tbuckley/cabot-search huggingface dataset:
A phase I evaluation of intravenous TM601 in recurrent glioblastoma: Use of perfusion MRI to monitor antiangiogenic effects
Authors: N. S. Akella, L. B. Nabors, S. S. Rosenfeld, M. C. Chamberlain, M. M. Mrugala, D. B. Jacoby, A. M. O'Neill
Journal: Journal of Clinical Oncology (2009)

2041 Background: TM601, a synthetic chlorotoxin, is a peptide derived from scorpion venom. In vitro data demonstrate binding to vascular endothelial cells, and blockage of endothelial cell invasion. In vivo, intravenous infusion of TM601 decreases neovascularization. Based on this work and previous clinical trials demonstrating tumor-specific uptake of 131 I-TM601 in malignant glioma after IV delivery, a phase I trial was initiated with intravenous unlabeled TM-601. Methods: Six patients with recurrent glioblastoma have been enrolled. All patients received a test dose of 10 mCi 131 I-TM601 to demonstrate tumor-specific uptake prior to TM601 treatment at doses of 0.04 mg/kg IV weekly for 3 weeks in a 4 week cycle. Treatment continued until tumor progression. Patients were evaluated at week 4 of each cycle with conventional and dynamic susceptibility contrast MRI (DSC-MRI) to assess perfusion. Anatomic and perfusion MRI evaluations were performed at baseline, 1 day after the initiation of TM601 therapy, and 21 days after initiation of each treatment cycle. MRI data were post-processed to yield an arterial input function and parametric hemodynamic maps. Results: With respect to safety, there has been one intratumoral hemorrhage that was considered to be possibly related to therapy. Three other serious adverse events considered to be unrelated to therapy included disease progression on therapy, a hip fracture and renal calculi in a patient with a history of renal calculi. Two of six patients in the first dosing cohort have demonstrated a greater than 25% reduction in relative cerebral blood flow (rCBF) and/or relative cerebral blood volume (rCBV) compared to baseline. Both patients with improvement in perfusion MRI had extended response to intravenous TM601. Conclusions: Intravenous unlabeled TM601 at the initial dose schedule produces measurable changes in perfusion MRI parameters which correlate with clinical response. Perfusion MRI parameters appear to correlate with clinical response to TM601 and are consistent with angiogenic inhibition. [Table: see text]
A phase I/II study of PHY906 plus capecitabine (CAP) in patients (pts) with advanced pancreatic cancer (APC)
Authors: C. J. Hoimes, L. Lamb, S. Ruta, K. Elligers, M. Mezes, N. Grant, S. Liu, J. Lacy, Y. Cheng, M. W. Saif
Journal: Journal of Clinical Oncology (2008)

15538 Background: PHY906 is a formulation of traditional Chinese medicine botanicals: Scutellaria baicalensis Georgi, Glycyrrhiza uralensis Fisch., Ziziphus jujuba Mill., and Paeonia lactiflora Palla. Our preclinical studies have indicated that PHY906 has synergistic anti-tumor activity with CAP in PANC-1 cell lines (Saif MW. ASCO 2007) and is a potent inhibitor of NF-κB. Studies in other tumor types have shown that PHY906 may reduce chemotherapy-induced GI toxicities, especially diarrhea and does not alter pharmacokinetics of CAP. These data have prompted phase I/II evaluation of safety and tolerability of a dose intense wkly (7/7) schedule for CAP plus PHY906. Methods: During phase I study, pts with advanced solid tumors (ST) who failed standard therapy or for which no standard therapy exists, ECOG PS ≤ 2, and adequate organ function were enrolled. Pts received PHY906 800 mg BID (D1–4) with escalating doses of CAP (1,000 mg/m2 →1,250 mg/m2 → 1,500 mg/m2 → 1,750 mg/m2 BID on D1 -7) followed by 7 days rest, until MTD was reached. During phase II study, pts with gemcitabine-refractory APC will be enrolled. Toxicity was assessed per NCI CTCAE v3.0 and response per RECIST q 6 wks. Results: To date, 23 pts [18 M/5 F; median age of 64 yr; PS 0: 7; PS 1: 14; PS 2: 2] have received 100 cycles [median (range)- 5 (1–18)] with PHY906 in 4 CAP (7/7) escalation cohorts: 1,000 mg/m2 (n = 6), 1,250 mg/m2 (n = 3), 1,500 mg/m2 (n = 6), and 1750 mg/m2 (n = 8). Dose-limiting toxicity (DLT) was observed in 1 of 6 pts at 1,000 mg/m2 dose [grade 4 AST/ALT]. No DLTs were seen at higher doses. However, delayed toxicities were seen at 1,750 mg/m2. Therefore, additional 3 pts have been added at 1,500 mg/m2 before moving onto the phase II part. Delayed grade ≥ 3 toxicities included hand-foot syndrome (n=3), nausea (n=3), mucositis (n=1), diarrhea (n=2), and hyperglycemia (n=2). One pt with cholangiocarcinoma had PR at cycle 3 and 9 pts experienced SD lasting ≥ 6 weeks (7 pancreas; 2 colon). Conclusions: Combination of CAP and PHY906 has acceptable toxicity in pts with ST. Phase II study will assess efficacy and quality of life in gemcitabine-refractory APC pts. Correlative chemokine (IL-2, IL-4, IL-5, IL-10, TNF-α, IFN-γ) levels, as surrogates for NF- κB expression, will be quantified by Cytometric Bead Array to help elucidate PHY906 mode of action. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Phytoceutica Phytoceutica Phytoceutica
Detailed urethral dosimetry in the evaluation of prostate brachytherapy-related urinary morbidity
Authors: Z. Allen, G. Merrick, W. Butler, K. Wallner, B. Kurko, R. Anderson, B. Murray, R. Galbreath
Journal: Journal of Clinical Oncology (2005)

4712 Background: To evaluate the relationship between urinary morbidity following prostate brachytherapy and segmental urethral doses. Methods: From February 1998 through July 2002, 186 consecutive patients without a prior history of a transurethral resection underwent monotherapeutic brachytherapy (no supplemental XRT or androgen deprivation therapy) with urethral sparing techniques (average urethral dose 100–140% mPD) for clinical T1c-T2b (2002 AJCC) prostate cancer. The median follow-up was 45.5 months. Urinary morbidity was defined by time to I-PSS resolution, maximum increase in I-PSS, catheter dependency and the need for postimplant surgical intervention. An alpha blocker was initiated approximately 2 weeks prior to implantation and continued at least until the I-PSS returned to baseline. Evaluated parameters included overall urethral dose (average and maximum), doses to the base, mid-prostate, apex and urogenital diaphragm, patient age, clinical T-stage, preimplant I-PSS, ultrasound volume, isotope, D90 and V100/150/200. Results: Of the 186 patients, 176 (94.6%) had the urinary catheter permanently removed on the day of implantation with only 1 patient requiring a urinary catheter > 5 days. No patient developed a urethral stricture and only two patients (1.1%) required a postbrachytherapy TURP. For the entire cohort, I-PSS on average peaked 2 weeks following implantation with a mean time to I-PSS resolution of 14 weeks. For the entire cohort, only isotope predicted for I-PSS resolution, while neither overall average prostatic urethra nor segmental urethral dose predicted for I-PSS resolution. The maximum post-implant I-PSS increase was best predicted by preimplant I-PSS and the maximum apical urethral dose. Conclusions: Detailed urethral dosimetry did not substantially improve the ability to predict urinary morbidity. Neither the average dose to the prostatic urethra nor urethral doses stratified into base, mid-prostate, apex, and/or urogenital diaphragm segments predicted for I-PSS normalization. Radiation doses of 100–140% mPD are well tolerated by all segments of the prostatic urethra with resultant tumorcidal doses to foci of periurethral cancer. No significant financial relationships to disclose.
Safety of Recombinant Human Factor IX, Nonacog Alfa, for Usual Use In Pediatric Patients: Results From a Prospective Registry of European Hemophilia B Patients.
Authors: Pablo Rendo, Erik Berntorp, David M. Keeling, Michael Makris, Cedric R. Hermans, Ereline Pauline Mauser-Bunschosten, Roberto Musso, Annarita Tagliaferri, Carl Kollmer, James Baumann, Robert Charnigo
Journal: Blood (2010)
Outcome prediction in adult male germ cell tumor patients through expression profiling
Authors: J. Korkola, J. Houldsworth, D. R. Feldman, A. B. Olshen, L. Qin, S. Patil, V. E. Reuter, G. J. Bosl, R. S. Chaganti
Journal: Journal of Clinical Oncology (2008)

5084 Background: Germ cell tumors (GCTs) are the most common solid malignancy in young adult men. Although GCTs are highly curable, when patients do succumb to disease, they have the greatest average number of life years lost of any adult cancer. Currently, patients are risk-stratified using clinical markers defined by the International Germ Cell Cancer Consensus Group (IGCCCG). Identification of molecular markers could improve outcome prediction. Methods: Expression profiling was performed on 74 non-seminomatous tumors (NSGCT) from patients who had received cisplatin based chemotherapy (training set) and 34 similarly treated NSGCT patients (test set). A modified version of Prediction Analysis for Microarrays (PAM) was used to develop a classifier for the binary endpoint of 5 year overall survival (5yOS). We also developed a predictive score for overall survival (OS) based on a weighted sum of the top genes derived using the univariate Cox model. Results: PAM identified a set of 170 transcripts that predicted 5yOS in the training set with a cross-validated classification rate of 60%. In the test set, the predictive gene set correctly classified 90% of the specimens. The predicted good and bad outcome groups showed significant separation in a Kaplan-Meier analysis. For the OS endpoint, we developed a 10 gene model that had a cross-validated predictive accuracy (concordance index, CI) of 0.66. Application of this model to the test set resulted in a CI of 0.83. Dichotomization of the samples based on the median score resulted in significant separation of the patients based on outcome in a Kaplan-Meier analysis. For both endpoints, the gene-based predictor was an independent prognostic factor in a multivariate model that included IGCCCG risk stratification (P<0.01 for both). Conclusions: We have developed and validated two gene-based models that predict outcome in GCT patients. These gene sets should have clinical utility for outcome prediction in GCT patients and should provide novel targets for therapeutic intervention. No significant financial relationships to disclose.
Comparison of tolerability and efficacy of concurrent chemoradiation (CRT) for anal squamous cell carcinoma (SCC) in HIV-positive (HIV+) and -negative (HIV-) patients (pts)
Authors: C. E. Souza, G. Castro, D. F. Saragiotto, W. Nadalin, D. R. Kiss, C. Nahas, S. A. Siqueira, P. M. Hoff
Journal: Journal of Clinical Oncology (2008)

4606 Background: It is believed that the prognosis of anal SCC is poor in HIV+ pts, and their appropriate treatment is uncertain. We compared the tolerability and efficacy of concurrent CRT as definitive therapy for anal SCC in HIV+ and HIV-/unknown pts in the HAART- era. Methods: Pts serially diagnosed and treated in a single institution from Apr/2000 to May/2007. Definitive CRT consisted of 45- 59.4Gy, divided in 5 fractions/week, given with concurrent mitomycin-C (MMC) 15mg/m2D1 IV and 5-fluoruracil (5FU) 1g/m2/d IV, continuous infusion, D1-D4 and D29-D32. Baseline hematologic, hepatic and renal functions were normal in all pts, and the same treatment was delivered irrespective of HIV-status. HIV+ pts were under antiretroviral therapy according to standard recommendations. Results: 78 pts were included in the analysis, median age 56.5y (23–85y), 63 female (81%). Stage: Tis (3 pts), I (4), II (26), IIIA (15), IIIB (20), IV (1). Nine pts were identified as HIV+. HIV+ pts were younger (39.4 vs. 59.2 y, p<0.0001) and predominantly male (8/9 pts). No difference in tumor stage or grade was detected in HIV+ pts. For all pts, the median dose of RT was 45Gy, given over 42d. No difference in terms of treatment duration or administered CRT intensity between HIV+ or HIV- /unknown pts was observed and treatment was well tolerated. Complete response (CR) was achieved in 45 pts (58%), partial response in 7 pts (9%), stable disease in 6 pts (8%) and disease progression in 3 pts (4%). No difference was seen in HIV+ pts in terms of CR rate (6/9 CR (67%), p=0.664). With a mean follow-up of 25mo, 14 deaths have occurred. The median overall survival (OS) was not reached (NR). The 2-y OS rate was 78%. No difference in OS was seen between HIV+ or HIV-/unknown pts (NR in both groups, p=0.248), and a 2-y OS rate of 100% was observed in HIV+ pts. We also observed both longer median PFS (NR vs. 11.5 mo, p=0.0009, HR 0.254, 95%CI 0.034–0.417) and median OS (NR vs. 12.9 mo, p=0.0007, HR 0.180, 95%CI 0.013–0.309) among patients that needed no colostomy. Conclusions: In this group of anal SCC pts no differences in terms of prognosis, treatment tolerance or efficacy could be identified based on HIV status, and the standard 5FU/MMC-based CRT could be delivered successfully. No significant financial relationships to disclose.
Australian prostate cancer survivors compliance to contemporary aerobic and resistance exercise oncology guidelines and associations with psychological distress, unmet supportive care needs and quality of life.
Authors: Daniel Abido Galvao, Robert Usher Newton, Robert Alexander Gardiner, Afaf Girgis, Stephen Lepore, Anna Stiller, Cathrine Mihalopolous, Stefano Stefano Occhipinti, Suzanne K Chambers
Journal: Journal of Clinical Oncology (2015)

e16089 Background: To determine prevalence of Australian prostate cancer survivors meeting contemporary exercise oncology guidelines and identify associations with distress, unmet supportive care needs and quality of life. Methods: A population-based cohort of 463 prostate cancer survivors who were 10.8 months post-curative therapy were assessed for compliance with current exercise guidelines for cancer survivors, motivational readiness for physical activity, psychological distress, unmet supportive care needs, and quality of life. Results: Only 57 men (12.3%) reported sufficient exercise levels (150 minutes of moderate intensity or 75 minutes of strenuous exercise per week and twice weekly resistance exercise), 186 (40.2%) were insufficiently active; and 220 (47.5%) were inactive. Among inactive men, 99 (45.0%) were in the contemplation or preparation stage of motivation readiness. Inactive men had higher global distress (p= .01) and BSI-Anxiety (p< .05) than those insufficiently active. Total supportive care needs and international prostate cancer symptom scores were higher in inactive than insufficiently and sufficiently active men (p< .05). Lack of physical activity contributed to poorer quality of life. Conclusions: Only a small proportion of Australian prostate cancer survivors met contemporary exercise oncology recommendations despite increasing recognition of exercise to improve patient outcomes. Strategies are urgently required to increase prostate cancer survivors’ participation in aerobic and resistance exercise training.
Predictive model of response to epoetin-alfa in anemic patients with solid tumors receiving chemotherapy: Results from a multicenter prospective study
Authors: J. M. Muñoz-Langa, O. Juan Vidal, S. Olmos, A. Albert, C. Molins, J. Campos, C. Bosch, V. Carañana, V. Alberola Candel, D. Almenar-Cubells
Journal: Journal of Clinical Oncology (2008)

20607 Background: The purpose of this prospective, multicenter study was to develop a model to predict hematopoietic response (HR) to epoetin alfa (EA) in anemic patients with solid tumors receiving chemotherapy (CT). Methods: Patients’ demographics, clinical and tumor characteristics, laboratory parameters and CT agents were collected just before the administration of each course of CT. Predictive factors for response (defined as an increase in Hb ≥ 2 g/dL or Hb level ≥ 12 g/dL during treatment) were tested in a univariate and multivariate analyses using logistic regression techniques. Finally a ROC analysis was undertaken to measure predictive accuracy. Results: A total of 409 pts (64% males) were included: a cohort of 205 pts received epoetin alfa 10,000 IU tiw and a second cohort of 204 pts received 40,000 IU qw. The response rate was 69.5%. Only four variables were independent predictive factors for HR: gender female (OR: 1.92; 95% CI: 1.05-3.49); percentage of underdose of EA respected to theoretical weight-based dosing [weekly dose administered/(450 IU qw*weigh)] (OR: 3.18; 95% CI: 1.2-8.42); Hb level at the begin of EA treatment (OR: 2.98; 95% CI: 2.2-4.03); change in Hb level after 3 weeks (OR: 2.96; 95% CI: 2.25-3.89). A statistical weight was assigned for each predictive factor on the basis of regression model beta coefficients to develop a predictive scoring system. The probability of HR was calculated over a range of total score (Table 1). A risk score of 5 was identified as being the optimal cut-off to maximize sensitivity (83.5%) and specificity (77.5%). Positive and negative predictive values were 89.2% and 67.5% respectively. The ROC analysis obtained an area under the ROC curve of 0.879 (95%CI: 0.845–0.912). Conclusion: This predictive model could be useful to identify patients at low probability of response to EPO in whom the increase of fixed dose of EPO adjusting to weight or the stop of EPO treatment could optimize the use of these molecules. Table 1. Score system and probability of response Predictive factor Score (0–9 points) Score Probability of response Gender: Female 1 0–2 < 15 % Percentage of underdose of EA: (weekly dose administered/450 IU*weight) < 90% 0 ≥ 90% 2 Hb at begin of treatment (g/dL): <8 0 3–4 30–50 % 8–8.9 1 9–9.9 2 10–10.9 3 Change Hb after 3 weeks (g/dL): < 0 0 5–7 60–80 % 0–0.5 0.5 0.6–1 1 1.1–1.5 1.5 >7 > 80 % 1.6–2 2 2.1–2.5 2.5 > 2.5 3 No significant financial relationships to disclose.
Randomized comparison of neoadjuvant docetaxel (D), epirubicin (E) and pegfilgrastim (P) (+ trastuzumab [T] in HER2+ patients [pts]) with and without capecitabine (C) for operable breast cancer (BC): Results of a planned safety analysis of ABCSG 24
Authors: G. G. Steger, R. Greil, H. Samonigg, R. Jakesz, R. Bartsch, B. Mlineritsch, E. Melbinger-Zeinitzer, C. Marth, W. Schippinger, M. F. Gnant
Journal: Journal of Clinical Oncology (2007)

11034 Background: ABCSG-24 is assessing the effect of adding C to DE and adding T to DE or DEC on pCR rate. Methods: Pts with operable BC (any T stage except T4d, N±, M0) scheduled for pre-operative chemotherapy were randomized to six 3- weekly cycles of D 75 mg/m 2 , d1 + E 75 mg/m 2 d1 + P 6 mg d2, ± C 1,000 mg/m 2 bid d1–14. Primary endpoint was pCR rate. After protocol amendment, HER2+ pts were also randomized to adjuvant ± neoadjuvant T. Results: From Nov 04 to Nov 06, 262 pts were enrolled, including 29 HER2+ pts. 145 are evaluable (DE: 74 pts, 400 cycles; DEC: 74 pts, 344 cycles). The table shows grade 3/4 adverse events (AEs) in &gt;2% of pts in either arm. Febrile neutropenia was absent. Serious AEs occurred in 22% vs 20% of pts in DE vs DEC, respectively. Fewer pts in the DE than the DEC arm required dose reduction (0.5% vs 6.6% of cycles), withdrew consent (4% vs 13%) or were withdrawn by the investigator (1% vs 17%). Reasons for withdrawal by investigator were: HFS, stomatitis, mucositis, diarrhea, vomiting, peripheral neuropathy, fatigue, asthenia, docetaxel hypersensitivity, and asymptomatic liver enzyme elevation. No serious or grade 3/4 cardiac toxicity has occurred with T. Conclusions: Despite infrequent grade 3/4 AEs in both arms, more pts discontinued DEC than DE, by either patient’s or investigator’s choice. Since May 06, no DEC pts have withdrawn consent, perhaps because of improved pt education and symptom management. This finding reinforces the need for close monitoring and prompt management of AEs. The addition of C to DE presents no safety concerns. Efficacy results are due in 2008. [Table: see text] [Table: see text]
The ASCO Annual Meeting and Excess Baggage
Authors: Mark Rosenthal, Michael C. Perry
Journal: Journal of Clinical Oncology (1999)

Article Tools Correspondence Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.9.3002 Journal of Clinical Oncology - published online before print September 21, 2016 The ASCO Annual Meeting and Excess Baggage Mark RosenthalxMark RosenthalSearch for articles by this author Michael C. PerryxMichael C. PerrySearch for articles by this author Show More Royal Melbourne Hospital, Parkville, Victoria, AustraliaEditor, ASCO Educational BookEditor, ASCO Program and Proceedings https://doi.org/10.1200/JCO.1999.17.9.3002 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyThe ASCO Annual Meeting and Excess Baggage091999In Reply: I appreciate Dr Rosenthal's taking time out to do these calculations. This is not the first time that the size of the ASCO Educational Book and Program and Proceedings has been brought to my attention. This chart represents the log phase of the Educational Book's growth since ASCO decided to change its structure and format and appointed an editor. We have not had limits on the manuscripts submitted by participants in the education sessions of ASCO until just now. These have just been implemented. If every speaker submits a manuscript of appropriate length, I anticipate the book will be the same size or slightly smaller. If, however, it must increase in size to accommodate all speakers, we will probably divide it into two volumes. While this will not decrease the total weight, it will make the volumes easier to carry.Regarding the size of the Program and Proceedings, that is the province of the ASCO Program Committee, which selects the abstracts for presentation and publication. I anticipate that the Committee may be more stringent in its selection, so the size of this volume may decrease also. We are considering publishing the 2000 edition in two volumes as well, one with publish-only abstracts and the other those that will be presented at the Annual Meeting.Meanwhile, think of all the aerobic exercise ASCO members experience carrying these volumes around!