tbuckley/cabot-search huggingface dataset:
Pharmacokinetics (PK) of intravenously (IV) administered epoetin alfa in pediatric patients receiving myelosuppressive chemotherapy
Authors: B. B. Freeman, L. C. Iacono, P. S. Hinds, B. I. Razzouk, C. F. Stewart
Journal: Journal of Clinical Oncology (2004)

8552 Background: The disposition of epoetin alfa (EPO, PROCRIT®) has not been well characterized in children. Therefore, we evaluated EPO PK in children with malignant solid tumors undergoing myelosuppressive chemotherapy. Methods: Children in this study were treated at a single center, but were enrolled in a multicenter double-blind, placebo controlled study of EPO. Children received IV EPO 600 IU/kg (max dose 40,000 IU) once weekly for 16 weeks. Serial PK studies were conducted after first EPO dose, and after ninth or tenth EPO dose. Plasma samples were obtained prior to EPO injection and at 0.25, 0.5, 1, 3, 6, 8, and 24 hours after EPO. Plasma EPO concentrations were analyzed using an ELISA assay, with a calibration curve ranging from 0.025 to 0.200 IU/mL. A two-compartment model was fit to the data using maximum likelihood estimation (ADAPT II). Results: 13 children were enrolled in the study, of whom 6 (median age 15.2 yrs; range 9.3–18.6 yrs) were randomized to receive EPO. Results from PK studies performed after the first EPO dose (n=6 patients) revealed a median (range) apparent AUC0–24 and clearance (CL) of 70.1 IU/mL*hr (17.29–108.0) and 0.25 L/hr/m2 (0.13–0.87), respectively. The median (range) apparent elimination rate constant (ke) after the first EPO dose was 0.12 h-1 (0.06–0.14). Subsequent PK analysis performed after the ninth or tenth EPO dose in 4 patients showed a median (range) apparent AUC0–24 and CL of 146.2 IU/mL*hr (116.0–172.9) and 0.11 L/hr/m2 (0.02–0.17), respectively. The median (range) apparent EPO ke in these 4 patients was 0.092 h−1 (0.0089–0.11). Conclusions: After multiple EPO doses, an increase in the median apparent EPO AUC0–24 was observed, whereas the median apparent EPO CL decreased by approximately half. The cause of these differences is currently being investigated. Future analyses will relate PK results with pharmacodynamic measures of hematopoeisis and quality of life. Study supported by Ortho Biotech Products, LP, and ALSAC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Oncology Ortho Biotech
Gene expression profiles of breast cancer obtained from core cut biopsies before neoadjuvant docetaxel, doxorubicin, and cyclophosphamide chemotherapy correlate with routine prognostic markers and could be used to identify predictive signatures
Authors: A. Rody, T. Karn, M. Munnes, G. von Minckwitz, S. Loibl, C. Solbach, U. Holtrich, M. Kaufmann
Journal: Journal of Clinical Oncology (2005)

646 Background: Neoadjuvant administration of chemotherapy before surgery provides a unique opportunity to directly monitor response to treatment in breast cancer and excactly assess response. Goal of our study was to examine the feasibility of performing gene expression profiling on pretherapeutic material in this setting. This approach can be used to correlate gene expression profiles with response to chemotherapy in order to identify predictive gene signatures to guide the selection of the individual therapy. Methods: Pretherapeutic core biopsies were obtained from 70 patients undergoing neoadjuvant TAC chemotherapy within the GEPARTRIO-trial. Samples were characterized according to standard pathology including ER, PR and HER2 IHC and amount of cancer cells. Only biopsies with more than 80% tumor cells were considered further. RNA was isolated and expression profiling performed using Affymetrix Hg U133 Arrays (22,500 genes). GeneData’s Expressionist software was used for bioinformatic analyses. Results: More than two thirds of the biopsies yielded sufficient amounts (> 5 μg) of RNA for expression profiling and high quality data were obtained for 50 samples. Unsupervised clustering broadly revealed a correlation with hormone receptor status. When ER, PR and HER2 as analyzed by immunohistochemistry were compared to the corresponding mRNA data from gene chips more than 90% concordance was observed. Furthermore, we used several described marker sets from microarray studies to classify patients in groups and evaluate their clinical data. However, no straight correlation with response was observed using these signatures, suggesting the necessity of class prediction methods to identify marker sets predictive for the type of therapy used. Conclusions: Our results demonstrate that reliable expression profiles can be achieved by using limited amounts of tissue obtained during neoadjuvant chemotherapy. Microarray data capture conventional prognostic markers but might contain additional informative gene sets correlated with treatment outcome. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Healthcare AG
Magnetic Resonance Imaging–Guided Transurethral Ultrasound Ablation of Prostate Tissue in Patients with Localized Prostate Cancer: A Prospective Phase 1 Clinical Trial
Authors: Joseph L. Chin, Michele Billia, James Relle, Matthias C. Roethke, Ionel V. Popeneciu, Timur H. Kuru, Gencay Hatiboglu, Maya B. Mueller-Wolf, Johann Motsch, Cesare Romagnoli, Zahra Kassam, Christopher C. Harle, Jason Hafron, Kiran R. Nandalur, Blaine A. Chronik, Mathieu Burtnyk, Heinz-Peter Schlemmer, Sascha Pahernik
Journal: European Urology (2016)
Final survival and safety results from a multicenter, open-label, phase IIIb trial of erlotinib in patients with advanced non-small cell lung cancer
Authors: V. O’Neill, J. Hainsworth, D. Spigel, J. D. Bloss
Journal: Journal of Clinical Oncology (2006)

7169 Background: Erlotinib is an orally available, reversible inhibitor of the EGFR tyrosine kinase with a proven survival advantage for patients with locally advanced or metastatic NSCLC who have failed one prior chemotherapy regimen. Preliminary data suggest that never smokers respond particularly well, as assessed by both response and survival. Method: This is a phase IIIb, multicenter, open-label trial of erlotinib in patients with advanced NSCLC who have progressed following standard chemotherapy treatment. The trial allowed patients access to erlotinib therapy prior to FDA approval; patients could remain on study up to 9 months following approval. The co-primary objectives were best ORR (as assessed by investigator) and OS associated with erlotinib therapy in this group, and in patient subsets defined by tobacco history. Secondary objectives include evaluating safety; characterization of OS and RR in sub-populations, including histology, sex, ethnicity; duration of time on treatment. Patients and Treatment: Between August and November 2004, 229 patients were enrolled and treated. Erlotinib was given at the standard dose of 150mg once daily. Demographics are as follows: M/F% 60/40; median age 68 (27–90); ECOG PS% 0/1/2/3 25/44/23/7; squamous histology 34%, adenocarcinoma 45%; &gt;1 prior regimen 47%; prior platinum 83%; never smoked 9%. Results: At the time of the final analysis (August 2005), 60% of subjects had died; data are therefore mature. Among the 229 treated subjects, the best ORR was 8.3% (CI: 5.2% - 12.4%). The ORR in never-smokers, previous smokers and current smokers was 28.6% (CI: 13.2% - 50.6%), 6.0% (CI: 3.0% - 10.4%) and 7.3% (CI: 2.0% - 19.0%), respectively. Median overall survival for all patients was 6.3 months (CI: 4.7 - 8.0). Median survival was 5.2 (CI: 4.2 - 7.3) and 6.3 months (CI: 3.6 - 9.2) in previous smokers and current smokers, respectively; and was not reached in never-smokers. Median duration of treatment was 10.6 weeks. One ILD-like event was reported (0.4%). Conclusions: No unexpected safety signals were seen. The observed ORR and survival data are consistent with the findings from the pivotal phase III randomized trial. [Table: see text]
Sunitinib in combination with paclitaxel and carboplatin in patients with advanced solid tumors: Updated phase I study results
Authors: E. I. Heath, G. R. Blumenschein, R. B. Cohen, P. M. LoRusso, N. LoConte, S. T. Kim, R. Chao, G. Wilding
Journal: Journal of Clinical Oncology (2009)

e14509 Background: Sunitinib (SU) is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, FLT3, and RET, approved for the treatment of advanced RCC and imatinib-resistant/intolerant GIST. Safety and antitumor activity of SU in combination with paclitaxel (P) and carboplatin (C) were evaluated. Methods: Successive pt cohorts with advanced solid tumors (STs) received oral SU at 25, 37.5, or 50 mg for 2 wks during 3-wk cycles (Schedule 2/1) or for continuous 3 wk cycles (CDD schedule) with P (175–200 mg/m 2 ) plus C (AUC=6 mg·min/mL) on day 1 of each of 4 cycles. Dose limiting toxicities (DLTs) and adverse events (AEs) were evaluated to determine the maximum tolerated dose (MTD). Response was evaluated for pts with measurable disease. Pts with clinical benefit continued on SU after 4 cycles under a continuation protocol. Results: Forty-three pts were enrolled (25 in Schedule 2/1 and 18 in CDD schedule). Median age was 58 yrs (range: 32–76), and 74% of pts had ECOG PS of 1. Tumor types included NSCLC (n=10), SCLC, esophageal, and pancreatic (n=4 of each), and other (n=21). In initial dose escalation cohorts, 4 DLTs were observed out of 23 pts (Heath et al. ASCO 2008). Based on overall tolerability, additional pts were enrolled on both schedules at SU 37.5 mg with P 175 mg/m 2 plus C. In these expanded cohorts, 2 more DLTs were observed in Schedule 2/1 (Gr 4 thrombocytopenia) out of 7 pts; dose escalation and further enrollment was stopped (Table). Gr 3/4 AEs (all cohorts) included neutropenia (63%), thrombocytopenia (47%), and leukopenia (35%). Of 35 pts evaluable for response, there were 4 confirmed partial responses and 3 additional patients with unconfirmed PRs. Conclusions: SU in combination with P/C may represent a clinically useful treatment option in pts with advanced STs. The determination of MTD based on observed DLTs/tolerability is ongoing. [Table: see text] [Table: see text]
Clinical translation of a high-performance neural prosthesis
Authors: Vikash Gilja, Chethan Pandarinath, Christine H Blabe, Paul Nuyujukian, John D Simeral, Anish A Sarma, Brittany L Sorice, János A Perge, Beata Jarosiewicz, Leigh R Hochberg, Krishna V Shenoy, Jaimie M Henderson
Journal: Nature Medicine (2015)
<i>Helicobacter pylori</i> infection as an independent prognostic factor for locally advanced gastric cancer with curative resection
Authors: S. Kang, Y. Hwang, H. Lee, S. Jeong, J. Choi, Y. Jo, S. Han, J. Kim, J. Han
Journal: Journal of Clinical Oncology (2009)

4562 Background: A few studies reported the association between helicobacter pylori (HP) infection and better overall survival (OS) in resected gastric cancer patients (pts). Methods: We investigated the HP infection status and its association with clinicopathologic characteristics in 210 locally advanced gastric cancer patients (stage IB: 18, II: 61, IIIA: 62, IIIB: 31, IV: 38) who underwent adjuvant chemotherapy (CTX) after curative resection (≥D2 dissection). HP infection status in hematoxlin and eosin stained peritumoral tissue was graded according to the updated Sydney System and categorized as HP(-) (normal or mild infection) and HP(+) (moderate or marked infection) (Am J Surg Pathol 20:1161, 1996). Twenty-two pts received 5-FU, doxorubicin (DOX) CTX (5- FU 500 mg/m2 weekly for 36 wks, DOX 40 mg/m2 q 3 weeks x 12) with or without OK432, while 188 pts underwent 5-FU, mitomycin-C (MMC), and polysaccharide-K (PSK) CTX (5-FU 500 mg/m2 weekly for 24 wks, MMC 8 mg/m2 q 6 wks x 4, PSK 3 g/day for 16 wks) (Br J Cancer 84:186, 2001, Hepatogastroenterol 54:290, 2007). Results: The median follow-up duration of survivors was 125 (107–155) months. HP (-) was significantly correlated with Bormann type IV, larger tumor size (&gt;5.5cm),and stage IIIB. In univariate analysis, patients with HP(-) (104 pts) demonstrated significantly poor 10-year OS compared with those with HP (+) (106 pts) (15.9% vs. 87.7%, p&lt;0.0001). HP(-) was associated with poor outcome in all stages except stage IB (p=0.075). In multivariate analysis, HP(-) was the most significant independent prognostic factor of poor OS (hazard ratio 9.646, 95% CI 5.407–17.206, p&lt;0.0001) followed by advanced stage (p=0.032), Bormann type IV (p=0.037) and old age (p=0.015). Conclusions: HP infection status seems to have strong prognostic significance in locally advanced gastric cancer. HP (-) pts may need intensified adjuvant treatment and careful follow-up. No significant financial relationships to disclose.
PD-L1 Is Upregulated by Simultaneous Amplification of the PD-L1 and JAK2 Genes in Non–Small Cell Lung Cancer
Authors: Seiichi Ikeda, Tatsuro Okamoto, Shinji Okano, Yuichiro Umemoto, Tetsuzo Tagawa, Yosuke Morodomi, Mikihiro Kohno, Shinichiro Shimamatsu, Hirokazu Kitahara, Yuzo Suzuki, Takatoshi Fujishita, Yoshihiko Maehara
Journal: Journal of Thoracic Oncology (2016)

ObjectivesThe programmed death ligand 1(PD-L1)/programmed cell death protein 1 (PD-1) pathway is one of the most important checkpoint pathways for mediating tumor-induced immune suppression through T-cell exhaustion. Recently, targeted therapies using monoclonal antibodies against components of this pathway have been shown to reduce tumor burden in patients with non–small cell lung cancer (NSCLC). However, the prognostic significance of PD-L1 expression is controversial and the precise mechanisms of PD-L1 gene activation in lung cancer have yet to be clarified.MethodsWe investigated copy number alterations (CNAs) in the PD-L1 gene by real-time PCR in 94 surgically resected lung cancer samples to find possible associations between PD-L1 CNA and lung cancer biology. Janus kinase 2 gene (JAK2) CNA and its influence on the PD-L1/PD-1 pathway were also assessed.ResultsFive samples were shown to have PD-L1 gene amplification, whereas 89 samples did not. The patients with PD-L1 amplification had worse prognoses than did those without PD-L1 amplification. Genetic amplification of the PD-L1 gene was correlated with JAK2 gene amplification. The lung cancer cell line HCC4006 was found to harbor both JAK2 and PD-L1 amplification. Flow cytometry analyses revealed the level of PD-L1 protein expression to be higher in HCC4006 cells than in other NSCLC cell lines. Expression of the PD-L1 protein was significantly reduced by the JAK2 inhibitor TG-101348 and the signal transducer and activator of transcription 3 (STAT-3) inhibitor BP-1-102, but not by the STAT1 inhibitor fludarabine.ConclusionsOur data suggest that expression of PD-L1 protein is upregulated by the simultaneous amplification of the PD-L1 and JAK2 genes through JAK-STAT signaling in NCSLC.
Opinions of the Turkish population on cancer and being informed for the diagnosis of cancer: An opinion survey
Authors: B. Yalcin, S. Yalcin, A. Buyukcelik, O. Sencan, M. Dogan, M. Turk, F. Ozdemir, A. Isikdogan, O. Er, H. Akbulut, F. Icli
Journal: Journal of Clinical Oncology (2007)

19680 Background: Opinions of the Turkish population on cancer, and their probable attitudes if one of their relative or themselves would have cancer diagnosis are investigated. Methods: The age, gender, profession, education levels of the subjects, their overall opinions on cancer are recorded by an opinion survey. Questions regarding if one of their first degree relatives had cancer, would they like the diagnosis being told to the patient and if they were to be the patient with cancer, would they prefer to be informed about the diagnosis are also asked. Results: 6566 subjects from various geographical regions of Turkey are participated in this survey. Participants’ median age were 33 years (range: 18–100), 53.3% were male. 57.7% of the participants would prefer to hide the cancer diagnosis from their first degree relatives. 54.8% of the participants had relatives with cancer and 69.9% of them said that the diagnosis had been told to the patient. The timing of the disclosure of the diagnosis were immediately in 71.5%, months after the diagnosis in 16.9% and in terminal stage in 9% of the patients. 62.8% of these patients are told to be died from cancer. When their overall opinion on cancer is asked, 76.5% were optimistic, 16.3% were pessimistic and did not believe the medicine, and 2.9% had both positive and negative opinions. Logistic regression analyses showed that 1) younger subjects; female subjects; subjects with lower education levels; subjects having a relative with cancer diagnosis which had not been revealed to the patient or revealed late in the course of the disease, or the patient had been died; subjects with pessimistic opinions about the treatment of the cancer were likely to hide the cancer diagnosis form their first degree relatives. 2) Elder subjects; subjects with lower education levels; subjects having a relative with cancer diagnosis which had been revealed to the patient; subjects having a relative with cancer diagnosis who died from cancer, subjects optimistic about cancer treatment; subjects preferring the diagnosis be hidden from patients were preferring not to be informed about the diagnosis if they were to have cancer. Conclusions: These results are comperable with reports form Eastern Europe and Asian countries. No significant financial relationships to disclose.
Screening and treatment of osteoporosis in breast cancer survivors treated with aromatase inhibitors: Gap between the national guidelines and real-world practice.
Authors: Sukriti Kamboj, Sandhya Sharma, Anuradha Sethi, Aref Agheli
Journal: Journal of Clinical Oncology (2014)

113 Background: Breast cancer survivors who are on adjuvant therapy with Aromatase Inhibitors (AIs) are known to have an increased risk of osteoporosis. AIs reduce estrogen levels and cause accelerated loss of bone density. Being at high risk for osteoporosis, these patients should be screened and followed up for bone mineral density (BMD) with dual energy X-ray absorptiometry (DEXA) scan as directed by national guidelines. The purpose of this study was to evaluate if this patient population is adequately screened and intervened appropriately. Methods: We conducted a two center, retrospective, clinical observational study at Guthrie cancer center at Sayre and Corning using Guthrie tumor registry. Patients with diagnosis of invasive breast cancer and on adjuvant therapy with AIs were included in this study. Patients with metastatic bone disease and those who were receiving palliative care were excluded. Results: During the study period, a total of 703 breast cancer patients were identified and 292 patients were on AIs. Baseline DXA scan for BMD was done in 54 % (158 out of 292) patients. Of these, 22% (n=35) had osteoporosis and 43% (n=68) had osteopenia. FRAX (Fracture risk assessment tool) score using WHO algorithm was calculated in patients with osteopenia. After calculating FRAX score, 28 of 68 patients were found to have ≥3% ten year probability (TYP) of a hip fracture or ≥20% TYP of a major osteoporosis-related fracture. These 28 patients with osteopenia and 35 patients (total n=64) with osteoporosis were required to be on treatment as per guideline recommendations. Only 23% (15 of 64) patients recieved treatment. Two year follow up on patients taking AI was done (n=292) and 46% (n= 137) patients had repeat BMD. Of the patients who had known osteoporosis and TYP of hip fracture ≥ 3% or a TYP of a major osteoporosis-related fracture ≥ 20%, only 54% (35 of 64) had follow up BMD. Conclusions: This study highlights the fact that osteoporosis is an under-detected and inadequately treated condition in breast cancer survivors who are on AIs. There is still a huge gap between guidelines and real world practice on prevention and treatment of osteoporosis this patient population.
Relapse of <i>TEL-AML1</i>–Positive Acute Lymphoblastic Leukemia in Childhood: A Matched-Pair Analysis
Authors: Karl Seeger, Arend V. Stackelberg, Tillmann Taube, Dirk Buchwald, Gabriele Körner, Meinolf Suttorp, Wolfgang Dörffel, Werner Tausch, Günter Henze
Journal: Journal of Clinical Oncology (2001)

PURPOSE: The aim of this study was to investigate whether, in relapsed childhood acute lymphoblastic leukemia (ALL), the frequent genetic feature of TEL-AML1 fusion resulting from the cryptic chromosomal translocation t(12;21)(p13;q22) is an independent risk factor. PATIENTS AND METHODS: A matched-pair analysis was performed within a homogeneous group of children with first relapse of BCR-ABL–negative B-cell precursor (BPC) ALL treated according to relapse trials ALL-Rezidiv (REZ) of the Berlin-Frankfurt-Münster Study Group. A total of 249 patients were eligible for this study: 53 (21%) were positive for TEL-AML1, and 196 (79%) were negative. Positive patients were matched for established most-significant prognostic determinants at relapse, time point, and site of relapse, as well as age and peripheral blast cell count at relapse. RESULTS: Fifty pairs matching the aforementioned criteria could be determined. The probabilities with SE of event-free survival and survival at 5 years for matched TEL-AML1 positives and negatives are 0.63 ± 0.10 versus 0.38 ± 0.10 (P = .09) and 0.82 ± 0.09 versus 0.42 ± 0.19 (P = .10), respectively. These results were confirmed by multivariate analysis, revealing an independent prognostic significance of time point and site of relapse (both P &lt; .001) but not of TEL-AML1 expression (P = .09). CONCLUSION: TEL-AML1 expression does not constitute an independent risk factor in relapsed childhood BCP-ALL after matching for relevant prognostic parameters. It undoubtedly characterizes genetically an ALL entity associated with established favorable prognostic parameters. High-risk therapeutic procedures such as allogeneic SCT should be considered restrictively.