tbuckley/cabot-search huggingface dataset:
Assessment and classification of pain in community dwelling elderly with cancer
Authors: N. Sarhill, R. Christie, M. Khalil, M. Moualla, K. Barakat
Journal: Journal of Clinical Oncology (2005)

8239 Purpose: To assess and classify pain in community dwelling elderly with cancer and evaluate the adequacy of prior analgesic therapy. Methods: Prospective assessment of 50 consecutive admissions of elderly cancer patients to the out-patient oncology Healthcare Center at St Vincent Charity Hospital, Cleveland, Ohio. Information collected included age, gender, and diagnosis. Result: 43 eligible were included (30 men and 13 women) with a median age of 73 years (range 65–99), most common diagnosis was lung cancer 19% (N=8). Pain was classify as intermittent pain (IP) only (non-breakthrough) in 51% (N=22), continuous accompanied by intermittent pain (breakthrough) in 32% (N=14), and continuous only in 17% (N=7). The etiology of pain was somatic (58%), visceral (19%), mixed (13%), or neuropathic (10%). Using our criteria, Non-breakthrough intermittent pain was the most common intermittent pain (61%). Incident pain accounted for 47%, non-incident 33%, mixed 13%, end of dose failure (EODF) 7%. Intensity of pain was moderate or severe in 79%. The analgesics consisted of around the clock (ATC) and as needed (PRN) only in 34%, PRN alone in 17%, and no pain medication in 49%. The most common used medication was oxycodone with acetaminophen in 32%. Pain associated with depression, anxiety and confusion in 42%. Conclusion: 1) pain in elderly with cancer is common, more underestimated and more undertreated compared to general cancer patients, 2) The etiology of pain is somatic in more than 1/2 of cases, 3) Non-breakthrough intermittent pain is the most common type of pain, 4) Incident pain in elderly is very common, 5) other component of pain such as depression and anxiety accounts in almost 1/2 of cases, 6) oxycodone compained with acetaminophen was the most common analgesic used. No significant financial relationships to disclose.
Abstract LB-106: Fusogenic-oligoarginine peptide-mediated silencing of the CIP2A oncogene suppresses oral cancer tumor growth in vivo
Authors: Angela Alexander-Bryant, Anca Dumitriu, Christopher Attaway, Hong Yu, Andrew Jakymiw
Journal: Cancer Research (2015)

Abstract Intracellular delivery and endosomal escape of functional small interfering RNAs (siRNAs) remain major barriers limiting the clinical translation of RNA interference (RNAi)-based therapeutics. Recently, we demonstrated that a endosome-disruptive peptide we synthesized termed, 599, could enhance the intracellular delivery and bioavailability of siRNAs designed to target the CIP2A oncoprotein (siCIP2A) into oral cancer cells and consequently inhibit oral cancer cell invasiveness and anchorage-independent growth in vitro. Thus, to further assess the therapeutic potential of the 599 peptide in mediating RNAi-based therapeutics for oral cancer and its prospective applicability in clinical settings, the objective of the current study was to determine whether intratumoral dosing of the 599+siCIP2A complex could induce silencing of CIP2A and consequently impair tumor growth using a xenograft oral cancer mouse model. Our results demonstrated that the 599 peptide was able to protect siRNAs from degradation by serum and ribonucleases in vitro, confirming the stability of the 599+siRNA complex and its potential for in vivo utility. Moreover, 599 peptide-mediated delivery of siCIP2A to tumor tissue induced CIP2A silencing without any associated toxicity, consequently resulting in reduction of the mitotic index and significant inhibition of tumor growth. Together, these data suggest that the 599 peptide carrier could be a clinically effective mediator of RNAi-based cancer therapeutics. Citation Format: Angela Alexander-Bryant, Anca Dumitriu, Christopher Attaway, Hong Yu, Andrew Jakymiw. Fusogenic-oligoarginine peptide-mediated silencing of the CIP2A oncogene suppresses oral cancer tumor growth in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-106. doi:10.1158/1538-7445.AM2015-LB-106
Phase II study of infusional 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for metastatic colorectal cancer
Authors: S. Kopetz, K. Y. Glover, C. Eng, R. A. Wolff, D. Z. Chang, R. B. Adinin, J. Morris, J. L. Abbruzzese, P. M. Hoff
Journal: Journal of Clinical Oncology (2007)

4089 Background: When compared to bolus 5-fluorouracil (F), leucovorin (L), and irinotecan (I) regimens such as IFL, the infusional F, L, I regimen (FOLFIRI) resulted in a improved toxicity profile with a response rate (RR) of 35% and median progression free survival (PFS) of 6.7 months. When combined with bevacizumab (B) as first-line treatment, IFL demonstrated improved activity with a RR of 45% and a median PFS of 10.6 months. Combining FOLFIRI and B may further improve the efficacy. Methods: We designed a single-arm, phase II trial of FOLFIRI+B with B (5mg/kg), I (180mg/m 2 ), bolus of F (400mg/m 2 ) and L (400mg/m 2 ) with a 46-hour infusion of F (2400mg/m 2 ) every 2 weeks. The primary endpoint was PFS. Chemotherapy naïve mCRC patients (pts) with a performance status of 0–2 received B alone on Day - 14, starting FOLFIRI+B on Day 1. Proteomic and radiographic correlative studies were completed and will be reported separately. Results: N=41 pts, median age 56 y/o (range 26–78), M:F = 16:25, 5 pts with prior adjuvant therapy, were enrolled from 1/2005 to 1/2007. A total of 502 cycles have been administered (median = 12). The median PFS is 12.6 months. Response rate by intention-to-treat analysis was 62% (24 pts), with 33% stable disease (13 pts). Responses occurred after a median of 4 months of therapy. Fifteen pts remain on treatment; 26 pts are off study: 7 for progressive disease, 2 withdrew consent, 7 for toxicity and 2 for surgery unrelated to cancer. Eight pts were removed from the study for metastasectomies. Grade 3 or 4 toxicities included 17 occurrences of grade = 3 neutropenia, including 1 grade 4 febrile neutropenia, 4 grade 4 pulmonary emboli, 2 grade 3 hand-foot syndrome, and 1 grade 3 diarrhea. One pt included in the analysis developed a possible microperforation, manifested by peritonitis, after B alone and never received FOLFIRI. Conclusion: FOLFIRI+B is well-tolerated and efficacious, with an impressive PFS that compares favorably to historical controls. This regimen is an excellent choice as a first-line treatment for mCRC. No significant financial relationships to disclose.
The study of sentinel lymph node detection in patients with carcinoma of uterine cervix
Authors: B. C. Acharya
Journal: Journal of Clinical Oncology (2008)

16586 Background: Cervical cancer is the seventh most common cancer, overall, and the third most common in women. Lymph node status is the most important independent prognostic factor in early stage cervical cancer of uterus. Intraoperative lymphatic mapping and sentinel lymph node (SLN) detection have been increasingly evaluated in the treatment of a variety of solid tumors, particularly breast cancer and cutaneous melanoma. We investigated to evaluate the feasibility of these procedures in patients undergoing radical hysterectomy with pelvic lymphadenectomy for treatment of early cervical cancer. Methods: Patients with histologically diagnosed FIGO stage IA to IIA carcinoma of uterine cervix were enrolled to this procedure who where scheduled to go radical abdominal hysterectomy and pelvic lymphadenectomy by injecting Patent Blue Dye in cervix. Results: 30 patients were enrolled to this study. A total of 60 SLNs (mean 2.5,) were detected in 24 patients with detection rate of 80%. Bilateral SLNs were detected in 70.1% of cases. SLNs were identified in obturator and external iliac areas in 50% and 31.7%, respectively; no SLNs were discovered in the common iliac region.7 patients (23.3%) had lymph node metastases; one of these had false negative SLN.The false negative rate and negative predictive value were 14.3% and 94.4%, respectively. Conclusions: SLN detection procedure with blue dye technique is a feasible procedure in cervical cancer of uterus. Patent blue dye is cheap, safe, and effective tracer to detect sentinel node in carcinoma of cervix. No significant financial relationships to disclose.
Genetic counseling and testing for <i>BRCA</i> mutations: A comparison of ethnically diverse families in a public hospital with Caucasian families in a university hospital
Authors: J. L. Ziegler, R. Lee, B. Crawford, J. Mak, N. Stewart, M. Beattie, J. Luce, L. Strachowski, L. Shaw, J. McLennan
Journal: Journal of Clinical Oncology (2005)

9667 Background: Genetic counseling and BRCA testing are largely unavailable to underserved women attending public hospitals because of cost and availability. A gift from Avon Foundation in 2001 enabled the UCSF CRP to provide genetic counseling and BRCA testing free of charge at San Francisco General Hospital (SFGH), starting in 2002. Women testing positive were able to choose risk-reducing procedures at no cost. Methods: The CRP began genetic counseling and BRCA testing in March 2002. We also administered a one-page multilingual family history questionnaire to women waiting for mammography as an additional recruiting tool. Results: The table shows our cumulative SFGH clinical experience for a 32-month period that compares the SFGH patients with the 8-year genetic counseling service at MZH. The family history questionnaire administered to over 4000 women yielded a 7% rate of very high-risk families, half of whom we could contact for referral through from their primary provider. Conclusions: Compared with the primarily Caucasian population at MZH, underserved women at SFGH have a similar proportion of BRCA mutations but are more likely to be BRCA 2 positive (p<0.001). Five patients carried 14 BRCA variants of unknown significance not previously encountered. Although health literacy, language barriers, and social adversity such as homelessness and addiction create barriers in underserved populations, this service was well accepted by providers and patients, and several patients have undertaken risk-reducing procedures. The family history questionnaire is an effective recruiting tool as 35% of our BRCA carriers were initially found by this questionnaire. Counseling challenges in this population include cancer histories in very large and dispersed families, better methods of genetic education for low literacy women, and accommodation to psychosocial hardships. No significant financial relationships to disclose.
Prevention of repeated benign endometrial pathology in postmenopausal women with breast cancer and tamoxifen-induced endometrial pathology: A randomized trial comparing anastrozole and tamoxifen
Authors: B. Gerber, W. Janni, A. Krause, H. Müller, T. Reimer, J. Makovitzky, G. Kundt, K. Friese
Journal: Journal of Clinical Oncology (2004)

584 Background: To study the effects of anastrozole versus tamoxifen in postmenopausal breast cancer patients with hormone-sensitive breast cancer and histologically proven, tamoxifen-induced benign endometrial pathology. Methods: A total of 171 tamoxifen-treated (20 mg/day >12 months) patients with abnormal vaginal bleeding (n=83) or thickened endometrium (demonstrated by transvaginal sonography, TVS), and subsequent histological clarification by hysteroscopy and dilatation and curettage (D&C;), were randomized to tamoxifen or anastrozole. Patients were monitored using TVS at 6-month intervals for up to 42 months. Results: There were no differences with respect to numbers of patients, tumor characteristics, endometrial thickness (tamoxifen: 12.9 ± 5.6 mm; anastrozole: 12.3 ± 5.8 mm) and histological findings before randomization. However, only 6 months after randomization, endometrial thickness in patients randomized to the tamoxifen arm differed significantly (6.7 ± 2.4 mm) from that of the anastrozole arm (3.3 ± 1.2 mm, p<0.0001). In 29 (33%) of the patients randomized to tamoxifen, a repeated hysteroscopy and D&C; was necessary, revealing 14 polyps, eight hyperplasias and seven atrophies. In the anastrozole arm there were four patients with vaginal bleeding, leading to repeated hysteroscopy and D&C; (p<0.0001). The results of the first and second histological assessments were consistent in 21 of 33 patients (63.6%; p=0.003). Although there were significantly lower numbers of endometrial changes and life-threatening side effects in anastrozole-treated patients, the cost–benefit analysis for endometrial changes was unfavourable for anastrozole-randomized patients (cost ratio = tamoxifen:anastrozole = 1:5). Conclusions: In breast cancer patients with tamoxifen-induced endometrial abnormalities, anastrozole represents an effective treatment for the prevention of repeated endometrial pathology. No significant financial relationships to disclose.
Low c-kit expression of cultured mast cells of mi/mi genotype may be involved in their defective responses to fibroblasts that express the ligand for c-kit
Authors: Y Ebi, Y Kanakura, T Jippo-Kanemoto, T Tsujimura, T Furitsu, H Ikeda, S Adachi, T Kasugai, S Nomura, Y Kanayama
Journal: Blood (1992)
CD4(+) cytotoxic T-cell clones specific for bcr-abl b3a2 fusion peptide augment colony formation by chronic myelogenous leukemia cells in a b3a2-specific and HLA-DR-restricted manner
Authors: Masaki Yasukawa, Hideki Ohminami, Shin Kaneko, Yoshihiro Yakushijin, Yasuharu Nishimura, Koiti Inokuchi, Tsuyoshi Miyakuni, Shinji Nakao, Kenji Kishi, Ichiro Kubonishi, Kazuo Dan, Shigeru Fujita
Journal: Blood (1998)
<i>ERG</i> rearrangements and association with clinical outcome in patients (pts) receiving abiraterone acetate (AA): Results from the COU-AA-302 study in chemotherapy (chemo)-naïve metastatic castration-resistant prostate cancer (mCRPC).
Authors: Gerhardt Attard, Johann Sebastian De Bono, Weimin Li, Arturo Molina, Thomas W. Griffin, Thian San Kheoh, Deborah Sokol Ricci, Kathy Zelinsky, Dana E. Rathkopf, Howard I. Scher, Charles J. Ryan
Journal: Journal of Clinical Oncology (2013)

5004 Background: ERG rearrangements result in androgen receptor-modulated up-regulation of ERG and may predict for AA response in mCRPC. Concordance has been shown between ERG status in archival samples and fresh CRPC biopsies (Attard et al., Cancer Res. 2009;69:2912). In this prospectively defined biomarker sub-study, the association between ERG subtypes and clinical outcome in chemo-naïve mCRPC pts receiving AA was evaluated. Methods: COU-AA-302 is a randomized double blind study of AA (1 g) + prednisone (P) (5 mg BID) vs placebo + P in chemo-naïve mCRPC. Fluorescence in situ hybridization (FISH) assays to evaluate ERG subtypes (Attard et al., Oncogene. 2008;27:253) were conducted on 524 archival prostate tissue samples (365 biopsies, 107 RPEs, 44 TURPs, 3 bone marrows, 5 lymph nodes) from 497 pts. Clinical outcome measures included radiographic progression-free survival (rPFS) (central [CEN] and investigator [INV] reviewed), time to PSA progression (TTPP), and PSA ≥ 50% decline. Cox regression was used to evaluate association with time to event endpoints and Cochran-Mantel-Haenszel for PSA response. Results: 337 of 497 pts with tumor samples had evaluable FISH results. An ERG rearrangement was present in 117 of 337 (35%) pts. 112 pts were class Edel, 50 were 2+Edel (interstitial deletion with duplication of fusion sequences) and 18 were ESplit. A trend for an association with greater improved rPFS (CEN) and TTPP in 2+ Edel pts treated with AA + P vs ERG non-rearranged was observed (22 months [m] vs 16 m [HR: 0.59, 95% CI: 0.30-1.16], p = 0.12, and 14 m vs 8 m [HR: 0.68; 95% CI: 0.41-1.15], p = 0.15, respectively). No differences in 2+ Edel vs ERG non-rearranged were observed in the P-alone arm. No association between any ERG sub-class and either rPFS [INV] or PSA ≥ 50% decline in either treatment arm was observed. Conclusions: This represents the largest study to date to molecularly characterize CRPC pts participating in a therapeutic phase 3 trial. These data suggest that chemo-naïve mCRPC pts with a 2+ Edel rearrangement may derive a slightly greater benefit from AA and P than other pts. Clinical trial information: NCT00887198.
A phase 1 trial of a novel organic arsenic S-dimethylarsino-glutathione (ZIO-101) in hematological malignancies
Authors: S. M. Kornblau, C. E. Jackson, A. Worthing, S. Faderl, M. Beran, L. Fayad, F. Ravandi-Kashani, G. Bothakur, R. Gale, S. Verstovsek
Journal: Journal of Clinical Oncology (2006)

16503 Background: Inorganic Arsenicals (IA, e.g. AS 2 O 3 ) kill many human leukemia cell lines and have efficacy in APL. Evaluation of efficacy against other types of leukemia is limited by the substantial toxicity of IA. Organic Arsenicals (OA) are less toxic than IA. ZIO-101 (S-dimethylarsino-glutathione) is an OA with activity against diverse cancers in in vitro tests and animals mediated through mitochondrial damage and apoptosis induction. ZIO-101 may induce apoptosis by different mechanisms than As 2 O 3 and can kill As 2 O 3 -resistant cancer cells. Compared to As 2 O 3, the LD 50 of ZIO-101 in mice is 50X higher and at equimolar extracellular arsenic concentrations ZIO-101 produces 15× higher intracellular arsenic concentration. These features make ZIO-101 attractive for evaluation in leukemia. Methods: A phase-1 study evaluating the safety and pharmacokinetic (PK) profile of ZIO-101 in subjects with advanced hematological malignancies is underway. 8 patients (PATS) with acute myelogenous leukemia (AML) (median 3 prior treatments) received ZIO-101 at doses of 78, 109 or 153 (n = 4, 3, 1) mg/m 2 /d IV for 5 d every mo. Results: Therapy with ZIO-101 has been safe and well-tolerated. Toxicities ≥ grade-2 included hyperglycemia (N = 3) and decreased albumin (N = 3) and Ca (N = 3) and 1 subject each had ≥ grade 2 elevations in LFT, or decreases in K, or PO4, febrile neutropenia and rash. Preexisting anemia and thrombocytopenia increased by 1 grade in 4 and 3 PATS each. Grade ≥3 neutropenia occurred in 2 PATS. No significant renal, liver or heart toxicity occurred, 1 patient with prior 1 0 AV block had transient prolongation of QT interval non-recurring on rechallenge. PK studies at 109 mg/m 2 /d showed a tmax = 1.5 h (SD ± 0.7 h), Cmax = 402 ng/mL (±33 ng/mL), t1/2 = 14.4 h (±2.9 h) and AUC0-∞ = 8.93 μg · min/mL (±1.82 μgzmdmin/mL). 4 PATS progressed after 1 cycle, 3 had stable disease and received a 2nd cycle: 1 progressed and 2 remain on study. 1 patient is too early to evaluate. Blood myeloblasts decreased (9 to 1.1 × 10e9/L at day 13) in 1 subject and completely resolved in 2 (pre-therapy: 100 and 336 × 10e9/L). Bone marrow myeloblasts were unchanged. Conclusions: Administration of ZIO-101 to PATS with advanced AML was safe and dose-escalation continues and a modest antileukemic effect has been observed. [Table: see text]
Mechanistic analysis of a novel, telomerase-specific oncolytic adenovirus targeting human gastric cancer stem cells.
Authors: S. Yano, S. Kagawa, H. Tazawa, F. Uno, Y. Hashimoto, Y. Urata, T. Fujiwara
Journal: Journal of Clinical Oncology (2010)

e13626 Background: Cancer stem cells (CSCs) are established firmly to play a key role in tumor formation, maintenance, and resistance to the conventional therapies. This resistance is reported to depend on quiescence of CSCs, and controlling cell cycle of CSCs is indispensable to eliminate CSCs. We constructed a telomerase-specific oncolytic adenovirus (OBP-301 [Telomelysin]), in which the hTERT promoter drives expression of E1 genes. OBP-301 causes selective replication and lysis of a variety of human cancer cells. A phase I study has been completed in the US to confirm the safety and pharmacokinetics of OBP-301 in patients with advanced solid tumors. Since telomerase activity is one of the stem-cell properties, OBP-301 may be capable of targeting human CSCs. Here, we examined the molecular mechanism of OBP-301-mediated cytotoxicity on CD133+ CSCs isolated from human gastric cancer cells. Methods: Radioresistant MKN45 and MKN7 human gastric cancer cells were obtained by sequential irradiation, and sorted for CD133+ and CD133− cells by flow cytometry. The CD133+ cells were confirmed for the characteristics of CSCs. We compared antitumor effects of chemotherapeutic agents, ionizing radiation, and OBP-301 on CD133+ and CD133-cells by XTT analysis. Western blotting was performed to determine the protein expression essential for the maintenance of stemness. Results: Although the fraction of CD133+ cells was 1-2% in untreated cells, radiation increased the CD133+ population to 18-20%. The CD133+ cells only have asymmetric division ability, sphere formation ability, and tumorigenicity. The cell viability assay demonstrated that CD133+ cells were less sensitive to the chemotherapeutic agents and ionizing radiation compared to CD133- cells, whereas OBP-301 could efficiently kill both CD133+ and CD133- cells. As CD133+ cells showed a higher telomerase activity, OBP-301 could replicate more efficiently in CD133+ cells. OBP-301 mediated cell cycle progression on quiescent CD133+ cells, while protein expression associated with the growth and stemness was reduced. Conclusions: Our data indicate that telomerase-specific OBP-301 might be a promising anticancer treatment against human gastric CSCs. No significant financial relationships to disclose.
Time to secondary resistance (TSR) after interruption of imatinib: Updated results of the prospective French Sarcoma Group randomized phase III trial on long-term survival
Authors: F. Duffaud, I. Ray-Coquard, B. Bui, A. Adenis, M. Rios, F. Bertucci, S. Chabaud, D. Perol, J. Blay, A. LeCesne
Journal: Journal of Clinical Oncology (2009)

10508 Background: We previously demonstrated that imatinib mesylate (IM, Gleevec/Glivec; Novartis Pharma) must not be interrupted after 1 and 3 years (yr) in responding patients (pts) and has to be given continuously until disease progression (PD) or intolerance. The impact of IM re-introduction at progression remains unknown regarding the impact of the interruption on the TSR. Methods: This prospective national multicenter BFR14 study was initiated in June 2002. After 1, 3, and 5 yrs of IM 400mg/day, pts free from progression were randomly offered to continue (C arm) or interrupt (I arm) IM. Pts allocated to the I arm could restart IM (same dose) in case of PD. Primary endpoint was PFS. Pts declining randomization proceed with IM. Results: As of December 2008, 415 pts were included in this trial. Fifty-eight, 50 and 12 (ongoing) non progressive pts at 1, 3 and 5 yrs respectively were randomized in the I and C arm. Pt characteristics were well balanced between the two arms. The median time to progression (TTP) were 7.3 months (m) (rate of relapse: 91% of pts) and 9.4 m (rate of relapse: 84%) in the I arms after 1 and 3 years of treatment. In contrast the median TTP were 31.4 m and not reached in the C arms after 1 and 3 yrs of IM treatment respectively. IM reintroduction in the I arm after a re-progression allowed again a tumor control in 93% (43/46) of pts. The median follow-up from randomization is 56 m and 25 m at 1 and 3 yrs respectively. TSR after randomization to IM (first progression in the C arm, 2 nd progression in the I arm) was not significantly different between the two arms (the 2-yrs TSR is similar in both arms 63% and 62% in the I and C arm respectively for the 1-yr randomization, 83.5% and 84.3% for the 3-yr randomization) but the rate of secondary resistance decrease over time in both arms: 40% or relapse in the 2 yrs following the 1 yr randomization vs less than 20% or relapse in the 2 yrs following the 3-yrs randomization. Conclusions: The majority of responding pts relapsed when IM was stopped after 1 and 3 yrs of treatment but response is reinduced in 93% of patients after IM reintroduction. TSR was not significantly affected by treatment interruption in this series of pts. [Table: see text]