survival (primary endpoint) in the E2100, AVADO, and RIBBON-1 trials in the 1st-line setting and the RIBBON-2 trial in the 2nd-line setting. Primary efficacy and safety results from RIBBON-2 have been published; here we present final OS results. Methods: Eligible patients (pts) had MBC that had progressed on 1st-line CT without BEV. 2nd-line CT (taxane, gemcitabine, capecitabine, or vinorelbine) was chosen before 2:1 randomization to CT with either BEV (10 mg/kg q2w or 15 mg/kg q3w) or PL continued until progression. Stratification factors were 2nd-line CT, hormone receptor status, and time from MBC diagnosis to 1st progression. All pts could receive BEV at progression. The primary endpoint was PFS. Final analysis of OS, a secondary endpoint, in the intent-to-treat population was planned after 557 events and provided 80% power to detect a hazard ratio (HR) of 0.77 (median OS increased from 14.0 to 18.2 months) at α=0.04. Results: At the time of data cutoff (Oct. 31, 2011), 184 (82%) of 225 pts in the CT/PL arm and 376 (82%) of 459 pts in the CT/BEV arm had died. BEV was administered in subsequent treatment lines in 12% vs 6% of pts, respectively. There was no difference in OS between treatment arms: HR 1.013 (95% CI 0.845–1.215), log-rank p=0.8843. Median OS was 17.8 months with CT/PL vs 18.6 months with CT/BEV. The 1-year OS rates were 69% vs 71%, respectively. Subgroup analyses by CT cohort showed HRs ranging from 0.86 (95% CI 0.58–1.29) in the capecitabine cohort (n=144) to 1.44 (95% CI 0.82–2.53) in the vinorelbine cohort (n=76). HRs were close to 1 for the two largest CT cohorts (taxane and gemcitabine). Exploratory analysis in the subgroup of patients with triple-negative MBC showed a HR of 0.85 (95% CI 0.58–1.26). Updated safety results were similar to those previously reported from the primary analysis. There were fewer fatal adverse events in the CT/BEV arm (1.5%) than in the CT/PL arm (3.2%). Conclusions: Final OS results from RIBBON-2 reveal no difference between treatment arms. No new safety signals were observed.
Safety of everolimus in estrogen receptor–positive advanced breast cancer.
Authors: Perez Alejandra T. 
Published: February 2017

103 Background: Despite advances in treatment of estrogen receptor–positive (ER+) breast cancer (BC), resistance to endocrine therapy remains a frequent cause of disease recurrence. The mTOR pathway has been identified as a point of deregulation in patients resistant to standard therapy. Everolimus (EVE), an oral mTOR inhibitor, was evaluated as a potential antitumor therapy. Treatment-emergent adverse events (AEs) and their management are presented. Methods: BOLERO-2 (NCT00863655), a phase III trial, evaluated EVE in postmenopausal women with ER+ advanced BC refractory to letrozole or anastrozole. Patients with documented recurrence or progression were randomized 2:1 to receive daily oral EVE (10 mg) or matching placebo, in addition to exemestane (EXE; 25 mg/d), stratified by sensitivity to prior hormonal therapy and the presence of visceral metastasis. Results: At 12.5 months’ follow-up, PFS was 7.4 months in the EVE + EXE arm (n = 485) vs 3.2 months in the EXE-only arm (n = 239) (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.36-0.53; p < 1 × 10-l6). Notable AEs (all grades) in the EVE + EXE vs EXE-only treated patients included stomatitis (59% vs 11%), rash (39% vs 6%), pneumonitis (15% vs 0), and hyperglycemia (14% vs 2%). Grade 3-4 AEs of interest in the EVE + EXE vs EXE-only treated patients were stomatitis (8% vs <1%), anemia (7% vs <1%), hyperglycemia (5% vs <1%), pneumonitis (3% vs 0), and rash (1% vs 0). EVE doses could be reduced or interrupted for the management of AEs. Exploratory analyses of antitumor effects of EVE in patients who received time-averaged EVE doses <7.5 mg/d compared with ≥7.5 mg/d were consistent (HR, 0.4 [95% CI, 0.31-0.52] vs HR, 0.45 [95% CI, 0.37-0.56], respectively). Stomatitis was managed with topical corticosteroids and/or mouthwashes containing nonsteroidal anti-inflammatories or anesthetics. Noninfectious pneumonitis was managed by a combination of radiographic imaging, oral corticosteroids, and temporary cessation of treatment. Conclusions: Addition of EVE to EXE significantly prolonged PFS and was generally well tolerated. AEs were manageable with appropriate care. Knowledge of AE management strategies is essential to optimize EVE tolerability and patient outcomes.
Safety of everolimus for women over age 65 with advanced breast cancer (BC): 12.5-month follow-up of BOLERO-2.
Authors: Rugo Hope S. , Burris Howard A. , Gnant Michael , Baselga José , Piccart-Gebhart Martine J. , Noguchi Shinzaburo , Dakhil Shaker R. , Srimuninnimit Vichien , Puttawibul Puttisak , Csoszi Tibor , Heng Daniel Yick Chin , Bourgeois Hugues , Gonzalez-Martin Antonio , Osborne Karen , Mukhopadhyay Pabak , Taran Tanya , Campone Mario , Hortobagyi Gabriel N. , Sahmoud Tarek , Pritchard Kathleen I. 
Published: February 2017

104 Background: Postmenopausal women with estrogen-receptor–positive (ER+) BC who relapse/progress on a nonsteroidal aromatase inhibitor (NSAI) are usually treated with the steroidal AI exemestane (EXE), but there is no currently approved treatment for this indication. The BOLERO-2 trial showed that adding everolimus (EVE), an oral inhibitor of mammalian target of rapamycin (mTOR), to EXE significantly improved clinical benefit beyond that of EXE alone (Hortobagyi et al, SABCS 2011, Abstract S3-7). As many women with advanced BC are elderly, the tolerability profile of EVE + EXE in this population is of interest. Methods: BOLERO-2 is a phase III, randomized trial comparing EVE (10 mg once daily) vs placebo (PBO), both plus EXE (25 mg once daily), in postmenopausal women with advanced ER+ BC progressing or recurring after NSAIs. Safety data with a focus on elderly patients are reported at 12.5 months’ median follow-up. Results: Baseline disease characteristics, age, and prior cancer therapy were well balanced between treatment arms (N = 724). At 12.5 months’ median follow-up, the addition of EVE to EXE significantly improved progression-free survival in patients <65 (HR, 0.37; p < .05) or ≥65 years of age (HR, 0.56; p < .05). Adverse events (AEs) of special interest (all grades) occurring more frequently with EVE vs PBO (overall study population) included stomatitis (66.6% vs 11.3%), infection (50.4% vs 25.2%), rash (44.0% vs 8.4%), pneumonitis (18.7% vs 0.4%), and hyperglycemia (15.4% vs 2.5%). Elderly EVE-treated patients (≥65 years) had similar or marginally lower incidence of stomatitis (52.1%), rash (32.3%), pneumonitis (14.6%), and hyperglycemia (12.5%) compared with the overall population. Grade 3-4 AEs in patients ≥70 years of age (n = 161) reported only among patients receiving EVE (n = 118) included fatigue (10.2%), anemia (10.2%), hyperglycemia (8.5%), stomatitis (7.6%), dyspnea (6.8%), pneumonitis (5.1%), neutropenia (3.4%), and hypertension (3.4%). Conclusions: Adding EVE to EXE was well tolerated in the overall population and in elderly patients with advanced BC; grade 3-4 AEs were uncommon and manageable. Overall, AEs were consistent with the known safety profile of EVE.
Patient-reported outcomes (PRO) in patients with metastatic breast cancer (MBC) from the VIRGO observational cohort study (OCS).
Authors: Kaufman Peter Andrew , Mayer Musa , Dreyer Nancy A. , Yim Yeun Mi , Yu Elaine , Su Zhaohui , Mun Yong , Sloan Jeff A. , Cleeland Charles S. 
Published: February 2017

111 Background: Limited data exist on patient (pt) experience and work productivity (WP) in MBC. VIRGO is a prospective OCS following >1,200 pts with locally advanced or MBC receiving 1st-line hormonal therapy (HT) or chemotherapy (CT) in a real-world setting. We report baseline characteristics of 277 pts from the VIRGO PRO substudy and correlations between health-related quality of life (HRQoL), symptoms, activities of daily living, and WP. Methods: Symptom severity and interference (M.D. Anderson Symptom Inventory [MDASI]), functional status (Activity Level Scale [ALS] from the Rotterdam Symptom Checklist) and WP (Work Productivity and Activity Impairment Questionnaire) were assessed. Pts rated their HRQoL during the past week on a scale of 0–10. Results: See table. The five most severe symptoms at baseline were fatigue, decreased sexual interest, disturbed sleep, drowsiness, and emotional distress; these were reported with less severity in the HT cohort (24%-37% vs 42%-59%). Overall MDASI severity and interference correlated with WP measures in the CT (R=0.46 to 0.78) and HT cohorts (0.36 to 0.94). Mean of the 5 most severe symptoms also significantly correlated with WP indices (R=0.47 to 0.66). HRQoL correlated (p<0.05) with all WP measures (R=-0.46 to -0.56) in the CT cohort and with % impairment while working (R=-0.65) and % overall work impairment (R=-0.71) in the HT cohort. In univariate regression analysis, MDASI symptom interference score was the best predictor of reduced WP (R2=0.52 while working; R2=0.48 for non-work activities). Conclusions: MBC pts receiving CT and HT report significant work impairment. Results indicate moderate correlations between WP indices, HRQoL and symptom burden. [Table: see text]
Response of angiogenic factors to the treatment with melatonin in breast cancer cell lines.
Authors: Jardim Bruna Victorasso , Moschetta Marina Gobbe , Borin Thaiz Ferraz , Gelaleti Gabriela Bottaro , Leonel Camila , Ferreira Livia Carvalho , Lopes Juliana Ramos , Maschio Larissa Bazela , Goncalves Naiane do Nascimento , Zuccari Debora Aparecida Pires de Campos 
Published: February 2017

120 Background: Tumor growth and metastasis are the leading cause of death in breast cancer patients. The tumor growth requires neoangiogenesis, stimulated by vascular endothelial growth factor (VEGF) expressed under control of hypoxia-inducible factor-1α (HIF-1α). Melatonin, a natural hormone has been suggested as a new therapeutic agent to inhibit angiogenesis factors in several types of cancers. We evaluated the HIF-1α and VEGF expression in breast cancer cell line after hypoxia and treatment with melatonin. Methods: Breast cancer cell lines ER-positive (MCF-7) and ER-negative (MDA-MB-231) were cultured in DMEM at 37°C in 5% CO2. The cells were treated with CoCl2 to mimic hypoxia, and then treated with melatonin. Cell viability was measured by MTT assay with five melatonin concentrations (0.5mM, 1mM, 2mM, 5mM, 10mM). For the pharmacological concentration of melatonin (1mM) the protein and gene expression of HIF-1α and VEGF were detected by immunocytochemistry and real time PCR, respectively. Results: There was a significantly decrease in MCF-7 cells viability after treatment with all concentrations of melatonin and in MDA-MB-231 cells just with 1mM (p<0.05). The melatonin treatment did not alter the protein and gene expression of HIF-1α in MCF-7 cells (p>0.05), however, it significantly decreased the VEGF protein expression (p<0.05). In MDA-MB-231 cells there was significant decreased in the HIF-1α protein expression (p<0.05). Conclusions: Our results showed that 1mM of melatonin decreased the cell viability and HIF-1α protein expression in ER-negative cells, and VEGF protein expression in ER-positive cells. This study is the first that evaluated the expression of these angiogenic factors in breast cancer cells after treatment with melatonin that can be a potential therapeutic agent. Thus, we are performing in vivo study to confirm the potential effectiveness of melatonin in the control of angiogenesis in breast cancer.