tbuckley/cabot-search huggingface dataset:
Phase II trial of preoperative combined modality therapy for esophageal carcinoma: Induction cisplatin-irinotecan followed by concurrent cisplatin-irinotecan and radiotherapy
Authors: W. P. Tew, B. Minsky, M. Bains, N. Rizk, V. Rusch, D. P. Kelsen, M. Shah, S. Kepler, M. Gonen, D. H. Ilson
Journal: Journal of Clinical Oncology (2005)

4017 Background: We reported in a phase I trial that weekly cisplatin (C), irinotecan (I) and concurrent radiotherapy (RT) can be administered with minimal toxicity and acceptable response rates in esophageal cancer (JCO 21:2926;2003). We initiated a phase II preoperative trial to further evaluate this regimen. Methods: Patients (pts) with locally advanced esophageal cancer underwent pretreatment staging with esophagram, EUS, PET and CT scans. One 6-wk cycle of induction therapy with weekly I (65mg/m2) and C (30mg/m2) was given (wks 1, 2, 4, 5) and post-induction PET/esophagram were performed. Pts without progression were given daily RT (180cGy fractions to 5040cGy) with concurrent weekly C and I (wks 8, 9, 11, 12). Post-chemoRT endoscopy and CT scan were performed. At wk 16, pts without progression had esophagectomy. Results: 41 pts were evaluable: 33 men, 8 women, median age 60 (21–74), median PS 90%, adenocarcinoma 76%, squamous cell carcinoma 24%, and stage: 7pts T2–3N0, 3pts T3Nx, 3pts T1–2N1, 28pts T3N1, 31pts N1 (76%). Toxicity (grade 3–4): esophagitis 5%, neutropenia 37% (febrile 5%), thrombocytopenia 12% and thrombosis 15%. All 41 pts completed induction chemotherapy; 12% pts (5/41) progressed after induction, 18% (6/33) progressed after chemoRT, 3 pts are still on therapy and 1 pt awaits surgery. The remaining pts (24/26) underwent esophagectomy (1pt refused, 1pt delayed due to protracted thrombocytopenia). All 24 pts had R0 resections. Pathologic complete response (pCR) rate was 25% (6/24 pts). At surgery, 67% (16/24) pts were downstaged (58% T downstage, 29% N1 to N0), 29% pts had no change and 1pt had an increased stage. At baseline, 27 pts (66%) had dysphagia. After induction chemo, 15 pts (56%) normalized, 4 (15%) improved, 6 (22%) had no change and 2 (7%) worsened swallowing function. Only 2 (5%) pts required a feeding tube. Conclusion: I+C+RT resulted in a promising pCR rate (25%), downstaged disease (67%), improved dysphagia after induction therapy (71%) and had relatively low toxicity with rare feeding tube placement. Analysis of response data from post-induction PET scans will be presented. Supported by a grant from Pfizer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer, Roche Aventis, Pfizer
Abstract 9967: Microvolt T-wave Alternans in Adults with the Chosen Forms of Congenital Heart Disease
Authors: Olga Trojnarska, Aleksandra Cieplucha, Agnieszka Bartczak, Stefan Grajek
Journal: Circulation (2012)

Introduction. Sudden cardiac death (SCD) in adults with congenital heart diseases (CHD) is usually caused by ventricular arrhythmia (VA). Among the noninvasive methods of risk stratification for SCD is microvolt T-wave alternans (MTWA), reflecting repolarization inhomogeneity. We sought to determine the incidence of MTWA among adults with chosen forms of CHD as well as its coincidence with VA and other findings presumably associated SCD. Methods and Results. The study group: 102P with CHD characterized by pathology within right ventricle or single ventricle physiology (transposition of the great arteries after atrial switch, univentricular heart, Ebstein’s anomaly, congenitally corrected transposition of the great arteries, Eisenmenger syndrome, double-outlet right ventricle, common arterial trunk, unoperated tetralogy of Fallot). Controls: 45 volunteers age and sex-matched. All subjects underwent spectral MTWA test, ambulatory ecg monitoring, cardiopulmonary test, BNP assessement. MTWA positive and indeterminate were labeled ‘abnormal’ and were present more often in the study group, compared to controls (39,2% vs 2,3%, p=0,00001). Among subjects with abnormal MTWA sustained ventricular tachycardia (sVT) was observed more often compared to MTWA(-): 19,4% vs 3,6%, p=0,026. The patients with abnormal MTWA had a lower blood saturation (p=0,047), more often were males (p=0,031), had higher NYHA class (p=0,04), worse cardiopulmonary parameters: %PeakVO2 (p=0,034), %HRmax (p=0,003). Factors associated with abnormal MTWA: sVT (OR=20,7 p=0,037), male gender (OR=15,9 p=0,001) in multivariate regression; in univariate analysis: male gender (OR=2,7, p=0,021), presence of VA (OR=2,6, p=0,049), NYHA &gt; I (OR=2,06, p=0,033), %HRmax, %PeakVO2, VE/VCO2 slope (OR=0,94, p=0,005; OR=0,97, p=0,042; OR=1,05, p=0,037). Conclusions. The abnormal MTWA occurs significantly more often in adults with the chosen forms of CHD than among healthy subjects. The probability of abnormal MTWA increases in patients with malignant VA, in males and among subjects with heart failure and cyanosis. MTWA might be of potential role in risk stratification for SCD.
UGT1As polymorphisms predict toxicity in colorectal cancer patients treated with different recommended doses of irinotecan oriented by UGT1A1*28 polymorphism based on previous phase I study
Authors: S. Hazama, H. Koudo, S. Yoshida, R. Shimizu, H. Ozasa, T. Yamamoto, A. Araki, S. Yoshino, N. Okayama, Y. Hinoda, M. Oka
Journal: Journal of Clinical Oncology (2007)

14511 Background: We have presented at 2006 ASCO annual meeting about a genetic UGT1A1 polymorphism oriented phase (P) I study of Irinotecan and 5’-DFUR for metastatic colorectal cancer (MCRC) to determine the maximum tolerated dose (MTD) and the recommend doses (RD) for each UGT1A1 *1/*1 and *1/*28 genotypes. The RD of biweekly Irinotecan administration was 150 mg/m 2 for patients (pts) with wild *1/*1 genotype and 70 mg/m 2 of Irinotecan for mutated *1/*28. Now we are carrying out a *28 oriented P II study based on this RD. Here we report the profiles of toxicities in the P II study of irinotecan and 5’-DFUR to analyze other kinds of UGT1As polymorphisms in relation to irinotecan toxicities. Patients &amp; Methods: Eligibility criteria were as follows; histologically proven CRC with unresectable metastatic lesions, PS 0–1, age&lt;76, adequate organ functions, and written informed consent. Twenty one pts with wild type genotype and 9 pts with mutated genotype were enrolled. Irinotecan was infused 150 mg/m 2 for pts with *1/*1 genotype and 70 mg/m 2 for *1/*28. Hematological and non-hematological toxicities were graded, and UGT1As polymorphisms (UGT1A1*6 and *7, UGT1A7*1*2*3*4, UGT1A9*22) were analyzed. Results: Grade (G)3 &amp; 4 toxicities were observed in 6 of 22 (27%) wild type pts and in 3 of 9 (33%) mutated pts, and in 9 of 31 (29%) all pts. There was no significant difference on the profiles of toxicities between the pts with wild genotype and mutated genotype, irrespective of the difference of the quantity of irinotecan. So, the RD was thought to be adequate. In pts with UGT1A1*6 allele, G3 &amp; 4 toxicities were observed 6/11 (55%), on the other hand 3/20 (15%) in pts without *6 allele (p=0.038). G3 &amp; 4 toxicities were also more frequent in pts with UGT1A7*3 alleles than pts without *3 allele (p&lt;0.10). Conclusions: The profiles of toxicities of pts with *1/*1 or *1/*28 genotypes were similar irrespective of the difference of the quantity of irinotecan. The result indicated that the RD of latest PI for each group was adequate, and this P II study is suitable to analyze other kinds of polymorphisms that have correlation to irinotecan toxicities. UGT1A1*6 and UGT1A7*3 allele will be a novel predictor for toxicity of irinotecan. No significant financial relationships to disclose.
In vitro analysis of two formulations of fluticasone/ salmeterol pMDI for delivered dose uniformity and aerodynamic particle size distribution
Authors: Geena Malhotra, Kiran Rote, Anita Sawant, Jaideep Gogtay
Journal: European Respiratory Journal (2014)

Aim:  To compare the  in vitro  characteristics of fluticasone/ salmeterol HFA pMDI with an actuator having a dose indicator (Test Product) to the Reference Product.   Methods:  Two critical tests that qualify the performance of the product are Delivered dose uniformity and Aerodynamic particle size distribution. Delivered dose uniformity ensures that the total amount of drug emitted from the drug device and hence available to the user is consistent. The sampling apparatus used for determining the amount of delivered dose is the Dosage unit sampling apparatus manufactured by Copley scientific. Aerodynamic particle size distribution (APSD) of an aerosol cloud defines where the particles in that cloud are likely to deposit following inhalation. The APSD was performed on the Test Product (Cipla Ltd, India) and the Reference Product (Seretide Evohaler, UK) using an Anderson cascade impactor manufactured by Copley scientific. The fine particle dose was also estimated (i.e., the amount of the drug which is deposited into the lower airways of the lung during inhalation).   Results:  The delivered dose uniformity was within the acceptance criteria of 75% to 125% of delivered dose and the fine particle dose by cascade impactor is within the 15% for the test product compared with the reference product.   Conclusion:  These data confirmed that there were no significant differences in these critical quality performance attributes between the test product (fluticasone/ salmeterol HFA pMDI with an actuator having a dose indicator) and the reference product. These data further suggest that the  in vivo  performance of the test and reference product will be comparable.
Treatment patterns and outcomes of patients with pT3N0 rectal cancer in a population-based setting
Authors: B. S. Johal, P. Phang, C. McGahan, J. Hay, C. Brown, H. Kennecke
Journal: Journal of Clinical Oncology (2007)

4039 Background: Adjuvant radiation (R) and chemotherapy (C) is generally recommended for patients (pts) with pT3N0 rectal cancer. Patterns of adjuvant therapy and outcomes among pts with pT3N0 rectal cancer referred to the British Columbia Cancer Agency (BCCA) were determined. Methods: The BCCA Colorectal Cancer Outcomes Unit database was used to identify referred pts with pT3N0 rectal carcinoma diagnosed between 2000–2004. During this period, “short course” R (25Gy/5, surgery within 10 days) was recommended for resectable cT3 tumors followed by 6 months of C. If not treated pre-operatively (pre-op), guidelines specified post-op “long course” (45Gy/25) R and C. Three treatment groups were identified: Surgery alone (S), S and R (SR), and S, R and C (SRC). Eligible pts had complete surgical resection with or without Total Mesorectal Excision (TME). Pts treated with “downstaging” pre-op long course R, with S and C only (13 pts) or with R2 resection were excluded. Locoregional Recurrence (LR) and Distant Recurrence (DR) rates determined. Reasons for non-treatment were determined by chart review. Results: 303 pts were identified, with median follow-up of 33.5 months. Significant differences in age, tumor height, grade, and R therapy existed between groups ( Table I ). TME status, R status and Radial Margin positivity were similar. LR rates were 15% (S), 2% (SR) and 1.4% (SRC). DR rates were 11.7% (S), 7.9% (SR) and 8.5% (SRC). Median Overall Survival (OS) and Disease Free Survival (DFS) was not reached. Conclusions: Treatment of pT3N0 rectal cancer was variable and significant heterogeneity existed between groups receiving S, SR and SRC. Nevertheless, LR rates were very low in pts receiving R and substantially higher in pts who did not. DR rates were similar across groups, irrespective of C history. Reasons for not receiving R or C were primarily patient related (medical/post- operative considerations, patient refusal). Potential physician related factors (non-referral) accounted for 28% of lack of C treatment in the SR group. [Table: see text] No significant financial relationships to disclose.
Pharmacokinetic and Pharmacodynamic Study of the Combination of Docetaxel and Topotecan in Patients With Solid Tumors
Authors: William C. Zamboni, Merrill J. Egorin, David A. Van Echo, Roger S. Day, Barry R. Meisenberg, Sandra E. Brooks, L. Austin Doyle, Noble N. Nemieboka, Jason M. Dobson, Nancy S. Tait, Katherine H. Tkaczuk
Journal: Journal of Clinical Oncology (2000)

The sequence in which chemotherapeutic agents are administered can alter their pharmacokinetics, therapeutic effect, and toxicity. We evaluated the pharmacokinetics and pharmacodynamics of docetaxel and topotecan when coadministered on two different sequences of administration.On cycle 1, docetaxel was administered as a 1-hour infusion at 60 mg/m(2) without filgrastim and at 60, 70, and 80 mg/m(2) with filgrastim on day 1, and topotecan was administered at 0.75 mg/m(2) as a 0.5-hour infusion on days 1 to 4. On cycle 2, topotecan was administered on days 1 to 4, and docetaxel was administered on day 4. Cycles were repeated every 21 days. Blood samples for high-performance liquid chromatography measurement of docetaxel (CL(DOC)) and topotecan (CL(TPT)) total clearance were obtained on day 1 of cycle 1 and day 4 of cycle 2. CL(DOC) and CL(TPT) were calculated using compartmental methods.Mean +/- SD CL(DOC) in cycles 1 and 2 were 75.9 +/- 79.6 L/h/m(2) and 29.2 +/- 17.3 L/h/m(2), respectively (P: <.046). Mean +/- SD CL(TPT) in cycles 1 and 2 were 8.5 +/- 4.4 L/h/m(2) and 9.3 +/- 3.4 L/h/m(2), respectively (P: >. 05). Mean +/- SD neutrophil nadir in cycles 1 and 2 were 4,857 +/- 6, 738/microL and 2,808 +/- 4,518/microL, respectively (P: =.02).Administration of topotecan on days 1 to 4 and docetaxel on day 4 resulted in an approximately 50% decrease in docetaxel clearance and was associated with increased neutropenia.
Direct visualization of circulating sarcoma cells by whole-blood fluorescence in situ hybridization.
Authors: A. Morozov, M. Leversha, M. Keohan, D. R. D'Adamo, G. K. Schwartz, P. A. Meyers, R. G. Maki, M. A. Moore
Journal: Journal of Clinical Oncology (2010)

10637 Background: Several sarcoma subtypes are characterized by well-defined genetic events such as chromosomal translocations or gene amplification. In translocation-associated sarcomas, the presence of the fusion transcript can be detected in peripheral blood by RT-PCR. However, sarcoma cells have never been directly visualized in peripheral blood due to the absence of specific immunocytochemical markers. Methods: We developed a novel method to examine large numbers of peripheral blood cells for the presence of sarcoma-associated genetic changes. Using an IRB-approved biospecimen collection protocol, peripheral blood was collected from 20 patients with translocation-associated sarcomas or well-differentiated/dedifferentiated liposarcomas (WD/DD LS), which are characterized by MDM2 amplification. In this exploratory phase, the analysis was limited to patients with high burden of disease, evidence of disease progression or recurrence. Immuno-FISH was performed using CD45 immunostaining to identify hematopoietic cells and the corresponding FISH probe, either a break-apart probe (SYT, DDIT3) or MDM2 probe to detect amplification. Results: MDM2-amplified cells were detected in a subset of WD/DD LS peripheral blood samples, while translocation-positive cells were detected in samples of synovial sarcoma (using the SYT breakapart probe) and myxoid/round cell liposarcoma (using the DDIT3 breakapart probe). Conclusions: To our knowledge this is the first report of direct visualization of sarcoma cells in peripheral blood using whole-blood FISH analysis. We are currently characterizing these cells morphologically and immunocytochemically. In addition, we are developing tools necessary to perform quantitative analysis of circulating tumor cell frequencies in peripheral blood samples, to begin to establish whether the levels of circulating tumor cells correlate with tumor burden and response to therapy. This method may be applicable to other tumors where defined genetic lesions exist that are amenable to FISH analysis. The goal is to use such genotype-based analysis to explore the phenotypic diversity of circulating tumor cells. No significant financial relationships to disclose.
Management of worry about recurrence in breast cancer survivors.
Authors: Dean Alden Shumway, Rebecca Leinberger, Kent A. Griffith, Brian Zikmund-Fisher, Sarah T. Hawley, Reshma Jagsi, Nancy K. Janz
Journal: Journal of Clinical Oncology (2013)

21 Background: Worry about recurrence is a significant concern for breast cancer survivors. We explored physicians‘ confidence and practices in identifying and managing worry. Methods: We surveyed a random sample of 1,500 surgeons and medical oncologists drawn from the AMA Masterfile in 2012. Physician responses to questions regarding their confidence were stratified by practice specialty and compared using the Wilcoxon rank-sum test. Correlates of use of each strategy for managing worry were modeled using multiple variable logistic regression. Results: 896 physicians (59.7%) responded: 498 surgeons and 398 medical oncologists, of whom 85.5% saw breast cancer patients. 62% reported initiating discussions regarding worry about recurrence. Overall, medical oncologists reported more confidence than surgeons in their ability to present risk information to patients, identify survivors with high levels of worry, and help patients manage their worry (p&lt;0.001). Of note, 40.2% of physicians reported low levels of confidence managing worries surrounding recurrence. Confidence presenting risk information was significantly associated with treatment volume, which was highest with &gt;50 cases/year. Surgeons who routinely followed breast cancer survivors for &gt;3 years reported higher confidence; no such correlation existed among medical oncologists, but &gt;90% of this group routinely followed patients for &gt;3 yrs. Female physicians were significantly more likely to report being able to identify survivors with high levels of worry. Practice in an academic setting demonstrated associations with increased confidence. Use of worry management strategies varied by specialty. Medical oncologists were more likely to prescribe medication, address concerns in detail themselves, or refer to a psychologist or social worker. Longer follow-up was associated with increased likelihood of physicians addressing concerns themselves. Conclusions: A sizeable minority of physicians lack confidence in their ability to identify and manage worry in cancer survivors. Medical oncologists and surgeons differ significantly in their approach to worry management, suggesting that greater attention toward this issue in training and continuing education may be warranted.
Final report of a phase II study of oral cyclophosphamide, thalidomide, and prednisone (CTP) for patients with relapsed or refractory multiple myeloma: A Hoosier Oncology Group Trial: HEM01–21
Authors: A. Suvannasankha, C. Fausel, B. E. Juliar, C. Yiannoutsos, L. L. Wood, G. G. Smith, L. D. Cripe, R. Abonour
Journal: Journal of Clinical Oncology (2005)

6591 Background: Well-tolerated, effective and simple regimens are warranted in multiple myeloma (MM). Both thalidomide and prolonged administration of low-dose chemotherapy inhibit angiogenesis, rather than direct cytotoxic effect observed with acute dosing schedule. Synergy observed with the combined use may decrease toxicity, while maintaining antimyeloma effect. Methods: The Hooseir Oncology Group conducted a phase II trial of oral regimen containing cyclophosphamide (50 mg BID for 21 days per 28-day course), thalidomide (200 mg/day) and prednisone (50 mg Q.O.D.); CTP, in patients with relapsed and refractory MM. Therapy was planned for a total of 12 courses. Primary endpoints were efficacy and tolerability of the regimen. With 5% α error and 85% power, for expected response rate ≥ 30%, 12 responders among total of 37 patients were needed to pursue the trial further. Results: We report the final analysis of this study. Between November 2001 and June 2003, 37 patients were enrolled, 16 of whom had prior HDSCT and 22 had high dose steroid. Patient age ranged 49 to 87 (median 65) years. Two did not receive the study drugs due to progression and patient preference. Median follow up time was (95% CI 15.18–21.52) 18.37 months. Response was observed in 22 patients (63%); 7 (22%) CR, 2 (6%) nCR, and 13 (41%) partial response. Seven (22%) had stable disease, 3 (9%) had progression. Median time to best response was 3.7 (95% CI 2.9–10.9) months. Median time to progression was 13.24 months (95%CI 9.40 to 20.99). Median overall survival was 20.4+ months. The median number of treatment cycles was 7 (1–12). Major adverse effects included neutropenia (5 grade III and 5 grade IV), 4 grade III neuropathy, and 2 grade III Conclusions: The CTP oral regimen yielded high and durable response rate with acceptable toxicity profile and should be further explored in a larger patient cohort. No significant financial relationships to disclose.
A randomized double-blind phase IIa dose-finding study of ZD6474 in Japanese patients with NSCLC
Authors: K. Nakagawa, K. Kiura, T. Shinkai, K. Eguchi, Y. Ohe, N. Yamamoto, M. Tsuboi, S. Yokota, M. Fukuoka, H. Jiang
Journal: Journal of Clinical Oncology (2006)

7067 Background: ZD6474 is a once-daily oral therapy that selectively inhibits key signaling pathways in cancer by targeting vascular endothelial growth factor receptor (VEGFR)-dependent tumor angiogenesis, and epidermal growth factor receptor (EGFR)- and RET-dependent cancer cell proliferation and survival. ZD6474 was evaluated as monotherapy in an ongoing randomized, double-blind, parallel-group, Phase IIa, dose-finding, multicenter study in Japan. Methods: Patients with locally advanced or metastatic (stage IIIB/IV) or recurrent non-small-cell lung cancer (NSCLC), after failure of one or two platinum-based chemotherapy regimens, were eligible for this study. Patients were randomized to receive ZD6474 100, 200 or 300 mg/day in a 1:1:1 ratio, with stratification according to sex, histology (adenocarcinoma vs other histology) and smoking status (smoker vs non-smoker). Tumor response was assessed every 4 weeks for the first 24 weeks of treatment and then every 8 weeks until progressive disease (PD) or withdrawal due to any reasons other than PD. The primary objective was the objective response rate, as evaluated by RECIST. Secondary objectives included disease control rate, tolerability and safety. Adverse events (AEs) were assessed using CTC version 3.0. Results: A total of 53 patients (34 males/19 females, median age 60 years [range 30–78], 35 adenocarcinomas and 33 smokers) with a WHO PS status of 0 (n = 20) or 1 (n = 33) were recruited from eight centers between December 2004 and September 2005. Among 53 patients, 6 partial responses (PR; 11%, 2 males/4 females, 6 adenocarcinomas, 2 smokers/4 non-smokers) have been confirmed and disease control (PR or stable disease≥ 8 weeks) has been observed in 27 patients (51%). The most common AEs were rash and diarrhea, and asymptomatic QTc prolongation was also observed. One patient died due to drug-related interstitial lung disease. Conclusions: In this ongoing trial, ZD6474 has demonstrated antitumor activity as monotherapy in patients with refractory NSCLC, with 11% experiencing a PR and 51% having disease control. The tolerability profile of ZD6474 was consistent with that seen previously. [Table: see text]