tbuckley/cabot-search huggingface dataset:
Hepatic artery infusion (HAI) of oxaliplatin (Ox) as third and fourth-line therapy for patients with hepatic metastases (M) from colorectal cancer (CRC) pretreated with systemic Ox
Authors: H. Gollasch, B. Gebauer, I. Sturm, P. Thuss-Patience, D. Pink, C. Stroszczynski, A. Kretzschmar
Journal: Journal of Clinical Oncology (2004)

3695 Background: The liver is the predominant site of M from CRC. HAI of cytotoxic agents has a long tradition but due to technical complications and lack of a survival benefit compared to systemic treatment it did not become widely accepted as 1st-line treatment of patients (pts) with M from CRC confined to the liver. HAI might serve as a salvage option for pts in whom all available systemic therapies failed and in whom liver M are still dominant. Methods: We retrospectively analysed the outcome of all pts who were treated with HAI of Ox after systemic pretreatment with Ox in our institution. Results: All 10 pts (age 35–68) had received fluoropyrimidines, irinotecan and Ox in two (5 pts) or three previous palliative lines and were pretreated with liver resection (1) and local thermoablation (3). In 8 cases disease progressed while systemic Ox was given. 2 pts had small lung M beside advanced liver M; CEA median 67 (3 - 2511). HAI was introduced in median 14 months (8 - 31) from start of first line palliative therapy. Ox 100 mg/m2 (9 pts) and 130 (1) was infused over 2 h via interventionally placed inguinal port (2) or via repeated single-use catheters (8) (tip in the proper hepatic artery) and accompanied by i.v. 5-FU (FA-modulation/bolus/infusion; mg/m2 :400–400-2400/48 h)in 8 pts or oral capecitabine (2.5 g/m2 d1–14)in 2. In median 6 cycles (2–9), q 2–3 weeks, were applied in an outpatient setting. Toxicity was mild beside one port-infection, one case of prolonged but uncomplicated neutropenia IV° and repeated severe but reversible abdominal pain during HAI in 2 cases. No neurosensory toxicity was seen. Beside 3 PR we observed one MR accompanied by CEA and CA 19–9 drop of 94 % and 98 % resp. 4 pts had SD while in 2 pts disease in the liver progressed. Extrahepatic progression occured in 5 pts while they received HAI. Median TTP, TTP in the liver and survival from start of HAI were 4 (1–8), 6 (1–8) and 13 (2 - 15+) months. Conclusions: HAI of Ox via interventionally placed catheters in combination with systemic fluoropyrimidines is a feasible and effective outpatient option for heavily pretreated pts with hepatic M from CRC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Synthelabo, Germany
Retrospective analysis: Patients with ovarian cancer at National Cancer Institute of Mexico
Authors: F. Morales-Vasquez, D. Gallardo, L. Tirado, H. N. López-Basave, D. Cantú, C. Mendez
Journal: Journal of Clinical Oncology (2009)

e16573 Background: Ephitelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies among women worldwide. Little is known about reproductive factors or lifestyle determinants and ovarian cancer prognosis. The purpose of this study was to analyze the pathologic, clinical and other characteristics. Methods: This study included all EOC seen at the Institute from 2000–2006. Epidemiological and clinical variables were collected from the patients’ medical records. Exposure data on prediagnostic factors were collected through questionnaires. The cases were followed-up until December 31, 2007. Cox proportional hazard regression model was used to estimate the prognostic effect of each factor in terms of hazard ratios (HR) and 95% confidence intervals (CI), following adjustment for age at diagnosis, FIGO tumor stage and WHO grade of tumor differentiation. Results: 571 cases of ovarian cancers. Median age was 51 years, (range 18–95). 20.30%, 4.4%, and 63.5% of patients had stage I, II and III, respectively. The histological types: 52.2% serous, 17.2% endometrioid, 12.8% of mucinous origin; 62.5% underwent radical surgery, 24% with optimal cytorreduction. The mean follow-up was 60 ± 22 months. The overall three-year survival was 97.4% and 98% for mucinous and serous tumors, respectively. The survival rate was 100%, 90%, and 71.8% in stages I, II and III, respectively. After adjustment for the tumor characteristics, no clear associations were detected between reproductive history, anthropometric characteristics, factors before diagnosis (alcohol consumption, smoking and physical activity over lifetime), nor family history of breast cancer or ovarian cancer and survival Conclusions: Our findings indicate that the tumor characteristics significantly influenced the risk of death from ovarian cancer and no clear associations were detected between others factors and the survival. In this cohort the median age for ovarian cancer were 51 years old, one decade before than other reports. No significant financial relationships to disclose.
A phase 1/2 study of STA-4783 in combination with paclitaxel and carboplatin in chemo-naïve advanced non-small cell lung cancer (NSCLC)
Authors: M. Jacobs, R. Weber, J. Hainsworth, L. Schwartzberg, J. Strauss, N. Tatsuta, Z. Du, M. McLeod, T. Dahl, R. Salgia
Journal: Journal of Clinical Oncology (2005)

7106 Background: STA-4783 (S) is a bis-thiobenzoylhydrazide that induces heat shock protein 70 (hsp 70). S significantly enhanced the antitumor activity of paclitaxel (P) in xenograft models, where single agent S had no activity. P with S given IV over 3 hours q 3 weeks was studied in a Phase 1 trial (ASCO 2004 Abstract 3124). Treatment was well-tolerated and maximum tolerated dose (MTD) was not reached. A Phase 1/2 trial was initiated in chemo naïve patients with advanced NSCLC. Methods: Phase 1 (safety/PK/MTD) was followed by a Phase 2 randomized two-arm portion. Two dose levels were evaluated in Phase 1: Cohort 1 carboplatin (C) AUC 6, P 175 mg/m2, and S 233 mg/m2; and if MTD was not observed, Cohort 2 was enrolled with the C AUC 6, P 200 mg/m2, and S 266 mg/m2. Dosing was IV q 3 weeks for up to 6 cycles in the absence of dose limiting toxicity or progression. In the Phase 2 portion 86 patients are planned to be randomized 1:1 to C AUC 6 + P 200 mg/m2 q 3 weeks or the CPS dose selected in Phase 1. The Phase 2 primary endpoint is time to progression, with secondary endpoints of response rate, survival, and quality of life. Study pharmacodynamic parameters include natural killer (NK) cell activity and hsp70 level. Results: Sixteen patients were treated in Phase 1, 7 in cohort 1 and 9 in cohort 2. No first cycle dose-limiting toxicities were seen in either cohort. Phase 1 AEs included (usually Grade 1–2) arthralgia and myalgia, peripheral neuropathy, rash, nausea and vomiting, fatigue, alopecia, edema, dehydration, constipation, and decreased blood counts. Eleven patients completed 6 cycles of therapy. Eight patients (50%) achieved a partial response (PR). Seven of the 8 patients with evaluable samples showed increased NK cell activity. Given the safety profile of cohort 2, this CPS dose level was used in Phase 2. As of submission, seventy patients have been randomized to Phase 2. Conclusions: CPS is well-tolerated at the dose levels studied, and the overall safety profile of CPS appears similar to that of CP alone. CPS has shown encouraging clinical activity, and the correlative NK activity data suggest that S is biologically active in vivo. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Synta Synta Synta
The JAK Inhibitor INCB20 Induces Antiproliferative and Apoptotic Effects in Human Myeloma Cells In Vitro and In Vivo.
Authors: Renate Burger, Steven Legouill, Yu-Tzu Tai, Reshma Shringarpure, Klaus Podar, Laurence Catley, Pierfrancesco Tassone, Paola Neri, Teru Hideshima, Dharminder Chauhan, Eian Caulder, Kris Vaddi, Claire L. Neilan, Martin Gramatzki, Jordan S. Fridman, Kenneth C. Anderson
Journal: Blood (2005)
Use of alternate splicing to identify subgroups in uniformly treated newly-diagnosed myeloma
Authors: N. C. Munshi, C. Li, S. Minvielle, P. Moreau, S. B. Amin, M. Magrangeas, K. C. Anderson, H. Avetloiseau
Journal: Journal of Clinical Oncology (2009)

8602 Gene function is modulated at multiple levels. Besides expression level changes, post-transcriptional changes such as alternate splicing alter specificity of gene function. Misregulation of alternate splicing is associated with various disease processes including cancer. We have analyzed alternate splicing in myeloma (MM) using high throughput exon array analysis. Affymetrix Human Exon 1.0 ST Arrays used in this investigation, besides expression levels, also provides information on presence of each exon and identifies recurrent alternately spliced genes. We evaluated 170 newly-diagnosed patients with MM treated homogeneously in tandem transplantation IFM trials using CD138 purified MM cells. Xray array tool (Biotique systems) and dChip software was modified to analyze exon array data. We first normalized gene-level expression values across samples, and then identified differentially expressed exons to identify alternate splicing events. We observed over 100 genes with alternate splicing in myeloma with frequency in more than 20% patients. Unsupervised hierarchical clustering showed two groups within myeloma patients which differ in overall survival (OS). Dividing the group based on response, 52 alternately spliced exons were identified as influencing response to therapy including CD79A exon 4, XRCC exon 3 and 17, PRKDC exon 4, NIT 2 exon 4, Calmin exon2, MADH1 exon 7, TBX5 exon 2, Amyloid beta exon 14 with the highest frequency of alternate splicing. Amongst these, 32 genes had the most influence on response with over 50% differential frequency in patients achieving CR. Similarly 85 alternately spliced genes are influencing OS between groups at 48 month survival cut-off. 49 genes within this group had the most influence on OS. Shared spliced variants between both response and survival groups suggesting their biological and functional significance. Further validation of these alternate splicing is under investigations. This study highlights that alternate splicing is observed with significant frequency and demand need for evaluation of not only the expression level of genes but also post translational modifications. The spliced genes identified here are important target for therapy as well as possible immune modulation. No significant financial relationships to disclose.
Differential gene expression in preoperative study of selenium and vitamin E chemoprevention in prostate cancer
Authors: J. Kim, D. Tsavachidou, K. Do, S. Wen, R. Babaian, L. Pisters, C. Pettaway, P. Troncoso, C. Logothetis, T. McDonnell
Journal: Journal of Clinical Oncology (2007)

1523 Background: To identify genes that distinguish between treatments, tumor types, and their interaction, we undertook a microarray analysis of tissue in a preoperative chemoprevention study of L-selenomethionine (SeMet) and vitamin E (VE) in prostate cancer. Methods: Forty-eight men with prostate cancer were enrolled in a single-institution, double-blind, placebo-controlled trial that randomized patients into four groups receiving 200 μg SeMet, 400 IU VE, a combination of the two, or placebo (see 2006 ASCO abstract 1007). All patients also received a multivitamin and vitamin C (250 mg) daily. Modeled on the Selenium and Vitamin E Cancer Prevention Trial, this study included patients scheduled for prostatectomy within 3 to 6 wk of registration who had a prostate-specific antigen level &lt;10 ng/mL within 3 mo of registration, clinical stage T1c/T2 disease, and a Gleason score =7. From core biopsy specimens, we isolated cancerous and noncancerous cells, tumor-adjacent stroma, and non-tumor adjacent stroma of 38 evaluable radical prostatectomy specimens using laser capture microdissection. The cDNA hybridized to oligonucleotide microarrays was generated from extracted RNA, which had undergone two rounds of linear amplification. Expression levels were extracted using the positional-dependent nearest-neighbor model, and after ANOVA model analysis, effects were contrasted using the approximate z-test with statistic z. The beta-uniform mixture model was used to analyze p values and control the false discovery rate. Ingenuity Pathway Analysis followed. Results: Differentially expressed genes were selected that were common in the combination and selenium arms or in the combination and VE arms: unique in tumor-69 in combination and selenium, 71 in combination and VE; unique in stroma-64 in combination and selenium, 45 in combination and VE; unique in normal tissue-48 in combination and selenium, 38 in combination and VE. Conclusions: This work demonstrates that gene expression may be correlated with specific therapeutic interventions, and this analysis indicates that dietary antioxidants modulate gene expression in human prostate cancer cells and pathways relevant to prostate carcinogenesis. No significant financial relationships to disclose.
Thrombocytosis as a prognostic factor for survival in patients with metastatic renal cell carcinoma
Authors: S. A. Misbah, P. E. Shaheen, P. J. Elson, S. Negrier, R. J. Motzer, S. W. Andresen, R. M. Bukowski
Journal: Journal of Clinical Oncology (2005)

4599 Background: It has been suggested that thrombocytosis, defined as a platelet count >400 K/uL, is a negative predictor for survival in patients with metastatic renal cell carcinoma (mRCC), (Symbas, BJU Int 2000), however, this is not a uniform finding, (Negrier, Ann Oncol 2002, Inoue, Int J Urol 2004). Methods: To address this issue a retrospective analysis of 700 previously untreated patients (pts) entered onto institution review board approved phase I, II, or III clinical trials conducted in the United States and Europe between 1982 and 2002 was conducted. Results: 71% of pts were male, median age at on-study was 57.9 years, 77% of pts had prior nephrectomy, and 19% had prior radiotherapy (RT). 21% of pts were ECOG performance status (PS) 0, 64% were PS 1, and 15% were PS 2. Median baseline platelet count was 304 K/uL, range, 86–1420. Thrombocytosis was present at study entry in 25% of pts. 87% of pts have died; median survival was 13.0 months. In univariable analysis, patients with elevated platelet counts had significantly shorter survival than patients with normal platelet counts; median survivals of 14.6 and 8.4 months, respectively, logrank p<.001. Platelet count, however was associated with a number of clinical and biochemical factors, including gender, age, PS, time from diagnosis (dx) to study entry, RT, liver metastasis, number of metastatic sites, hemoglobin, WBC, and serum alkaline phosphatase (Spearman correlation or Wilcoxon rank sum p<.05). Several of these factors, in addition to others have previously been reported to be prognostic for survival in this population, and therefore multivariable analyses (Cox proportional hazards models) were conducted to determine if thrombocytosis is an independent predictor. Adjusting for gender, age (≤60 vs >60), PS, time from dx (≥1 vs <1 year), RT, number of metastatic sites (1 vs >1), hemoglobin (normal vs below laboratory’s lower limit of normal), WBC (≤11.0 vs >11.0 K/uL), serum lactate dehydrogenase (≤1.5 vs >1.5 X laboratory’s upper limit of normal) and alkaline phosphatase (≤100 vs >100 U/L), thrombocytosis was still seen to impact negatively on survival, p<.001. Conclusions: Thrombocytosis is an independent prognostic factor for survival in pts with mRCC. No significant financial relationships to disclose.
Predictive value of skin toxicity severity for response to panitumumab in patients with metastatic colorectal cancer (mCRC): A pooled analysis of five clinical trials
Authors: J. Berlin, E. Van Cutsem, M. Peeters, J. R. Hecht, R. Ruiz, M. Wolf, R. G. Amado, N. J. Meropol
Journal: Journal of Clinical Oncology (2007)

4134 Background: Panitumumab, a fully human monoclonal antibody against the epidermal growth factor receptor (EGFr), is approved for EGFr-expressing mCRC patients (pts) with disease progression (PD) on or following fluoropyrimidine (5FU)-, oxaliplatin (Ox)-, and irinotecan (Ir)-containing chemotherapy. Skin toxicities are common with panitumumab; we examined the association between severity of skin toxicity and panitumumab efficacy. Methods: Data from 5 clinical trials were pooled (4 phase II studies and 1 phase III study). Pts with mCRC had documented PD on or after 5FU, Ox, and/or Ir. Pts received panitumumab 6 mg/kg every two weeks (Q2W) or 2.5 mg/kg weekly (QW) until PD or intolerability. Tumors were assessed using modified WHO or RECIST criteria (blinded central review in 4/5 studies). Endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). PFS and OS were measured from enrollment. Only pts with =2 infusions (exposure over 2 wks for QW dosing or over 4 weeks for Q2W dosing) were analyzed to help correct for lead-time bias. Results: 612 of 640 pts were included in the analysis set (62% were male, 92% were white, and median age [range] was 61 [21, 88] years). The median (95% CI) duration of PFS was 8.4 weeks (8.0 to 11.3), the median (95% CI) survival was 6.9 months (6.2 to 7.9), and the ORR (95% CI) was 9.0% (6.8 to 11.5). The most common skin toxicities (any grade, grade 3/4) were erythema (54%, 4%) pruritus (53%, 2%), dermatitis acneiform (52%, 5%), and rash (39%, 2%). ORR, PFS, and OS appeared to favor pts with grade 2–4 skin toxicity vs pts with grade 0- 1 skin toxicity ( table ). Conclusion: In this large combined analysis, severity of skin rash was correlated with increased efficacy of panitumumab in terms of ORR, PFS, and OS. [Table: see text] No significant financial relationships to disclose.
Monitoring bortezomib therapy in multiple myeloma: Screening of cyclin D1 overexpression as a potential prognostic marker for response to treatment
Authors: T. B. Ngo, J. Felthaus, G. Ihorst, M. Engelhardt, R. Wäsch
Journal: Journal of Clinical Oncology (2008)

8614 Background: Cyclin D1 (CCND1), 2 (CCND2) and 3 (CCND3) are overexpressed in almost all MM and their deregulation has prognostic value. As cyclins are substrates of the proteasome, proteasome inhibition by bortezomib may stabilize the cell cycle and facilitate the induction of apoptosis, as it has been recently shown for breast cancer (Ishii et al, J Nat Canc Inst 2006). Methods: In a clinical approach, our objective was to define the expression levels of D-type cyclins in MM pts treated with bortezomib at our medical center between 1/2003 and 3/2006, aiming to define cyclins D as prognostic markers for monitoring treatment efficacy. We analyzed CCND1, CCND2 and CCND3 by real-time PCR in bone marrow specimens of 20 pts and correlated the expression with clinical features and other prognostic markers such as BM infiltration (BMI), ß2-microglobulin (ß2-MG) levels, 13q14 status and light chain-secretion. Results: The median number of bortezomib cycles in all pts was three and the best response to therapy was CR in one, PR in 11, SD in five and PD in 3/20. All pts who responded to bortezomib showed overexpression (OE) of CCND1. Pts not responding to bortezomib had very low or negative CCND1 cDNA levels. By 3/2007, 50% of all pts in CR, PR or SD had eventually relapsed. Of those pts, three relapsed, despite CCND1 OE prior to therapy. Six pts (66%) with CCND1 OE remained in response. Four pts displaying very high cyclin D1 expression levels were in either PR or SD, even after a follow-up of up to six years. Pts with CCND2 and CCND3 OE responded to bortezomib, but showed a relatively higher relapse rate (50% and 75% respectively). The amplification of the cyclin D genes was not found to correlate with BMI, ß2-MG, light chain secretion or del 13q14. The risk for progression after bortezomib treatment was significantly decreased in pts with cyclin D1 OE (HR 0.102, 95%CI 0.021–0.498, p=0.0048). Consequently, the progression free survival was significantly prolonged with cyclin D1 OE compared to those pts with low or negative cyclin D1 cDNA levels (p=0.0011). Conclusions: Our findings raise the possibility that CCND1 is a specific marker for predicting a lasting response after bortezomib treatment in MM, warranting a prospective study with a larger patient cohort. No significant financial relationships to disclose.
Beware of the “Bronchocele,” Particularly in Patients with a History or Risk Factors for a Mucinous Carcinoma: A Response to the Article “Resection of a Solitary Pulmonary Metastasis from Prostatic Adenocarcinoma Misdiagnosed as a Bronchocele: Usefulness of 18F-Choline and 18F-FDG PET/CT” by Calais et al.
Authors: Haval Balata, Matthew Evison, Paul O’Donnell
Journal: Journal of Thoracic Oncology (2015)
A phase II study of bavituximab and sorafenib in advanced hepatocellular carcinoma (HCC).
Authors: Adam Charles Yopp, Amit G Singal, Yull Edwin Arriaga, Udit N. Verma, Joseph Shan, Nikoletta Kallinteris, Muhammad Shaalan Beg, John C. Mansour, Hao Zhu
Journal: Journal of Clinical Oncology (2015)

345 Background: Bavituximab a first-in-class immunomodulator targeting phosphatidylserine (PS), a lipid externalized on tumor and endothelial cells. Preclinical and phase I studies demonstrated that sorafenib upregulates PS externalization and can be given safely with bavituximab. We evaluated the safety and clinical activity of bavituximab plus sorafenib in HCC. Methods: Patients with advanced HCC deemed ineligible for curative therapy with no previous systemic treament, ECOG score ≤ 2, Child Pugh score A or B7 received bavituximab, 3 mg/kg IV weekly, and sorafenib, 400 mg PO BID until disease progression or intolerable toxicity. 38 patients were accrued providing a power of 80% and two-sided significance level of 10% to show an 8.2 month time to progression compared to historical control, 5.5 months. Secondary endpoints included safety and tolerability, 4-month progression free survival, overall survival, and response rates. Correlative studies using pre- and post-treatment tumor biopsies included IHC analysis of regulatory, cytotoxic, and helper T cells in addition to macrophage infiltrates. Results: 38 patients were accrued, 7 still on treatment. Patient characteristics: median age: 60.5 years, male 74%, HCV: 79%, Black: 47%/Hispanic: 29%/White: 21%, previous treatment 37%, and metastases: 24%. Median follow-up is currently 6.1 months with current median TTP of 6.8 months (95% CI 3,10). Four month PFS is 76% and there are no partial or complete responses. Treatment related adverse events were observed in 53% of patients, one grade 3 (GI bleed), four grade 2 (DVT, anorexia, diarrhea, and infusion reaction). Most common grade 1 events were diarrhea (18%), fatigue (16%), and anorexia (16%). Six patients had tissue analyzed pre- and post-treatment, 2 of 6 demonstrated increase tumor infiltration of CD4+, CD8+, and macrophages with a corresponding decrease in Tregs. Conclusions: Bavituximab and sorafenib were well tolerated in patients with advanced HCC. When compared with historical controls, combination therapy demonstrated an improvement in TTP and PFS at four months. Combination therapy increases immune tumor infiltrates. Clinical trial information: NCT01264705.