tbuckley/cabot-search huggingface dataset:
Prognostic valude of Ki-67, TS, p53, bcl-2, EGFR, MLH1 and MSH2 in 107 consecutive colorectal cancer patients
Authors: C. Pinto, C. Ceccarelli, C. Funaioli, V. Mutri, F. L. Rojas Llimpe, F. Di Fabio, P. Paterini, M. L. Tardio, G. N. Martinelli, A. Martoni
Journal: Journal of Clinical Oncology (2005)

3694 Background: Bio-pathological studies of colorectal cancer (CRC) have provided informations into pathogenesis, but it is unclear how important these markers are in predicting prognosis and in clinical outcomes. The aim of this study was to evaluate the prognostic value of the expression of Ki-67, TS, p53, bcl-2, EGFR, MLH1 and MSH2 in specimens of CRC. Methods: The bio-markers were immunohistochemically determinated in the primary tumor of 107 consecutive pts who underwent surgery between June 2000 and August 2004. Pt characteristics were: males 69 (64.5%) and females 38 (35.5%); median age 68 (36–87); primary tumor site: right colon 40 (37.4%) and left colon 67 (62.6%); stage I 4 (3.7%), stage II 43 (40.2%), stage III 34 (31.8%) and stage IV 26 (24.3%); adjuvant chemotherapy with 5FU/AF regimen in 51 pts (47.7%); chemotherapy for advanced disease in 29 pts (27.1%). Median follow-up was 17 months (1–48). Results: No differences in marker expression were detected between right and left colon. The correlation between markers and disease stage, in univariate analysis, was as follows: Ki-67 expression decreased in higher stages: stage I-II mean 72.1%, III 63.3%, IV 65.2%, with statistical significant difference between stage I-II vs III (p=0.032); p53 expression decreased in higher stages: stage I-II mean 55,4% and IV mean 33.9% (p=0.037); negative MLH1 was prevalent in stage I-II vs III-IV (p=0.0125). No significant correlation was observed between expression of TS, EGFR, MSH2 and stage. No correlation was observed between molecular marker expression and relapse free survival (RFS) in stage II-III pts treated with adjuvant 5FU/AF chemotherapy. The evaluation of 77 stage II-III pts showed an association between bcl-2 expression and RFS % of cumulative survival (Kaplan-Meier test): bcl-2 negative = 75.5; bcl-2 intermediate = 81.4; bcl-2 positive = 100. No statistical association was found between p53, TS, EGFR, MLH1, MSH2 expression and RFS in this subgroup of pts, though there was a trend between p53 expression and higher % of RFS cumulative survival. Conclusions: This study suggests that Ki-67 is inversely correlated with disease stage and apoptotic markers may have a prognostic role in CRC. No significant financial relationships to disclose.
Phase II study for the suboptimally debulked advanced ovarian cancer: Intravenous platinum followed by interval debulking surgery and intravenous paclitaxel + intraperitoneal cisplatin (KCOG9812 study)
Authors: H. Tsubamoto, K. Ito, Y. Itani, K. Ito, T. Iijima, K. Hosokawa, S. Adachi
Journal: Journal of Clinical Oncology (2007)

5576 Background: Intraperitoneral administration (IP) of cisplatin is recommended by National Cancer Institute for the patients with optimally debulked epitherial ovarian cancer (EOC). However, the advantage is not determined for the suboptimally debulked EOC after the initial surgery. We conducted a phase II study of cisplatin IP after the interval debulking surgery (IDS) following 3 cycles of intravenous platinum. Methods: The initial planned sample size was 30. Eligible patients had previously untreated, histologically confirmed EOC or primary peritoneal carcinoma (PPC) of FIGO stage IIIB-IV with suboptimal (&gt; 1 cm) residual disease. Carboplatin AUC 4 iv d1 and cisplatin 50 mg/sqm iv d3 q21d for 3 cycles. After IDS, paclitaxel 175 mg/sqm iv d1 (or paclitaxel 60 mg/sqm iv d1,d8,d15) and cisplatin 75mg/m 2 IP q21d for 4 cycles. Primary endpoint was progression-free survival (PFS) and secondary endpoints were overall survival (OS) and toxicity. Results: 33 patients were enrolled since 1998 till 2005. The median age was 55 (range 19–77). ECOG PS 0/1/2 = 33%/36%/31%; stage IIIB/IIIC/IV = 6%/64%/30%; 91% serous papillary histology. Optimal interval debulking surgery was possible in 85%: none (61%), &lt; 1 cm (24%). Grade 3 or 4 (CTCAE ver.3) non-hematologic toxicity was seen in one patient of neurotoxicity. Grade 3 or 4 hematologic toxicities include: neutropenia (37%), infection (4%), thrombocytopenia (11%). 55% were completed the treatment schedule. The reasons for discontinuing were drug resistance (12%), subileus (4%), elevation of serum creatinine (12%), G3 neurotoxicity (4%), IP catheter block (12%) and infection (4%). Primary recurrent sites of total 20 patients before the second line chemotherapy or surgery were peritoneal cavity (30%), distant metastasis (45%), retroperitoneal lymph nodes (15%), and elevation of serum CA125 (10%). Median PFS was 24 months; median overall survival was 48 months; median follow-up was 36 months (range 15–100). Conclusions: This treatment including cisplatin IP after IDS for the patients with the initially suboptimally debulked EOC was feasible, and showed good prognosis with the small number of the intraperitoneal recurrence. [Table: see text]
Enhanced Efficacy and Confirmed Safety of a Two-Year Epicutaneous Immunotherapy (EPIT) Treatment of Peanut Allergy with Viaskin® Peanut: The Continuation of the Vipes Phase IIb Randomized Controlled Trial (RCT)
Authors: Hugh A. Sampson, Wence Agbotounou, Claude Thébault, Charles Ruban, Laurent Martin, Gordon L. Sussman, Terri F. Brown-Whitehorn, William H. Yang, Kari C. Nadeau, Amarjit Singh Cheema, Stephanie A. Leonard, Christine Sauvage, Amal H. Assa'ad, Frederic de Blay, J. Andrew Bird, Stephen A. Tilles, Franck Boralevi, Thierry Bourrier, Pierre-Henri Benhamou, Christophe Dupont
Journal: Journal of Allergy and Clinical Immunology (2016)
Safety and tolerability of oral halofuginone hydrobromide in refractory recurrent transitional cell carcinoma of the bladder
Authors: O. Nativ, A. Thorpe, M. Laufer, H. Matzkin, M. Salzberg, S. Yarkoni, B. Dezube, A. Harris
Journal: Journal of Clinical Oncology (2004)

4757 Background: Halofuginone hydrobromide (Tempostatin) is an orally bioavailable quinazolinone derivative that acts as a signal transduction inhibitor in stromal cells and susceptible tumor cells. In animal models of bladder cancer, halofuginone inhibits growth of primary tumor and metastases at exposures (AUC) of 4–8 ng*hr/ml by supressing angiogenesis, tumor cell proliferation, and invasion. Methods: A phase II dose-intensity study in refractory recurrent TCC with halofuginone administered orally at 0.5 mg BID for 6 months. Treatment is started immediately following TUR and continues until tumor recurrence or unacceptable tolerability. Patients are monitored for tumor recurrence by cystoscopy and cytology at 3-month intervals. Results: 11 patients (5 M, 6 F), median age 77 yrs (range 52–87), have been enrolled. Total treatment days is >1200. Two patients are relapse-free and continue taking study drug beyond 6 months. Adverse events possibly related to therapy: nausea and/or vomiting grade 1–2 (resolved spontaneously or with anti-emetics) (4 patients). One patient each reported headache grade 2, fatigue grade 1, and indigestion grade 3. One patient experienced transient anemia that resolved while continuing therapy. No other significant changes in laboratory parameters were observed. Pharmacokinetic samples were analyzed for 7 of the 11 patients. Mean plasma AUC on Day 1 was 2.4ng.h/ml (1.16–3.09 ng.h/ml) and on Day 15 10.26 ng.h/ml (4.4–15.8ng.h/ml). Mean Cmax on Day 1 was 0.47 ng/ml and on Day 15 was 2.087 ng/ml. Drug concentration in urine on Day 15 was 87.87–197.95 ng/ml (mean 139.8 ng/ml). Conclusions: Split-dose oral halofuginone 0.5 mg is well tolerated, concentrated in the urine, and achieves AUC values exceeding those that inhibit bladder cancer in animal models. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Collgard Biopharmaceuticals Collgard Biopharmaceuticals Collgard Biopharmaceuticals
Preliminary immune response (IR) results of a phase 2 study with idiotype (Id) immunotherapy after treatment with CVP and rituximab for follicular non-Hodgkin’s lymphoma (FL)
Authors: J. P. Leonard, K. Mason, T. Theriault, K. Milner, T. Sornasse, D. Ingolia, M. Mayo, D. W. Denney
Journal: Journal of Clinical Oncology (2006)

7529 Background: Idiotype (Id) is a collection of unique immunogenic epitopes present on the surface of malignant B cells. Keyhole limpet hemocyanin (KLH) is a carrier protein used to increase antigen immunogenicity. MyVax Personalized Immunotherapy consists of the patient- and tumor-specific Id protein, produced using molecular techniques, conjugated to KLH and administered in a series of subcutaneous immunizations with the adjuvant GM-CSF. Idiotype vaccines were first studied in combination with various chemotherapeutic agents as part of initial treatment for FL. Given the widespread usage of rituximab in treating FL, the nature of IRs in patients immunized with MyVax Personalized Immunotherapy following rituximab treatment are of interest. CD19 + B cell counts following treatment with rituximab were analyzed for correlation with patient-specific Id-KLH induced humoral IR data. Methods: In a Phase 2 study, MyVax Personalized Immunotherapy following rituximab is being evaluated for patients who failed to achieve at least a PR and maintain the response over a 6 month rest period after 8 cycles of CVP chemotherapy. Eligible patients received 4 weekly doses of rituximab followed by a 13 or 26 week rest period. Patients who achieved and maintained a PR or better then received 8 immunizations with MyVax Personalized Immunotherapy over 14 weeks. CD19 + B cells and humoral IRs against Id and KLH were monitored during and 2, 8, 20, 32, 44 and 56 weeks post-immunizations. Results: 87 pts received rituximab. 52 pts went on to immunization. Median CD19 counts for all arms of the study were lower post-rituximab treatment (pre-treatment median = 76 cells/ul (N = 57) vs. post-treatment = 13 cells/ul (N = 51 evaluable); p &lt; 0.0001). Positive results are defined as a titer &gt;0.1 mcg/ml. 49/52 (94%) evaluable pts were able to mount anti-KLH humoral IRs post rituximab. The magnitude of the anti-KLH response was generally greater in pts with higher B cell counts when beginning immunizations. Anti-Id IRs were also observed. Conclusions: Humoral IRs to KLH occur in pts receiving MyVax Personalized Immunotherapy and correlate with regeneration of B cells post-rituximab but appear less robust than in rituximab-naïve pts. [Table: see text]
Abstract P276: Aerobic Endurance and Leg Strength are Predictive of Gait Velocity among Community-Dwelling Stroke Survivors
Authors: Ruth E Taylor-Piliae, L. Daniel Latt, Bruce M Coull
Journal: Circulation (2012)

Background: Gait velocity is an objective, fundamental indicator of post-stroke walking ability. Most stroke survivors have diminished aerobic endurance and paretic leg strength, with one or both of these conditions affecting their gait velocity. Other reported underlying factors affecting gait velocity include functional disability, balance and cognitive impairment. Objective: To examine potential independent predictors of gait velocity in chronic stroke. Methods: Cross-sectional design using baseline data from the first 100 community-dwelling stroke survivors enrolled in an exercise intervention study. Eligible subjects included men and women aged ≥ 50 years and at ≥ 3 months post-stroke. Subjects completed a comprehensive, self-administered health survey prior to their baseline study visit. At the baseline visit, functional disability (Modified Rankin Scale), aerobic endurance (2-minute step-test), leg strength (timed 5-chair stand test), balance (single-leg stance) and cognitive impairment (Mini-Mental Status Exam) were assessed. Gait speed was assessed using a valid and reliable timed 4-meter walk test designed for older adults with disabilities; to calculate gait velocity (meters/second). Multiple linear regression was conducted to explore potential independent predictors of gait velocity. Results: Subjects (n=100) were on average 70±10 years old, and 39±49 months post-stroke. The majority reported an ischemic stroke (68/100) with hemiparesis (80/100); and were married (59/100), White/European-American (78/100), college-educated (79/100), men (54/100). Subjects had an average gait velocity of 0.75±0.23 meters/second, categorized as limited community walkers. Approximately 37% of the variance in gait velocity, could be explained by the optimal combination of the independent variables in the model: functional disability, aerobic endurance, leg strength, balance, and cognitive impairment (R 2 =0.37, F 5,74 =8.64, p&lt;0.01). Only better aerobic endurance (t 1,74 =3.41, p&lt;0.01) and leg strength (i.e. faster chair stand time) (t 1,74 =–2.23, p=0.03) contributed uniquely and significantly to faster gait velocity. Conclusion: A hallmark of gait dysfunction in chronic stroke is slow gait velocity, even among well-educated, community-dwelling survivors. Gait velocity is simple to measure requiring only a stopwatch and flat surface for walking. Our findings are similar to reports by others that diminished aerobic endurance and leg strength are major contributors to slow gait velocity in chronic stroke. Long term rehabilitation efforts are needed to improve gait velocity in chronic stroke, and may need to incorporate multifaceted strategies concurrently, focusing on aerobic endurance and leg strength, to maximize community ambulation and reintegration.
Effect of Simian Virus 40 Subcutaneous Tumors on Circulating Lipids and Lipoproteins in the Syrian Hamster
Authors: R A Cox, M Gökcen
Journal: JNCI Journal of the National Cancer Institute (1975)

Circulating lipid levels and lipoprotein patterns in the Syrian hamster were determined at various times after subcutaneous inoculation with simian virus 40 (SV40) strain F, strain A-2895, or Fortner melanoma tumor cells. SV40 F tumors induced a rapid triphasic elevation of serum total lipids through inhibition of prebeta lipoprotein catabolism. Alpha lipoprotein levels declined in proportion to tumor mass. Liver wet weight and total lipid content increased significantly, but a normal rate of 3H-glycerol incorporation into polyanion precipitable (prebeta) serum lipoprotein was maintained. Determination of serum endogenous lipase, lecithin:cholesterol acyltransferase (LCAT), and cholinesterase activities indicated that these enzymes were not primarily responsible for the tumor-induced hyperlipidemia. Tumor-bearing animals also had selectively increased rates of protein and lipid excretion into the urine, with no evidence of gross hepatocellular or kidney damage. Growth of SV40 A-2895 tumors in hamsters resulted in a large increase in the rate of prebeta lipoprotein synthesis and degradation. Circulating prebeta lipoprotein levels were elevated much later in these animals, subsequent to a marked decrease in LCAT activity. Quite different results were obtained with Fortner melanoma, even large tumors having only a moderate effect on serum total lipid levels and lipoprotein patterns in the Syrian hamster.
Impaired Inflammatory Response in Tumor-Bearing Guinea Pigs
Authors: Irwin D. Bernstein, Berton Zbar, Herbert J. Rapp
Journal: JNCI Journal of the National Cancer Institute (1972)

Guinea pigs with large intramuscular tumors showed impaired delayed cutaneous hypersensitivity to specific antigens and decreased skin inflammatory reactivity to nonspecific agents. Induced peritoneal exudates from these animals contained fewer cells than those obtained from tumor-free animals. The number of peripheral blood leukocytes in tumor-bearing animals was normal or increased, and the turnover rates for monocytes and polymorphonuclear leukocytes were increased. However, in vitro, lymphocytes from animals with tumors responded to antigen as measured by increased DNA synthesis and the production of skin reactive factor. The defect in skin reactivity may be due to an impairment of one or more factors related to immunologically nonspecific components of cell immunity.
Extensive-disease small-cell lung cancer: the thrill of victory; the agony of defeat.
Authors: J Aisner
Journal: Journal of Clinical Oncology (1996)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1996.14.2.658 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8636784 Extensive-disease small-cell lung cancer: the thrill of victory; the agony of defeat. J AisnerxJ AisnerSearch for articles by this author Show More Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, USA. https://doi.org/10.1200/JCO.1996.14.2.658 First Page PDF © 1996 by American Society of Clinical Oncology
Impact of adjuvant chemotherapy prior to endocrine therapy: 68 month results from the ‘Arimidex’, Tamoxifen, Alone or in Combination (ATAC) trial
Authors: A. U. Buzdar
Journal: Journal of Clinical Oncology (2005)

608 Background: Previous analyses of the ATAC trial demonstrated initial adjuvant treatment with anastrozole (A) has significant efficacy and tolerability advantages over tamoxifen (T). At 33 months’ median follow-up there was a potential interaction with previous chemotherapy, which was less apparent at 47 months’ median follow-up. When the effects of different chemotherapy regimens were retrospectively evaluated at 47 months, the apparent interaction was limited to patients who had received cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Here we evaluate the results from the ATAC trial at 68 months’ median follow-up to assess the effect of different chemotherapy regimens on time to recurrence (TTR) over the full 5-year treatment period. Methods: Chemotherapy regimens were (1) CMF, (2) anthracycline (AC)-containing regimens (AC, cyclophosphamide ± 5-fluorouracil), (3) other chemotherapies, including taxane-containing combinations. The impact of regimens on TTR was calculated and expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Consistent with the 47-month analysis, superiority for TTR was maintained for A versus T in the AC-containing and taxane-containing subgroups. Advantages for A are now evident with CMF. Adjusting for chemotherapy type had only a minimal effect on TTR. Conclusions: Despite the previously reported interaction within the CMF-group, additional follow-up has confirmed that the benefits of A over T are maintained regardless of the type of chemotherapy given. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca
Bone and soft tissue response from a phase I/II study with ODM-201 in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Jorge A. Garcia, Vesa V Kataja, Nicholas David James, Robert Hugh Jones, Andrew Protheroe, Christophe Massard, Leena Mattila, Mika VJ Mustonen, John Aspegren, Karim Fizazi
Journal: Journal of Clinical Oncology (2014)

102^ Background: ODM-201 is a novel potent full androgen receptor (AR) inhibitor for CRPC. ODM-201 has excellent nonclinical efficacy in xenograft studies and high PSA response rate in CYP17i-naïve CRPC patients in the phase I/II ARADES study. Methods: To further analyze clinical efficacy of ODM-201 in CRPC pts we evaluated the overall response rate (ORR) in ARADES phase I/II study (Fizazi et al. Abstract #2853, ECC2013, Amsterdam 28 Sept 2013 ).Patients (pts) were enrolled into three dose levels 100mg bid, 200mg bid and 700mg bid. Results: All eligible 124 pts had progressive mCRPC; 37 pts were pre-chemo/CYP17i-naïve, 32 post-chemo/CYP17i-naïve and 55 post-CYP17i. Thirty-two (86%) pts in the pre-chemo/CYP17i-naïve group, 27 (84%) post-chemo/CYP17i-naïve and 48 (87%) post-CYP17i had bone disease at baseline. Similarly, twenty-two (29%) pts, 19 (59%) and 36 (65%), respectively had RECIST-define measurable disease. Median baseline PSA was 101ng/mL (3-1294) in pre-chemo/CYP17-i-naïve group, 94ng/mL (8-663) in post-chemo/CYP17-i-naïve group, and 139ng/mL (9-5000) in post-CYP17i group. CTC count was over 5CTCs per 7.5ml in 43% of the pts in pre-chemo/CYP17-i-naïve group, 41% in post-chemo/CYP17-i-naïve group and 44% in postCYP17i group. ORR data is presented in table below. Conclusions: Although RECIST-define responses were observed across the 3 different group of pts treated with ODM-201 the vast majority of pts had RECIST-defined SD up to 12 weeks. These data are in line with PSA data reported previously that demonstrate the clinical activity of ODM-201 in men with mCRPC. Clinical trial information: NCT01317641, NCT01429064. [Table: see text]
A randomized trial comparing 12 weeks versus 36 weeks of adjuvant chemotherapy in stage II breast cancer.
Authors: M N Levine, M Gent, W M Hryniuk, V Bramwell, H Abu-Zahra, S DePauw, A Arnold, B Findlay, L Levin, J Skillings
Journal: Journal of Clinical Oncology (1990)

A randomized trial has been performed in which women with axillary node-positive breast cancer were allocated to either a short intensive 12-week chemohormonal treatment consisting of cyclophosphamide, methotrexate, fluorouracil, vincristine, prednisone, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and tamoxifen (CMFVP plus AT) or 36 weeks of CMFVP. The median follow-up is 37 months. Of the 222 women randomized to the 12-week treatment, 113 (50.9%) have experienced either recurrence or death as compared with 90 patients (41.9%) in the 36-week treatment group. The corresponding 3-year relapse-free survivals are 55% and 64%, respectively, P = .003. Fifty-nine (26.6%) of the patients in the 12-week group have died compared with 46 (21.4%) of the 36-week group. The corresponding 3-year survival rates are 78% and 85%, respectively, P = .04. A Cox regression analysis showed an associated increased risk ratio for recurrence or death of 1.7, P = .003, and for death of 1.8, P = .017 in the 12-week treatment group compared with the 36-week group. Thus, this 12-week regimen of adjuvant chemohormonal therapy is inadequate treatment for women with axillary node-positive breast cancer; possible explanations for this inferiority are its shorter duration and/or a negative interaction of tamoxifen on the chemotherapy.
Tolerance of avastin in metastatic colorectal cancer—a single institute Kuwait Cancer Control Centre experience
Authors: V. Vyas, S. A. Awadi, A. E. Khodary, J. Nemec, K. C. Muralidharan, M. D. Delvadiya
Journal: Journal of Clinical Oncology (2007)

14156 Background: Bevacizumab is being used in combination with five fluorouracil(5-FU) based chemotherapy like FOLFIRI, FOLFOX, and capecitabine, since its inception in the treatment of metastatic colorectal cancer one year ago. Methods: a retrospective analysis was carried out to assess the toxicity profile of bevacizumab. Results: total 36 patients received bevacizumab in combination with various 5-FU based regimens .Twenty one were males 15 were females. A total of 288 cycles have been administered. Toxicities included change in medication for uncontrolled hypertension and mild epistaxis in 3 cases. One patient with intact primary in sigmoid colon developed perforation, peritonitis and she died subsequently. Conclusions: Conclusion- this preliminary results indicate that bevacizumab in combination with 5-FU based chemotherapy was tolerated. Extra precaution is required in cases of intact primary tumours. No significant financial relationships to disclose.