tbuckley/cabot-search huggingface dataset:
Gemcitabine + cisplatin (GEM+CIS) in combination with regional hyperthermia (RHT) in second-line therapy of gemcitabine-refractory metastatic pancreatic cancer
Authors: K. E. Tschoep, V. Milani, G. Schmidt, X. Schiel, S. Abdel-Rahman, M. F. Kuhlencordt, C. Salat, V. Maier, V. Heinemann, R. D. Issels
Journal: Journal of Clinical Oncology (2006)

14073 Background: Our completed phase III trial comparing GEM + CIS vs. GEM alone showed good efficacy for the combination arm in 1st-line therapy (ASCO abstr. No. 1003, 2003). Based on the rationale of chemosensitization of CIS by RHT we are performing a prospective phase II study with GEM + CIS combined with RHT. Methods: Until 8/2005 12 pts with metastatic pancreatic adenocarcinoma who failed GEM-based 1st-line-therapy were enrolled in this study. One cycle consisted of GEM (1000mg/m 2 ) on d1 followed by CIS (25mg/m 2 ) on d2 and d4 combined with RHT (BSD system). A total of 2 blocks each of 4 cycles were given biweekly. The main endpoints were time to second progression (TTP2) and 1-year event free survival (1-yr-EFS). TTP2 and EFS were defined as time from start of 2nd-line therapy until progression of disease or death. Response (RECIST) was evaluated after 4 and 8 cycles of therapy. Results: Pt characteristics: median age 60; M:F=8:4. Median time to first progression (TTP1) was 6 months (95% CI:2–7). 8/12 pts received all 8 cycles. No toxic death and no grade 4 toxicity occurred. In 12/2005 10/12 pts were evaluable for this study. Control of disease (1CR, 2MR, 4NC) and progression (3PD) occurred in 70% and 30% respectively. The median TTP2 is 8 months (95% CI: 2–13) and the 1-yr-EFS is 32% (95% CI:3–61). 7 pts are alive at 12/2005. Conclusions: Our ongoing study (EudraCT-No 2005–003855–11) using RHT combined with GEM + CIS shows promising antitumor activity with a very encouraging TTP2 and median 1-yr-EFS in the 2nd-line treatment of GEM-refractory metastatic pancreatic cancer. [Table: see text]
Design of the AFFINITY study: A randomized phase III study of a novel clusterin inhibitor, custirsen, plus cabazitaxel/prednisone (CbzP) versus CbzP alone as second-line chemotherapy in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Tomasz M. Beer, Brent A. Blumenstein, Karim Fizazi, Sebastien J. Hotte, Cindy Jacobs, Patricia S. Stewart
Journal: Journal of Clinical Oncology (2013)

TPS5103 Background: Custirsen enhances chemotherapeutic activity via inhibition of clusterin expression. Clusterin is a cytoprotective, antiapoptotic chaperone upregulated by anticancer therapies that confers treatment resistance. In a phase 2 study, mCRPC patients who had progressed within 6 mos of completing first-line docetaxel (DOC)/prednisone (P) and who were retreated with DOC/P and custirsen had a median overall survival of 15.8 mos. Lowering of serum clusterin level during second-line treatment was associated with significantly longer survival. CbzP has recently shown a survival advantage in patients with prostate cancer that has progressed after DOC therapy. The AFFINITY study was designed to evaluate in a larger study whether adding custirsen to CbzP will further improve survival in this patient population. Methods: AFFINITY was initiated in August 2012. Eligible patients in this phase 3, international, multicenter, open-label trial must have received ≥225 mg/m 2 of DOC; have progressive disease as defined by RECIST 1.1, bone scan progression, and/or serum prostate-specific antigen level; have metastatic disease of the chest/abdomen/pelvis/bone; have adequate renal and liver function; and have a Karnofsky score ≥70%. Patients may have received up to 1 DOC regimen as well as abiraterone and/or enzalutamide. Approximately 630 patients will receive 21d cycles of Cbz (25 mg/m 2 IV q21d) + P (10 mg PO/d), either alone or with custirsen 640 mg IV given for 3 loading doses and then weekly until disease progression, unacceptable toxicity, or 10 cycles. The primary efficacy measure is overall survival. The secondary measure is proportion of patients alive without disease progression at Day 140 post-randomization. All efficacy analyses are intent to treat. Adverse events of all patients who receive ≥1 dose of custirsen or Cbz will be included in the safety analysis. This study is sponsored by Teva BPP R&amp;D, Inc., in collaboration with OncoGenex Pharmaceuticals, Inc. Clinical trial information: NCT01578655.
Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome.
Authors: F M Foss, D C Ihde, I R Linnoila, A B Fischmann, G P Schechter, J D Cotelingam, S M Steinberg, B C Ghosh, J L Stocker, A Bastian
Journal: Journal of Clinical Oncology (1994)

This phase II study was undertaken to assess the efficacy and toxicity of the addition of continuous low-dose interferon alfa-2a (IFN) to fludarabine in patients with advanced or refractory mycosis fungoides (MF) or the Sézary syndrome (SS).Thirty-five patients were treated with fludarabine 25 mg/m2 intravenously (IV) on days 1 to 5 every 28 days along with IFN 5 x 10(6) U/m2 subcutaneously three times per week continuously for up to eight cycles. IFN doses were escalated to 7.5 x 10(6)/m2 at day 29 if constitutional toxicities were less than grade 3. Twenty-one patients had not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), and 10 of these had received prior deoxycoformycin (pentostatin; DCF) and intermittent high-dose IFN; seven had received only topical therapies, and seven were untreated.Four patients achieved a complete response (CR) and 14 achieved a partial response (PR) for an overall response rate of 51% (95% confidence interval, 35% to 70%). Four of 11 patients with visceral involvement responded. The median progression-free survival duration of the patients who responded was 5.9 months, and three of the complete responders are in unmaintained response after 18 to 35 months. Grade 3 or 4 hematologic toxicity occurred in 21 patients, including two who developed persistent bone marrow aplasia. Eighteen patients developed infections during therapy, including five with herpes zoster, one with Pneumocystis carinii, one with extrapulmonary tuberculosis, and two with disseminated toxoplasmosis.The combination of fludarabine with continuous low-dose IFN is an active regimen in patients with advanced MF/SS, including patients with visceral involvement and patients who progressed after prior therapy with DCF and IFN. This regimen has induced unmaintained remissions in a small subset of patients.
Mortality rate with irinotecan/cisplatin plus concomitant radiation therapy in patients with locally advanced esophageal squamous cell carcinoma
Authors: G. Geib, M. W. Machado, B. Pozzi, N. S. Lazaretti, C. Dutra, M. N. Pereira Lima, P. R. Ferreira, S. J. Azevedo, G. Schwartsmann
Journal: Journal of Clinical Oncology (2009)

e15560 Background: The cisplatin/irinotecan doublet plus concomitant radiation therapy has been tested in phase II studies as a non-infusional alternative for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC), showing good antitumoral activity and acceptable safety profile. Here, we describe our institutional experience with this combination, specially regarding its toxicity profile. Methods: A series of 26 patients with locally advanced, unresectable ESCC patients treated at our institution between September/2006-January/2008 is reported. Treatment consisted of cisplatin 30 mg/m2 and irinotecan 65 mg/m2 on weeks 1, 2, 4, 5, 8, 9, 11 and 12, and radiation therapy (50,4 Gy, 1,8 Gy/day) on weeks 8–12. Study endpoints were tumor response rate (RECIST), safety profile (CTCAE v3), overall and one year survival. Results: The mean age of patients was 61 years, with stage III disease in 88% of cases and performance status (ECOG) 0–1 in 90% of them. Twenty patients (77%) were available for response, with complete response, partial response/stable disease and progressive disease seen in 40%, 45% in 15% of cases, respectively. With a median follow up of 20 months, the overall survival was 9,2 months and the one-year survival 34,6%. All patients were evaluable for toxicity, with severe (grade 3–4) nausea/vomiting, diarrhea, neutropenia and thrombocytopenia documented in 45%, 33%, 18% and 13% of cases, respectively. Notably, treatment related deaths were observed in 5 cases (19%), mainly due to infectious complications, which led to the closured of this protocol due to excessive toxicity. Conclusions: In spite of its promising antitumor activity, this treatment regimen cannot be recommended for routine use due to its unacceptable treatment-related mortality. No significant financial relationships to disclose.
Thymidylate synthase gene expression in solid tumors predicts for response to pemetrexed in vitro
Authors: U. Eismann, O. Oberschmidt, M. Ehnert, J. Fleeth, F. Lüdtke, S. Struck, L. Schulz, J. Blatter, D. Ma, A. Hanauske
Journal: Journal of Clinical Oncology (2006)

13058 Background: Pemetrexed (P) is a novel antifolate which targets thymidilate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). The aim of the present study was to identify gene expression thresholds for these enzymes in human tumor specimens in order to separate P-sensitive from P-resistant patients. Methods: Soft-agar cloning assays were performed on freshly biopsied tumor cells exposed one hour to clinically achievable concentrations of P. In parallel, RNA was isolated, transcribed to cDNA and subsequently used for multiplex real-time PCR. Gene expression data were normalized against beta-actin transcripts followed by correlation against cloning assay results. Iterative calculations (fourfold analysis) were done for each enzyme separately to find the best cutoff for prediction of sensitivity to P. Results: Sensitive and resistant tumor samples were statistically significant different in gene expression of TS, DHFR, and GARFT (p &lt; 0.003). 81% of all tumors with a TS copy number &lt; 144 (related to 10 4 copies β-actin) were sensitive to P in vitro. (specificity = 0.69; chi 2 = 14.14). Statistical tests demonstrated that gene expression of TS, DHFR, and GARFT are dependent variables and that TS transcription is the leading variable. The combination of TS, DHFR, and GARFT expression data was not superior to TS alone. Conclusions: TS expression is the most meaningful predictor for sensitivity (≤ 144 copies) or resistance (&gt; 144 copies) to Pemetrexed in fresh tumor tissue. This observation forms a rationale for clinical trials using TS expression as predictor for clinical response. No significant financial relationships to disclose.
Abstract 18356: Are Soluble Receptors of Advanced Glycation End Products Associated with Pre-clinical Diastolic Dysfunction in Patients with Diabetes?
Authors: Terase F Lancefield, Bryan Wai, Sheila K Patel, Elena Velkoska, Michelle Ord, Piyush M Srivastava, Louise M Burrell
Journal: Circulation (2012)

Background: Pre-clinical diastolic dysfunction is common in diabetes. The parameter, E/e (ratio of the early mitral inflow (E) to septal mitral annular velocity (e) in diastole) is a continuous variable that correlates with increased LV filling pressure. In retrospective studies in diabetes, an E/e &gt;15 predicted mortality and heart failure (HF). The soluble receptor of advanced glycation end products (sRAGE) and the splice variant, endogenous secretory RAGE (esRAGE) have been proposed as biomarkers of systolic HF in diabetes. This prospective study investigated the relationship between sRAGE, esRAGE and pre-clinical diastolic function in patients with diabetes. Methods: We recruited 263 patients with diabetes attending for a transthoracic echocardiogram as part of a complications surveillance program. Pre-clinical diastolic dysfunction was defined as an E/e &gt;15. Patients with LVEF &lt;50%, coronary artery disease, history of HF and significant valve pathology were excluded (n =86). Serum levels of sRAGE and esRAGE were measured using an ELISA. Data are presented as mean ±SD for parametric variables and geometric mean (25, 75th quartile) for non-parametric variables. Results: Patients with an elevated E/e’ were significantly older (69 ±10 vs. 59 ±13y, p &lt;0.001) and were more likely to have hypertension (97 vs. 75%, p = 0.002) and a reduced eGFR &lt;60ml/min/1.73m2 (47 vs. 14%, p &lt;0.001). Gender, HbA1c and other cardiac risk factors were similar. Levels of sRAGE and esRAGE (geometric mean (25, 75th quartile) are shown below. Serum sRAGE remained significantly associated with an elevated E/e’ after adjustment for age, gender, BMI, diabetes duration, hypertension and renal function (p=0.015). Conclusions: Serum levels of sRAGE but not esRAGE are associated with pre-clinical diastolic function assessed in patients with diabetes. Follow up studies are underway to assess if an elevated sRAGE predicts the development of overt HF in this cohort of patients with diabetes.
Tolerance to treatment in elderly patients with colon cancer
Authors: N. G. Pilnik Prof, M. A. Ibero
Journal: Journal of Clinical Oncology (2009)

e20710 Background: About 60% of all colorectal cancers occur after the age of 50. This tumor is the second most common cause of cancer and the death by neoplasm. Beside, aging may affect several aspects of pharmacology due to a progressive reserve deteriorations and the comorbidities presence which may influence the tolerance to treatment. Methods: 90 colorectal cancer pts, aged 65–78 years, who underwent surgery and Ch/Rt were included . Pts were divided in two groups: I: ≤ 70 and II &gt; 70 years. Pts selection was conducted using General Geriatric Assessment . All pts had adequate cardiac, hepatic, renal and bone marrow functions. Comorbidities studied were: hypertension, diabetes, COPD, cardiac disease,and gastrointestinal disease.Toxicities were studied following the WHO criteria and correlated according to age, Activity of Daily Living (ADL),Instrumental Activity of Daily Living (IADL), PS, WL, comorbidities, and the use of more than 3 drugs in addition to Ch/ Rxt. QoL was studied through the evaluation of ADL, IADL, and PS evolution. Statistical Methods: Pearson´s Chi-Square test, Kaplan Meier´s curves. Results: The most frequent level in the whole sample was Grade I. No relationship was found between toxicities and age. Toxicity level was found to be higher in the pts who used more than 3 other medications p=0,01. Statistically significant association was found between comorbidities and toxicity levels p = 0,04. WL and toxicity level were statistically associated, p = 0,01. There was improvement in Qol through the evaluation of ADL, PS,and IADL evolution p= 0.03. PS and IADL were statistically correlated with survival p = 0.02 Conclusions: Older Colon cancer pts in good general condition and with controlled comorbidities may receive Ch/ Rxt. The reason why the majority of pts had low toxicities may be attributed to the fact that all of them were properly selected. No significant financial relationships to disclose.
Pilot evaluation of citalopram for alleviation of hot flashes in women with inadequate hot flash control with venlafaxine
Authors: L. A. Carpenter, C. L. Loprinzi, P. J. Flynn, P. J. Atherton, D. L. Barton, T. D. Shanafelt, T. A. Rummans, J. A. Sloan, A. A. Adjei, B. A. Mincey
Journal: Journal of Clinical Oncology (2005)

8061 Background: While venlafaxine does alleviate hot flashes, it provides inadequate relief for some patients. To determine whether another antidepressant might alleviate hot flashes in such women, the current pilot trial was conducted. Methods: Women who had been on therapy with venlafaxine (75 mg/day), who were experiencing at least 14 hot flashes/week, and who wished to pursue other pharmacologic therapy because of inadequate benefit from venlafaxine were enrolled on this trial. Participants kept a daily hot flash diary during a baseline week (continuing venlafaxine for this week if they were still on it, 16 patients) and then also during four treatment weeks while receiving citalopram in the following manner: 10 mg/d for one week, then 20 mg/d for three weeks. A total of 30 patients were entered on this study between 8/29/03 and 2/27/04. Results: Complete hot flash information, currently available for 22 study patients, are provided in the table, illustrating hot flash score (daily frequency times average severity) data during the fourth treatment week compared to the baseline week (where patients had a mean of 8.8 hot flashes/day with a mean hot flash score of 16.8/day). Citalopram was well-tolerated, with most patients reporting an improvement in several measured symptoms over baseline. Following completion of the study, patients were given the choice of staying on citalopram. Nineteen patients (63% of pts entering the study, 86% of pts completing the 5 week study period) chose to continue it. Conclusions: These preliminary data support citalopram as a potentially effective alternative agent for managing hot flashes in women for whom venlafaxine provides inadequate relief. No significant financial relationships to disclose.
Estrogen receptor in HER2-positive early breast cancer: Two different diseases?
Authors: Eva Maria Ciruelos Gil, Ismael Ghanem, Luis Manso, Sergio Hoyos, Carlos Castañeda, David Lora, Cesar Mendiola, Blanca Sancho, Tomas Pascual, Hernan Cortes-Funes
Journal: Journal of Clinical Oncology (2012)

642 Background: HER2+ breast cancer (BC) is a well characterized subtype of BC, due to the predictive value of HER2 overexpression for anti-HER2 targeted therapies. Nevertheless, around 50% of HER2+ BC are ER+ and clasiffied as luminal B/HER2+, but their biological and clinical behaviour may be different from HER2+/ER- tumors. Methods: We retrospectively reviewed 347 HER2+ (Herceptest +++ or FISH+) early BC patients (see Table) diagnosed at our institution in 1997-2007, and were divided into two study groups: HER2+/ER+ (group A) and HER2+/ER- (group B). ER+ was defined if expressed in &gt; 10% tumor cells. Results: See table below. Mean age: 54.7 y (44.6 – 65). Mean Ki 67 was higher in B (37,2 vs 22,4%, p&lt;0.0001). At the current FU, n¼ of events were insufficient to reach median DFS/OS. Mean DFS was 6.9 y (3.5 – 10.2); recurrent disease was higher (p 0.003) for B (54 pts, 43%) vs A (62 pts, 28%). 5-year DFS estimates: 78.4 % (95% CI 72.3 – 83.3) and 62.3 % (95% CI 53 – 70.27) for A and B, and 10-year DFS was 73.4% (95% CI 66.6 – 79) and 52.5% (95% CI 42.4 – 61.6) for A and B, respectively (p 0.0006). Most common recurrent sites were local (18) and bone (9) for HER2+/ER+ and liver (8) and lung (8) for HER2+/ER-. Mean OS was 8.03y (5.4 – 10.8); 28 (12,6%) pts died in A, vs 26 (21%) in B (p 0.043). 5-year OS estimates: 93.9 % (95% CI 89.7 – 96.4) and 87.6 % (95% CI 80.3 – 92.3) for A and B, and 10-year DFS was 84.2% (95% CI 77.5 – 89.0) and 74.1% (95% CI 63.4 – 82.2) for A and B, respectively (p 0.01). Conclusions: ER expression in HER2+ early BC defines two clinically distinct diseases with different long-term prognosis. These data may help to better individualize adjuvant therapies and future clinical trial designs. [Table: see text]
A prospective evaluation of the patients' knowledge about their chemotherapy treatment (CT) before the first course.
Authors: N. Kohen, E. L. Morgenfeld, C. Garcia Gerardi, M. Nacul, C. Coronel Lezcano, E. Rivarola, E. Gil Deza, N. Gercovich, F. G. Gercovich
Journal: Journal of Clinical Oncology (2010)

6089 Background: The first CT cycle is usually associated with fear and hopelessness. This stress could impact the doctor-patient communication. With the aim of evaluating patient knowledge on the therapy and side effects before the administration of the first CT cycle, the Nurse Department of the Henry Moore Institute developed a survey, the results of which are listed in this paper. Methods: The survey was designed to evaluate four topics: Pt's general knowledge on their therapy (1 question); CT toxicity (7 questions); lifestyle during CT (3 questions) and supportive therapies (4 questions). All the answers were of a yes/no basis (adequate/inadequate). They were tabulated and each frequency distribution was analyzed. Results: Sixty-eight consecutive patients received the first CT cycle and completed the survey at IOHM between November 1, 2009 and November 30, 2009. Population characteristics: gender: female 35/68 (50.2%), age: mean 57 yo (range 20-79 yo), diagnosis: breast (25%), colon (20%), lung (8%), lymphoma (5%). Twenty-four patients responded affirmatively to all fifteen questions, 44 patients had one or more negative answers. In each of the topics, the following trend among negative answers were observed: general knowledge 3/68; toxicity: asthenia 1/68, alopecia 2/68, diarrhea 4/68, lab results 4/68, immunodeficiency 18/68; lifestyle: sun exposure 1/68, makeup and hair dye 19/68, sexuality 6/68; medical indications: diet 4/68, daily liquid requirements 4/68, support medication 5/68, analgesics 4/68. Conclusions: (a) In spite of the efforts taken to enhance communication between patients and doctors, 44/68 (65%) patients underwent their first chemotherapy cycle with inadequate knowledge on some practical aspects of CT (b) As a result of this work, two instruments to improve patient knowledge have been designed: a checklist to fill in by the doctor, and a short educational intervention from oncologic nurses after the first CT cycle to reinforce practical tips. The result of these interventions will be presented at the meeting. No significant financial relationships to disclose.
ABCF2 is a new biomarker of ovarian clear cell adenocarcinoma
Authors: S. Nishimura, H. Tsuda, Y. M. Ito, K. Ito, N. Yaegashi, M. J. Birrer, Y. Ohashi, Y. Hashiguchi, R. S. Berkowitz, S. C. Mok
Journal: Journal of Clinical Oncology (2005)

5050 Background: Epithelial ovarian cancer (EOC) can be subdivided into five major histologic types (Serous(SC), Mucinous(MC), Endometrioid(EC), Clear cell(CC), Undifferentiated (UC)). Among them, CC generally has a poor response to combination chemotherapy and its overall prognosis is poor. The CC and EC are thought to arise from endometriosis (EM), while a majority of SC are thought to arise from inclusion cysts. In previous reports, we compared gene expression between CC and SC using cDNA microarrays and suggested that ABCF2, which is a new member of the ATP-binding cassette transporter superfamily, gene might be a new biomarker for CC (Proc ASCO 2003 22:448a). In this study, we generated a polyclonal antibody for ABCF2 and further validated the expression of ABCF2 in EOC and EM. Methods: Formalin-fixed surgical samples from 307 EOC and 20 EM patients were included in this study. ABCF2 expression was investigated by immunohistochemostry. The percentage of positive cytoplasmic staining (PCS) for ABCF2 was calculated by examining at least 1000 tumor cells. In 28 cases, quantitative RT-PCR was performed to evaluate the relationship between ABCF2 protein expression and relative mRNA expression. Results: Histologic types, stage and grade were as followed: (SC: 93; MC: 46; EC: 56; CC: 80; UC: 32, EM: 20), (I: 109; II: 34; III: 141; IV: 23) and (GR1: 110; GR2: 90; GR3: 106). In EOC, 166 of 307(54%) cases had ABCF2 expression and relative mRNA expression significantly correlated with levels of ABCF2 protein expression (r=0.504, p=0.006). The relationship between ABCF2 expression and histologic type was shown in table. CC had significantly higher levels of ABCF2 expression than that of other histologic types The positivity rate of ABCF2 in CC was significantly higher than other histologic type. However, there is no significant correlation between ABCF2 expression status and histologic stage or grade. In EM, ABCF2 expression was detected in 6 of 20 cases. Conclusions: ABCF2 expression is a new biomarker for CC. No significant financial relationships to disclose.