tbuckley/cabot-search huggingface dataset:
Comparison of outcome in erythroleukemia patients treated with standard chemotherapy regimens or hypomethylating agents.
Authors: C. E. Vigil, W. Tan, G. E. Wilding, G. Garcia-Manero, E. S. Wang, M. Wetzler, A. F. List
Journal: Journal of Clinical Oncology (2011)

6630 Background: Erythroleukemia is a rare form of acute leukemia often accompanied by unfavorable cytogenetics. Traditionally treated with a standard cytarabine–based induction regimen, median survival is poor (~8 months). Due to its rarity few studies have outcomes with alternate treatments. Hypomethylating drugs had demonstrated clinical activity in patients with poor risk myelodysplastic syndromes (MDS) with improved overall survival compared to best supportive care. Methods: Retrospective review from 33 patients with erythroleukemia treated with either hypomethylating agents (at three different institutions: MD Anderson Cancer Center, Moffitt Cancer Center and Roswell Park Cancer Institute since November 2002) and comparison with standard of care. Results: The median age was 67 years (range, 38-84), 9 (27%) were females. Treatment was with azacytidine (AZA) in 12 (36%) and with decitabine (DAC) in 9 (27%) of the cases. 12 patients received therapy with cytarabine-based chemotherapy agents as induction. Cytogenetic analysis included diploid in 9, complex abnormalities in 19 and intermediate risk in 5. FLT3 mutations were absent in all 16 patients tested. Fourteen (67%) of the 21 patients treated with hypomethylating agents achieved a complete remission (CR) whereas five (42%) patients treated with induction chemotherapy; this was accompanied by complete cytogenetic remission in 14 of 16 evaluable patients. The median number of cycles to achieve CR was 3 (range, 2 to 4). After a median follow up of 8 months (range,1-58) the median overall survival time was 15.4 months (95%CI: 7.1 to 24.8) in those who receive hypomethylating agents versus 10 months (95%CI: 1.6 to 15.4) in those who did not (P=0.0322). Conclusions: These results suggest that hypomethylating agents are highly active in patients with acute erythroleukemia and may extend survival compared to standard induction chemotherapy regimens. Benefit from high intensity therapy is limited, suggesting biological overlap with MDS.
Cell-selective oligonucleotide STAT3 inhibitor for immunotherapy of human acute myeloid leukemia
Authors: Qifang Zhang, Sakib Hossain, Dayson Moreira, Priyanka Duttagupta, Xingli Zhao, Piotr Swiderski, Marcin Kortylewski
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts STAT3 transcription factor is persistently activated in cancer cells and in diverse tumor-associated immune cells being an important oncogene and an essential immune checkpoint regulator. It is a highly desirable but challenging therapeutic target for pharmacological intervention
Lapatinib plus capecitabine in highly pretreated HER2-positive metastatic breast cancer: A single-institution experience.
Authors: D. Crivellari, S. Spazzapan, M. Magri, S. Frustaci, R. Talamini, D. Lombardi, E. Torrisi, S. Scalone, G. Miolo, A. Veronesi
Journal: Journal of Clinical Oncology (2010)

1145 Background: Therapies targeting HER2 are very effective in metastatic breast cancer (MBC) combined with chemotherapeutic agents (CAs). Lapatinib (L) demonstrated activity and improved time to disease progression in pts who had progressed on trastuzumab (T) (Cameronet al 2008). Since April 2007, L in combination with capecitabine (X) was available in Italy within an expanded access program and thereafter as commercial drug. Methods: From April 2007 to March 2009, 58 HER2-positive MBC pts who had developed progression after antracycline-, taxane-, and T-based regimens, were treated with L plus X in our Institution. Results: Fifty-seven pts were evaluable for response. The median number of previous treatment lines, including the adjuvant setting, was 3 (ranging from 1 to 7). The median duration of previous T treatment (given alone or with chemotherapy) was 19 months (range 2.5-57 months). The median time to progression (MTTP) after first line T plus a cytotoxic agent (CA) was 11 months. At progression, 40 pts (69%) had visceral disease and in particular 8 pts (14%) had brain metastasis. The median number of cycles of L-X was 7 (range 2-29+ cycles). MTTP after L-X was 5,3 months. Clinical benefit (CB) (defined as complete remission plus partial remission plus stable disease lasting for at least 6 months) was noted in 33 pts (57%) with 4 pts having long lasting CR in visceral sites. The most frequent nonhematological toxicity was diarrhea and hand-foot syndrome. No G4 toxicity was noted. Conclusions: The combination of L and X is confirmed to be an active regimen even in highly pretreated HER2-positive MBC pts and in pts with visceral and brain metastases. Unfortunately the toxicity of both agents appears to be partly overlapping, even if only few pts experienced severe toxicities. Comparative studies with other CAs appear to be warranted. No significant financial relationships to disclose.
Long-term use of sorafenib (SOR) in metastatic renal cell carcinoma (mRCC) previously treated with systemic therapy
Authors: M. Battaglia, A. Gernone
Journal: Journal of Clinical Oncology (2009)

e16123 Background: The recent development of new targeted agents for the treatment of advanced RCC has definitely changed the approach and the outcome of this disease. Among them, SOR, has proved to be highly active in the treatment of mRCC. The aim of this study was to assess the activity and the safety of SOR in pts with mRCC relapsed after prior systemic therapy. Methods: Between 2/2007 and 10/2008, 22 pts with mRCC relapsed after 1–2 prior lines of chemotherapy (gemcitabine, vinorelbine, 5-FU) have been treated with SOR orally administered at the dose of 400mg b.i.d. continuous dosing. They were18 males and 4 females, with a median age 67 years, an ECOG PS 0–2, and the majority (96%) had undergone prior nephrectomy. Patients were assessed for activity every three months (mos.) by CT. The primary endpoints were response rate (RR) evaluated by RECIST criteria and time to progression (TTP). Results: To date, 20 pts are evaluable for response: of them, 13 (59%) achieved a partial response (PR) after 3 mos. of therapy whose median duration was 13 mos. (range, 7–18), while 7 (31%) remained with stable disease (SD) with a median length of 14 mos. (range, 5–17). No complete responses have been observed. Among those who progressed (2 pts), the median time to disease progression was 7 mos. At a median length of time of 15 mos., 18 pts. are continuing the therapy with SOR and in all of them the benefit achieved remained unchanged. Two pts discontinued the treatment because of the onset of side effects, while in 4 pts dose reductions were required. Grade 3/4 toxicities were: hypertension in 3 pts (13%), hand-foot skin reactions in 5 (22%), rash/desquamation in 4 (18%), diarrhoea in 2 (9%), fatigue in 6 (27%), bleeding in 2 (9%). Conclusions: These data confirm other experiences showing the efficacy of SOR in previously treated patients with mRCC. However, notwithstanding the rather small sample size of pts., the overall clinical benefit rate (PR+SD) turned out particularly high (&gt; 90%): chiefly, the evidence of a long lasting disease control both for patients achieving partial response and for those with stable disease makes SOR a very useful treatment for patients with mRCC. No significant financial relationships to disclose.
Effects of anti-TGF-β1–3 antibodies on toxicities of whole thorax irradiation
Authors: N. C. Choi, S. D. Park, P. Biggs, M. Hawes, S. Ledbetter, L. Gerweck
Journal: Journal of Clinical Oncology (2008)

22083 Background: Smad 3 (intracellular signaling molecule associated with TGF-β) null mice shows very limited inflammation and fibrosis after whole thoracic irradiation. The goals of this study were to measure protective effects of anti-TGF-β1–3 antibodies against toxicities of whole thorax irradiation. Methods: Fibrosis prone C57BL/6 mice (n=126) were randomly allocated into: (a) test and (b) control groups, with each group consisting of 5 cohorts for 5 different levels of single radiation dose ranging from 0 Gy (n=5), 10 Gy (n=10), 13 Gy (n=18), 16 Gy (n=13), and to 19 Gy (n=13). The test group (Tab) was given anti-TGF-β1–3 antibodies, intraperitoneal (IP) injection at 1 mg/Kg Monday, Wednesday, and Friday of Weeks (wks) 1, 2, 3 & 4, and 20, 21, 22 & 23. The control group (Cab) was given non-immune antibodies. The radiation dose was given in a single fraction. Statistical methods included Kaplan-Meier product-limit method for survival, the log-rank test for the differences in the survival curves, and standard log-logit dose response relationship for determination of radiation dose resulting in 50% mortality (LD50) at day-240. Results: Multifocal chronic alveolitis was observed in 0% vs. 80% for 13 Gy/Tab vs. 13 Gy/Cab respectively. This pathologic change was present in most animals from the 19 Gy and absent in either the 0 Gy/Cab or 0 Gy/Tab groups. The LD50s at days 180, 210, and 240 were 16 Gy, 13.9 Gy, and 13.2 Gy (12.7–13.7) for the Cab compared with 15.9 GY, 14.2 Gy, and 13.6 Gy (12.4–15.9) for the Tab respectively (p=0.2). There is a trend for increased LD50 for the Tab at 13 Gy. The median survival times were 155 days and 175 days for the 19 and 16 Gy groups with no difference between the Cab and Tab (p = 0.2). However, at 13 Gy, survival rate was 38% for the Cab compared with 50% for the Tab. Conclusions: Anti-TGF-β1–3 antibodies seem to have protective effect against pneumonitis/fibrosis and death at the dose of 13 Gy and less. Further studies are warranted for determination of optimal timing and dose of anti-TGF-β1–3 antibodies for the maximum protective effect. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genzyme Corporation
A phase II study of oxaliplatin (OX), capecitabine (CAP), and bevacizumab (BV) in the treatment of metastatic colorectal cancer
Authors: J. C. Bendell, N. Fernando, M. Morse, G. Blobe, D. Yu, L. Sutton, S. Schaffer, W. Honeycutt, A. Franklin, H. Hurwitz
Journal: Journal of Clinical Oncology (2006)

3541 Background: BV, a monoclonal antibody against vascular endothelial growth factor, provides a survival advantage when added to first line therapy for metastatic colorectal cancer. CAP allows for fluoropyrimide treatment without the inconvenience of an infusion pump. We aimed to investigate the combination of OX, CAP, and BV (XeloxA) as a more convenient and active regimen. Methods: Pts with untreated metastatic colorectal cancer received OX 85 mg/m 2 d1, CAP 1000 mg/m 2 BID d1–5 and 8–12, and BV 10 mg/kg d1. Cycles were repeated every two weeks. The starting dose of CAP was changed to 850 mg/m 2 BID due to toxicity in the first 28 patients. Data were analyzed under an intention to treat method. Results: 50 pts received therapy (28M, 22F), median age 55 (range 24–81). Data were available on 49 pts. The most common toxicity was diarrhea, with 12/49 (24%) having grade 3 diarrhea, and 22% with grade 2. After the dose reduction of CAP, 3/21 (14%) pts had grade 3 diarrhea and 2/21 (10%) with grade 2 as compared to 32% grade 3 and 32% grade 2 at the higher dose. At the higher dose of CAP 4% of pts had grade 3 hand-foot syndrome (HFS) and 39% had grade 2. At the lower dose, 10% had grade 3 and 5% had grade 2. Other grade 3 toxicities were minimal, including neurotoxicity (8%), vomiting (6%), and neutropenia (4%). There were 23 responses, 1 CR and 22 PR (RR=47%; 95% CI: 33%-62%). 21 pts had stable disease (43%). Median progression free survival (PFS) was 10.7 months (95% CI: 8.6–13.6). Conclusions: XeloxA is a well tolerated, active regimen in the first line treatment of metastatic colorectal cancer. RR and PFS data approximate that of infusional 5-FU regimens in combination with BV without the necessity of an infusion pump. [Table: see text]
Phase II study of CKD602, a camptothecin analog, in combination with carboplatin for the treatment of recurrent ovarian cancer
Authors: C. Choi, Y. Lee, C. Kim, H. Kang, T. Kim, J. Lee, J. Lee, D. Bae, B. Kim
Journal: Journal of Clinical Oncology (2009)

5554 Background: Belotecan (Camtobell, Chong Keun Dang Corp, Seoul, Korea; CKD602) is a camptothecin derivative with anti-tumor properties recently developed. This phase II study was designed to evaluate the toxicity and efficacy of belotecan combined with carboplatin in patients with recurrent epithelial ovarian cancer (EOC). Methods: Belotecan 0.3 mg/m 2 /day (days 1–5) and carboplatin AUC 5 (day 5) were administered every 3 weeks for 6 cycles. Eligible patients had recurrent EOC, peritoneal serous cancer, or fallopian tube cancer. The primary objective was to determine response rate defined by Response Evaluation Criteria in Solid Tumors and CA-125 response; other end points included toxicities and progression free survival (PFS). Results: Until this preliminary analysis, sixteen patients had received the treatment and 13 patients were evaluable for response. Eight patients had platinum-sensitive disease (minimum treatment free interval≥6 months) and 6 had platinum-resistant disease (minimum treatment free interval &lt;6 months). Overall response rate was 53.9%; there were 3 complete responses (23.1%), 4 partial responses (30.8%), 4 patients with stable disease (30.8%), and two patients with progressive disease (15.4%). Grade 3 and 4 hematologic toxicities included neutropenia (38%), thrombocytopenia (25%), and anemia (15%); there was one episode of febrile neutropenia. None of the patients experienced grades 3 and 4 gastrointestinal toxicities, including nausea, vomiting, and anorexia. Conclusions: The newly developed topoisomerase I inhibitor, belotecan (CKD-602), combined with carboplatin is a well-tolerated regimen with activity in recurrent EOC; further testing of this regimen is warranted. No significant financial relationships to disclose.
PKLR promotes colorectal cancer liver colonization through induction of glutathione synthesis
Authors: Alexander Nguyen, Jia Min Loo, Rohit Mital, Ethan M. Weinberg, Fung Ying Man, Zhaoshi Zeng, Philip B. Paty, Leonard Saltz, Yelena Y. Janjigian, Elisa de Stanchina, Sohail F. Tavazoie
Journal: Journal of Clinical Investigation (2016)

Colorectal cancer metastasis to the liver is a major cause of cancer-related death; however, the genes and pathways that govern this metastatic colonization event remain poorly characterized. Here, using a large-scale in vivo RNAi screen, we identified liver and red blood cell pyruvate kinase (PKLR) as a driver of metastatic liver colonization. PKLR expression was increased in liver metastases as well as in primary colorectal tumors of patients with metastatic disease. Evaluation of a murine liver colonization model revealed that PKLR promotes cell survival in the tumor core during conditions of high cell density and oxygen deprivation by increasing glutathione, the primary endogenous antioxidant. PKLR negatively regulated the glycolytic activity of PKM2, the major pyruvate kinase isoenzyme known to regulate cellular glutathione levels. Glutathione is critical for metastasis, and we determined that the rate-limiting enzyme of glutathione synthesis, GCLC, becomes overexpressed in patient liver metastases, promotes cell survival under hypoxic and cell-dense conditions, and mediates metastatic liver colonization. RNAi-mediated inhibition of glutathione synthesis impaired survival of multiple colon cancer cell lines, and pharmacological targeting of this metabolic pathway reduced colonization in a primary patient-derived xenograft model. Our findings highlight the impact of metabolic reprogramming within the niche as metastases progress and suggest clinical potential for targeting this pathway in colorectal cancer.
Prospective Evaluation Of Allo-HSCT From Haploidentical-Related Donors Compared With Matched Sibling Donors and Unrelated Donors For Patients With Hematological Malignancies: Results From An Open-Label Trial
Authors: Yi Luo, Haowen Xiao, Xiaoyu Lai, Jimin Shi, Yamin Tan, Jingsong He, Wanzhuo Xie, Weiyan Zheng, Yuanyuan Zhu, Xiujin Ye, Zhen Cai, Maofang Lin, He Huang
Journal: Blood (2013)
Placebo and nocebo effects in randomized double-blind clinical trials for fatigue in advanced cancer patients
Authors: M. de la Cruz, D. Hui, H. A. Parsons, P. Lynn, C. Parker, D. Urbauer, E. Bruera
Journal: Journal of Clinical Oncology (2009)

9640 Background: We have previously reported significant placebo response in randomized controlled treatment trials for cancer related fatigue (CRF). We conducted a retrospective study to determine the frequency and predictors of response to placebo and nocebo effect in patients with CRF. Methods: We reviewed patients that received placebo in two previous randomized clinical trials conducted by our group and determined the proportion of patients who demonstrated clinical response to fatigue using an increase (ΔFACIT-F score) &gt; 7 from baseline to day 8, and those with nocebo response as those who reported side effects. Baseline patient characteristics and symptoms recorded from the Edmonton Symptom Assessment Scale (ESAS) were analyzed to determine their association with placebo and nocebo effects. Results: A total of 105 advanced cancer patients received placebo. 59 (56%) patients responded to placebo (median Δ FACIT-F score of 22). Worse baseline anxiety and well-being subscale score (univariate) and well-being (multivariate, MR) were significantly associated with placebo response. Common side effects reported were insomnia (79%), anorexia (53%), nausea (38%) and restlessness (34%). MR analysis showed that worse baseline (ESAS) sleep, appetite, nausea, and restless are associated with increased reporting of these side effects ( Table ). Conclusions: Nearly half of advanced cancer patients enrolled in the fatigue trials responded to placebo. Worse physical well-being score was associated with placebo response. Patients experiencing specific symptoms at baseline were more likely to report these as side effects of the medication. These findings should be considered in fatigue clinical trial design. [Table: see text] No significant financial relationships to disclose.
Geographic variation in surveillance strategies following surgery for upper aerodigestive tract cancer
Authors: M. H. Johnson, F. E. Johnson, R. C. Paniello, K. S. Virgo
Journal: Journal of Clinical Oncology (2004)

5585 Background: The optimal method of follow-up for patients with upper aerodigestive tract carcinoma (UADT) after curative-intent primary treatment is unknown. There is evidence that the intensity of surveillance varies substantially among clinicians. Analysis of geographic variation in utilization of medical resources is often used to identify regions of over- or under-utilization. Methods: We surveyed the membership of the American Head and Neck Society regarding their recommended frequency of office visits and 13 surveillance tests (chest x-ray, head-neck CT, chest CT, head-neck MRI, head-neck sonogram, bone scan, CBC, liver function tests, thyroid function tests, serum electrolyte levels, tumor markers, esophagoscopy, and bronchoscopy) for their patients after potentially curative therapy for UADT cancers. Results: Of the 1,322 members surveyed, 610 (46%) responded, of which 420 (32%) were evaluable. Pooled responses from nine U.S. census regions, 12 metropolitan statistical areas (MSAs), and overseas members (16% of evaluable responses) were compared. There were statistically significant variations in practice patterns among census regions for office visits, CBC, head-neck CT, sonography, and esophagoscopy (p<0.05, ANOVA). The mean frequency of office visits also differed significantly (p<0.05) among MSAs, ranging from six in Houston to nine elsewhere during year 1 for patients with stage I lesions. Non-U.S. members use significantly more blood tests, imaging studies, and endoscopy for routine cancer surveillance than U.S. members (p<0.05). Surprisingly, the penetration rate of managed care organizations had no significant effect on post-treatment surveillance intensity. Conclusions: This analysis indicates that only a small portion of the wide variation in observed follow-up practice patterns can be explained by geographic determinants. No significant financial relationships to disclose.
High-resolution electrocardiography (HRECG) in detection of preclinical cardiotoxicity of sunitinib and sorafenib in renal cell carcinoma (RCC) patients
Authors: J. Mardiak, M. Mego, D. Urbanova, B. Mladosievicova, J. Postulka, Z. Sycova-Mila, J. Obertova, K. Rejlekova, T. Salek
Journal: Journal of Clinical Oncology (2008)

16097 Background: Tyrosine-kinase inhibitors (TKI), have significant clinical activity in patients (pts) with RCC. Cardiotoxicity is relatively common toxicity of these molecules. Schmidinger et al (ASCO, 2007) have detected preclinical and clinical stage of myocardial damage in more than 20% of patients treated with TKIs. ECG-changes and biochemical markers are the most important indicators of this damage. HRECG is promising method for early identification of patients at risk of anthracycline cardiotoxicity. The aim of this prospective observational study was to investigate the value of HRECG in combination with biochemical markers in identification myocardial damage in preclinical stage in pts undergoing TKI-treatment for RCC. Methods: Eighteen consecutive patients (5F/13M; median age 63, range 47–75) intended for TKI treatment were analyzed for medical history of coronary artery disease (CAD) and risk-factors. Time- and frequency-domain analyses of HRECG, biochemical markers of cardiac damage (cardiac troponin T -cTNT, pro brain natriuretic peptide- proBNP-) and echocardiography were performed before and 12 weeks after begining of treatment. Results: Twelve patients were treated with sunitinib and 6 patients with sorafenib. All patients had normal pro-BNP and TNT at baseline. Median follow-up was 6 months (range: 3–8 months). During this period, we didn´t observed clinical or laboratory signs of myocardial damage. Mean values of proBNP and cTNT were 401 pg/ mL and 0.01 ng/mL before therapy and 406 pg/mL and 0.01 ng/mL after 12 weeks of therapy (p = 0.96). The HRECG had not shown any signs of myocardial damage. Conclusions: In presented study the number of events of myocardial damage was lower than was expected. However, based on our results, it seems that normal HRECG before and after 12 weeks of therapy could be a usefull marker for selection of patients with low risk of cardiotoxicity induced by sunitinib and sorafenib. Longer follow-up is needed. Updated clinical results will be presented. No significant financial relationships to disclose.