tbuckley/cabot-search huggingface dataset:
Family history, race, and prostate cancer.
Authors: Joshua Schiff, Elisa M. Ledet, Emma M. Ernst, Cathryn E. Garvey, Patrick Cotogno, Oliver Sartor
Journal: Journal of Clinical Oncology (2017)

225 Background: African American (AA) race and family history (FH) of prostate cancer (PCa) increase the incidence and mortality of PCa. The goal of this study was to assess and compare FH in AA and Caucasian (C) men. Methods: During June 2015 through September 2016, 338 men with prostate cancer had FH collected at Tulane Cancer Center (C = 266 and AA = 72). A FH was defined as ≥ 1 1st degree relative with PCa and/or ≥ 2 affected 2 nd /3 rd degree relatives. Documented clinical factors were age at diagnosis (dx), Gleason score, incidence of radical prostatectomy (RP), and presence of metastases (at any time). Chi-square and Mann-Whitney U tests were performed to identify potential clinical correlates with regard to FH and race. Results: For demographics see table below. On average, men with a FH of PCa (n = 110) had a median age at dx of 59.6 as compared to those without a FH of PCa (n = 151) (median age at dx = 63.0). Overall FH patients (pts) were younger at dx (p = 0.00046). FH had a particularly impactful influence upon the age at dx for C men (p = 0.00086, 58 [n = 88] vs. 62.5 [n = 112]); statistics were limited for AA men. Gleason scores were not different between pts with or without a FH, and there was no relationship between Gleason score and race. Metastatic disease (mets) was detected in 23.97% of men (n = 93). C men with a FH of PCa (n = 40) were 1.55 times more likely to develop mets (p = 0.0352). AA data were limited so no comment can be made. No relationship was detected between the pts having undergone a RP and race, but pts with a FH of PCa (n = 61) were 1.39 times more likely to have undergone surgery (p = 0.016). Data by racial subsets were too limited to be conclusive. Conclusions: The study highlighted the significant impact that FH of PCa has upon age at dx and presence of mets. More AA data are needed to be conclusive. [Table: see text]
The efficacy of first-line IRIS with or without bevacizumab in patients with metastatic colorectal cancer: Analysis of two phase II studies.
Authors: Satoshi Yuki, Hiraku Fukushima, Toraji Amano, Michio Nakamura, Mineo Kudo, Norikazu Sonoda, Miki Tateyama, Yasuyuki Kawamoto, Kazuteru Hatanaka, Susumu Sogabe, Takuto Miyagishima, Nobuaki Akakura, Takashi Kato, Tomofumi Takagi, Ichiro Iwanaga, Kencho Miyashita, Manabu Onodera, Soh Saitoh, Yuh Sakata, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2013)

e14604 Background: The safety and efficacy of first-line IRIS (S-1 in combination with irinotecan; Komatsu Y, et al. Oncology, 2011) and IRIS/Bev (IRIS in combination with bevacizumab (Bev); Komatsu Y, et al. Acta Oncol, 2012/Yuki S, et al. 2013 ASCO-GI) have been evaluated in patients with metastatic colorectal cancer (mCRC). This time, no randomized studies comparing these regimens have been performed. This retrospective analysis compared efficacy and safety data for the two regimens from separate phase II studies performed at Hokkaido Gastrointestinal Cancer Study Group (HGCSG). Methods: Patients with histologically confirmed unresectable metastatic or recurrent CRC and received no prior chemotherapy were enrolled. In the first trial, patients received irinotecan 100 mg/m 2 on day 1,15 and oral S-1 40 mg/m 2 twice daily on days 1-14 every 4 weeks (IRIS study: HGCSG0302). In the second trial, patients received the same regimen plus Bev 5 mg/kg on day 1,15 (IRIS/Bev study). Results: A total of 40 and 52 patients were enrolled the IRIS and IRIS/Bev studies, respectively. Patient characteristics were generally similar in both groups, whereas there were more cases of good performance status and less number of metastatic organ in IRIS/Bev group. The median overall survival was 39.6 months in IRIS/Bev, as compared with 23.4 months in IRIS, corresponding to a hazard ratio for death of 0.418 (p&lt;0.001). The median progression-free survival was 17.0 months in IRIS/Bev, as compared with 8.6 months in IRIS (hazard ratio for disease progression, 0.418; p&lt;0.001); the corresponding response rate were 63.5 percent and 52.5 percent (p=0.393).In a multivariate analysis of PFS and OS, IRIS/Bev (n=52) was significantly associated with longer PFS and OS compared with IRIS alone (n=40). Conclusions: In this retrospective comparison of two studies, the addition of Bev to IRIS appeared to improve outcome compared with IRIS alone in the first-line treatment of patients with mCRC.
Colorectal cancer patient utilization of an internet based clinical trials matching system
Authors: C. Bui, M. Hampshire, C. Vachani, J. Metz
Journal: Journal of Clinical Oncology (2006)

3624 Background: Colorectal cancer patients are increasingly looking to the Internet for information on clinical trials; however, services offering clinical trials recruitment have not been well defined. This study describes one of the first web-based cancer clinical trials matching resources and the demographics of the colorectal cancer patient user base. Methods: Oncolink ( http://www.oncolink.org ) is the web-based educational resource at the University of Pennsylvania and serves between 1.5–2 million pages per month to over 385,000 unique IP addresses. Oncolink, in conjunction with EmergingMed (New York, NY), launched one of the first clinical trials matching resources on the Internet. Patients input demographic and tumor-specific information via secure Internet-only registration or via the Internet with assistance from a call center, to match to trials. As of 12/2005, there were 112 total colorectal trials in the database. Results: Between 12/2000 and 9/2005 a total of 41,970 individual profiles were created, with 3289 (7.8%) by colorectal cancer patients. Other GI tumors accounted for 15% of profiles. Of the 3289 patients, 54% were male and 46% were female, and the median age was 55 (range 19–96). Most patients reported their disease as having spread to another organ (62%) or to lymph nodes (15.4%). Most patients were previously treated with surgery (81%), radiation (26%), chemotherapy (74%), and/or biological therapies (21%) (bevacizumab, cetuximab, interferon or interleukin). Patients who used the call center with the Internet were more likely to apply for enrollment in a clinical trial after review of the matches (77% vs. 10%, p&lt;0.001). The median number of trial matches in the system was 7 per patient. Of the 3289 colorectal patients, 681 patients (21%) went on to apply for enrollment to trials based on their matches. Conclusions: This report demonstrates that a significant percentage of colorectal cancer patients are willing to use the Internet to match to clinical trials. Contact with a call center greatly increases the likelihood of application to trials. Internet based clinical trials resources should maintain options for personal communication to increase the likelihood of enrollment to clinical trials. No significant financial relationships to disclose.
Does drug cost drive drug adherence? The designer drug phenomenon.
Authors: Jalal Ebrahim, Dolly Han, Sophie Hogeveen, Martina Trinkaus, Ehab Fadhel, Henrique Hon, Zahra Kassam, Geoffrey Liu, Christine E. Simmons
Journal: Journal of Clinical Oncology (2012)

6084 Background: Cancer patients (pts) are on many medications, both for malignancy and supportive therapies. The cost of oral medications are funded by either the pt, public, or private mechanisms. Low adherence rates are observed in oral treatments, and non-adherence is the primary cause of treatment failures. To our knowledge, cost-related adherence to oral therapy in the context of malignancy has not been studied extensively in the existing literature. We assessed the relationships between oral medication costs and adherence rates. Methods: This cohort study enrolled 453 pts at 3 outpatient heme/onc clinics in the Greater Toronto Area. A 7-item survey was designed to assess pt demographics, self-reported adherence to oral medication, type of drug coverage (private payer, public payer, self payer) and patients' perceived cost of oral drugs. Oral medications were recorded and actual monthly costs were calculated. Descriptive statistics were used to describe frequencies. Spearman Rank Order Correlations and Chi-Square Analyses were used to examine relationships between variables. Results: Of 453 pts, 50% had a private drug plan, 24% paid out of pocket, 44% had government funding and 4% reported their physician had arranged funding. 51% of pts had oral drug costs of ≥ $100/month. Self reported adherence to prescribed oral medications was 80%. As the cost of prescribed medications increased, so did self reported adherence (r=0.144, p=0.002). There was also a significant relationship between drug coverage and oral drug costs (c²=23.78, df=12, p=0.02). Pts paying out of pocket were significantly less likely than all other pts to have oral drug costs of ≥$500/month (11% vs 19%) Conclusions: As oral drug costs increase, so does likelihood of adhering to prescribed regimen. This implies that further pt education about the efficacy and importance of medications may help with adherence, regardless of cost. It is possible that pts are provided with more education regarding newer and more expensive agents than they are regarding older and cheaper agents, regardless of efficacy. Disparities observed in medication costs between those with private drug plans vs. those without suggests financial restrictions may affect prescription patterns in this group.
Mifepristone (MIFE), a glucocorticoid receptor (GR) antagonist, in combination with eribulin (E) in advanced solid tumors: A phase 1 study with dose expansion in patients (pts) with triple-negative breast cancer (TNBC).
Authors: Rita Nanda, Sharon Wilks, Manuel R. Modiano, Alexander I. Spira, Carlos Becerra, Jackie Walling, Dat Nguyen, Gabrielle Baker, Suzanne D. Conzen
Journal: Journal of Clinical Oncology (2015)

e12070 Background: GR expression is associated with a poor prognosis in estrogen receptor-negative (ER-) early stage breast cancer. Co-treatment with MIFE potentiates the effects of chemotherapy (ctx) in ER- breast cancer xenograft studies. Here we describe the results of a phase 1 dose-escalation study of MIFE+E, with an ongoing dose expansion cohort in pts with TNBC. Objectives: To determine the safety and tolerability of MIFE+E, the recommended phase 2 dose (RP2D) of MIFE+E, and to characterize pharmacokinetics (PK) and clinical activity of MIFE+E in pts with GR+ TNBC. Methods: Eligibility: relapsed/refractory advanced solid tumors; up to 5 prior ctx regimens for advanced disease; ECOG PS 0-1; and adequate end-organ function. Design: 3 + 3 dose escalation scheme. After a 7 day lead-in of oral daily MIFE alone, MIFE was continued daily and E was given on days 1 and 8 of a 21 day cycle. Results: To date, 13 pts with metastatic breast cancer (5 have TNBC) have been treated with MIFE+E: 7 GR+ tumors, 3 GR- tumors, and 3 with unknown GR status. Pts were treated at 3 dose levels (DL): 3 at DL1 [600 mg/d MIFE, 1.1 mg/m2 E]; 4 at DL-1a [300 mg/d MIFE, 1.4 mg/m2 E]; and 6 at DL-1 [300 mg/d MIFE, 1.1 mg/m2 E]. Two partial responses have been observed, both in pts with GR+ disease (1 with TNBC). Neutropenia leading to delay of E was dose limiting in 4 pts. Grade 3/4 neutropenia was observed in 9 pts, but was easily managed. Neuropathy was observed in 2 pts. No other significant toxicity was noted. The RP2D is 300mg/d MIFE and 1.1mg/m2 E. At this DL there were no dose-limiting toxicities, although 1 pt had grade 4 neutropenia in cycle 1, with brisk recovery of counts following growth factor. PK of MIFE and E were as predicted from published literature. Conclusions: MIFE+E is a novel combination designed to improve antitumor activity. It is well tolerated with evidence of clinical activity and no evidence of a drug-drug interaction between MIFE and E. RP2D is 300mg/d MIFE + E 1.1mg/m2. Study is ongoing in expansion phase where recruitment is limited to pts with GR+ TNBC. Clinical trial information: NCT02014337.
A phase II trial of olanzapine for the prevention of chemotherapy induced nausea and vomiting (CINV)
Authors: R. M. Navari, L. H. Einhorn, P. J. Loehrer, S. D. Passik, J. Vinson, M. L. Mayer, W. Pletcher, J. McClean
Journal: Journal of Clinical Oncology (2004)

8046 Background: In a previous Phase I study, olanzapine (Zyprexa) was demonstrated to be a safe and effective agent for the prevention of delayed emesis in chemotherapy naïve cancer patients receiving cyclophosphamide, doxorubicin, and/or cisplatin. Methods: Using the maximum tolerated dose of olanzapine in the Phase I trial, a Phase II trial was performed for the prevention of CINV in chemotherapy naive patients. The regimen was 5mg/day of oral olanzapine on the two days prior to chemotherapy, 10mg of olanzapine on the day of chemotherapy, day 1, (added to intravenous granisetron, 10 mcg/kg, and dexamethasone 20 mg) and 10 mg/day on days 2–4 after chemotherapy (added to dexamethasone, 8 mg p.o. BID, days 2,3, and 4 mg p.o. BID, day 4). Thirty patients (median age 58.5 yrs, range 25–84; 23 females; ECOG PS 0,1) consented to the protocol and all were evaluable. Results: Complete response (CR) (no emesis, no rescue) was 100% for the acute period (24 hours post chemotherapy) and 80% for the delayed period (days 2–5 post chemotherapy) in 10 patients receiving highly emetogenic chemotherapy (HEC) (cisplatin, ≥ 70 mg/m2). CR was also 100% for the acute period and 85% for the delayed period in 20 patients receiving moderately emetogenic chemotherapy (MEC) (doxorubicin, ≥ 50 mg/m2). Nausea was well controlled in the patients receiving HEC with no patient having more than minimal nausea (≤2 on scale of 0–10, M.D. Anderson Symptom Inventory, MDASI) in the acute or delayed periods. Nausea was also well controlled in patients receiving MEC with minimal or no nausea in 85% of patients in the acute period and 70% in the delayed period. There were no Grade 3 or 4 toxicities and no significant pain, fatigue, disturbed sleep, memory changes, dyspnea, lack of appetite, drowsiness, dry mouth, mood changes or restlessness experienced by the patients. CR and control of nausea in subsequent cycles of chemotherapy (25 patients, cycle 2; 25 patients, cycle 3; 21 patients, cycle 4) were equal to or greater than cycle 1. Conclusions: Olanzapine is safe and highly effective in controlling acute and delayed CINV in patients receiving HEC and MEC. No significant financial relationships to disclose.
Higher CD3 cell counts in apheresis collection in relation to superior survival in patients with multiple myeloma.
Authors: Sharon Kim, Morie Gertz, Angela Dispenzieri, Martha Lacy, Francis Buadi, Suzanne R. Hayman, David Dingli, Prashant Kapoor, Jeffrey Winters, Dennis A. Gastineau, William J. Hogan, Luis F. Porrata, Shaji Kumar
Journal: Journal of Clinical Oncology (2015)

11085 Background: High dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) remain a standard of care for patients with multiple myeloma (MM). While the impact of transplant is primarily thought to be related to dose intensity, immunological reconstitution also plays a major role. We examined the impact of CD3 content of apheresis product on outcomes. Methods: Patients (pts, n = 1187) diagnosed with MM between 2006 and 2014 who had a stem cell collection were included. Overall survival (OS) outcomes were correlated with total CD3 collected, CD3/CD34 ratio in the collection, and CD3 infused. Results: Among all 1187 pts included (median age 61 years, 57% male), the median CD3 and CD34 content was 4.6 x108/kg and 8.3 x106/kg, respectively. Overall, 886 (75%) had undergone HDT. Since the total CD3 count depends on the total goal, we examined the impact of CD3/CD34 ratio on outcomes. The median OS from ASCT was 90 months for those with a ratio of > 5 x103, compared with 68 months for the rest (p < 0.01). Specifically looking at the first day CD3 counts, median OS was not reached for those patients with > 2.3 x108/kg compared with 68 months for the rest (p < 0.01). In addition, CD3 dose infused was also prognostic for OS. In a multivariable analysis, the prognostic value was independent of the disease status for HDT, timing of HDT, and for the number of prior therapies. Given that the CD3 collection can be a surrogate marker for the immune system, we examined the impact of CD3 content on patients who collected without receiving HDT, estimating the OS from collection date. Among the 301 pts not treated with HDT, the OS from the collection date was not affected by the total CD3 dose or CD3/CD34 ratio, but remained strongly prognostic for those who had HDT. Conclusions: The results suggest that we should not only collect enough CD34 for hematopoietic recovery, but also enough CD3 for immunologic recovery with direct impact in clinical outcomes in MM patients undergoing ASCT.
Clinical efficacy of gene-modified stem cells in adenosine deaminase–deficient immunodeficiency
Authors: Kit L. Shaw, Elizabeth Garabedian, Suparna Mishra, Provaboti Barman, Alejandra Davila, Denise Carbonaro, Sally Shupien, Christopher Silvin, Sabine Geiger, Barbara Nowicki, E. Monika Smogorzewska, Berkley Brown, Xiaoyan Wang, Satiro de Oliveira, Yeong Choi, Alan Ikeda, Dayna Terrazas, Pei-Yu Fu, Allen Yu, Beatriz Campo Fernandez, Aaron R. Cooper, Barbara Engel, Greg Podsakoff, Arumugam Balamurugan, Stacie Anderson, Linda Muul, G. Jayashree Jagadeesh, Neena Kapoor, John Tse, Theodore B. Moore, Ken Purdy, Radha Rishi, Kathey Mohan, Suzanne Skoda-Smith, David Buchbinder, Roshini S. Abraham, Andrew Scharenberg, Otto O. Yang, Kenneth Cornetta, David Gjertson, Michael Hershfield, Rob Sokolic, Fabio Candotti, Donald B. Kohn
Journal: Journal of Clinical Investigation (2017)

BACKGROUND. Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase–deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study.
Treatment of 9-bromonoscapine induces irreversible mitotic arrest and apoptosis in cigarette smoke condensate-transformed human breast epithelial cells
Authors: Aruna Jaiswal, Ritu Aneja, Asha Multani, Shahnjayla Connors, Harish Joshi, Sen Pathak, Satya Narayan
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

2243 

In previous studies, we have shown that cigarette smoke condensate (CSC), a surrogate of cigarette smoke, transforms in vitro the spontaneously immortalized normal breast epithelial cell line, MCF10A. In the present study, we have determined the chemotherapeutic efficacy of 9-Bromonoscapine, a naturally occurring alkaloid, on MCF10A and CSC-transformed MCF10A-CSC3 cells. The results from cytogenetic analysis showed that 9-Bromonoscapine-induced polyploidy and chromosomal fusions in MCF10A-CSC3 cells, while MCF10A cells remained unaffected. By using fluorescence staining we further demonstrated that MCF10A-CSC3 cells were susceptible to mitotic catastrophe on exposure to 9-Bromonoscapine and failed to recover after the withdrawal of the drug. MCF10A-CSC3 cells also exhibited 9-Bromonoscapine-induced aberrant multi-polar spindle formation which irreversibly impaired the alignment of replicated chromosomes to the equatorial plane and resulted in cell death. On the other hand, MCF10A cells, which also showed some metaphase catastrophe of 9-Bromonoscapine treatment, recovered fairly well after the withdrawal of the drug. The results from florescence activated cell sorting analysis reconfirmed that MCF10A-CSC3 cells were more susceptible to cell death as compared to MCF10A cells. Our results suggested that the decreased level of cdc2/cyclin B1 and cdc2 kinase activity were responsible for the 9-Bromonoscapine-induced mitotic cell arrest leading to cell death in MCF10A-CSC3 cells. This study explores the underlying mechanism of 9-Bromonoscapine-induced mitotic catastrophe in MCF10A-CSC3 cells and suggests that 9-Bromonoscapine can be developed as a potential chemotherapeutic agent for cigarette smoke-induced breast carcinogenesis. The financial support for these studies was provided to Satya Narayan by the grants from NCI-NIH (CA-097031 and CA-100247).
Pazopanib (P) and cisplatin (CDDP) in patients with advanced solid tumors: A UNICANCER phase I study.
Authors: Veronique Dieras, Thomas Bachelot, Mario Campone, Nicolas Isambert, Florence Joly, Christophe Le Tourneau, Philippe Alexandre Cassier, Emmanuelle Bompas, Pierre Fumoleau, Sabine Noal, Christine Orsini, Marta Jimenez, Diane Charlotte Imbs, Etienne Chatelut
Journal: Journal of Clinical Oncology (2014)

2583 Background: P is an effective anti-angiogenic agent currently investigated in a wide variety of tumors outside its authorized indication. In a dose-escalation phase I study, we investigated the safety and tolerability of combining P with CDDP. Methods: Patients (pts) with metastatic refractory solid tumors eligible for CDDP chemotherapy were treated with oral P given once daily, in fasted condition, starting 8 days (d) before the first CDDP infusion. CDDP was given every 3 weeks (q3w) in a 1-hour iv infusion. Five dose levels (DL) were planned to investigate the occurrence of dose limiting toxicities (DLT) over cycle 1 and 2, and to determine the maximum tolerated dose (MTD). Results: 35 pts were enrolled with median age of 59 y., PS≤1. Tumor types were: ovary (8), H&N (5), sarcoma (5), breast (4), colorectal (4), choroidal melanoma (3), other (6). DLs explored are shown in the Table. MTD was confirmed at DL1. An inverted schedule (IS) was added at the MTD starting with CDDP followed by P to explore PK interaction. DLT were 2 Grade (G) 3 ALAT elevation, one associated with G4 hyponatremia (DL1 and DL2 respectively), 2 G3 thrombopenia + neutropenia (DL2), 1 G2 neutropenia (DL2), 2 G3 pulmonary embolism (DL1 and IS). Mean number of 21d-cycles was 3 for CDDP and 4.7 for P. 15 pts discontinued treatment for unacceptable toxicity, 5 pts are still under treatment. 2 complete (DL2) and 2 partial responses (DL1 and DL2) were achieved. Mean (CV% for interindividual variability) CDDP clearance was 13.6 L/h (27%) and not influenced by P. However, mean of P clearance was 0.78 L/h (69%) at d-1 (before CDDP), 24.5% lower at d1 (CDDP + aprepitant), and 30% lower at d2 (aprepitant), likely due to competitive inhibition of P metabolism and efflux by aprepitant. The plasma P exposures observed at 400 mg (at d-1) were similar to those observed at 800 mg of P during the first-in-man phase 1 [Hurwitz et al]: 676.2 µg.h/mL (47%) vs. 743.3 µg.h/mL (76%), respectively. A nonsignificant trend of higher P AUC was observed in patients with DLT. Conclusions: Despite activity observed in some patients, the potential to combine P and CDDP appears limited due to the safety profile and the PK interactions within the combination. Clinical trial information: NCT01165385. DL P mg/d CDDP mg/m² n 1 400 75 13 -1 400 60 3 2 600 75 6 -2 200 75 4 IS 400 75 9