tbuckley/cabot-search huggingface dataset:
Use and perceptions of complementary and alternative medicine in a community cancer center.
Authors: Mike Cusnir, Christina Pozo-Kaderman, Irene Sullivan, Elaine Vinas
Journal: Journal of Clinical Oncology (2012)

e19646 Background: Studies over the past 10 years in the general population showed use of complementary and alternative medicine (CAM) to no more than 42% with the largest study reporting only 28% use in adults. In the cancer population one of the largest studies showed that 83.3% had used at least one CAM approach. After excluding spiritual practices and psychotherapy, 95.8% of participants were aware of CAM and 68.7% of those had used CAM. However most of this information has been obtained in academic medical centers that would be biased since the use of CAM has also been reported to vary by location, education and socio-economic status. Methods: We evaluated with a questionnaire similar to the one use by Richardson et al, in 2000 looking for prevalence and predictors of CAM use in a south Florida community cancer center with a culturally diverse patient population, many of Hispanic descent, we also evaluated the opinion about participating in CAM clinical trials.150 consecutive patients coming to the cancer center were given a questionnaire of which 112 are evaluable at the time of this report. Results: Average age was 66 years, 50 % of the patients were males, 56% of the patients were actively on chemotherapy, 10% on hormonal manipulations and 33% were not actively on treatment. 52% had heard of the term CAM, 34 % had heard the term integrative medicine, 18% had use CAM for their cancer treatment. Only 27% of the patients had discussed the use or interest in use of CAM with one of the health care providers. 59% expressed interest in participating in CAM clinical trials. Regarding specific therapies that the patients had used to “treat cancer” 8% had used dietary interventions, 15% had used movement therapies (TaiChi, yoga, etc.), 12% use of mind-body practices, 25% had used herbal and vitamin supplements and 25 % had used spiritual practices. Conclusions: Our study population had slightly lower use of CAM than in academic centers however the type of practices used appears to be different with increased use of mind/body and movement techniques over spiritual practices which might be a cultural effect. We also found a strong interest and will to participate in clinical trials that should be a window of opportunity to test these therapies in community settings.
The histone methyltransferase EZH2 and breast cancer development: EZH2 and H3K27me3 correlation with prognosis of ER-positive cancers.
Authors: Woo Kyun Bae, Sang-Hee Cho, Ik-Joo Chung, Priscilla A Furth, Lothar Hennighausen
Journal: Journal of Clinical Oncology (2014)

e11537 Background: Enhancer of zeste homolog 2 (EZH2) is known to catalyze trimethylation of histone H3 lysine 27 (H3K27me3) and demethylation is catalyzed by UTX. EZH2 levels are frequently elevated in breast cancer and have been proposed to control gene expression through regulating repressive H3K27me3 marks. However, it is not known if EZH2 and UTX are mandatory for H3K27me3 marks or whether breast cancers with different levels of H3K27me3, EZH2 and UTX exhibit different biological behaviors. Methods: Samples of human breast cancers and genetically engineered mice were used to investigate these questions. Global levels of H3K27me3, EZH2 and UTX were measured in 146 cases of invasive ductal breast cancer with complete clinicopathological data and follow up information and its prognostic significance. We made tissue microarry and used it for evaluating the expression of proteins. Survival analyses were additionally stratified by ER status to account for the fact that ER expression fundamentally defines clinically distinct diseases in breast cancer. Results: H3K27me3 expression was higher in HER2 negative. EZH2 expression was higher in LN+, tumor size > 20mm, higher tumor grade and stage. In Cox regression model, H3K27me3 and EZH2 expressions were identified as independent prognostic factors for overall survival in entire cohort and ER-postive cancers. Combining low H3K27me3 and high EZH2 expression was also significantly associated with poorer survival rate. However, UTX expression was not significantly associated with prognosis and there were no correlation between H3K27me3 and EZH2/UTX expression. To address the causative role of EZH2 in establishing H3K27me3 marks in mammary epithelium and the development of breast cancer Brca1 and Ezh2 were deleted in mammary stem cells in mice. Brca1-deficient tumors developed in the absence of EZH2 and H3K27me3 levels were unaltered. Conclusions: The low H3K27me3 and high EZH2 may serve as a marker for poorer prognosis for overall survival in breast cancers, especially ER+. Genetic evidence demonstrates that EZH2 is not the mandatory H3K27 methyltransferase in normal and transformed mammary epithelium.
Prognostic factors of survival in 236 advanced hepatocellular carcinoma patients enrolled in prospective clinical trials of systemic therapy
Authors: Z. Lin, D. Chang, Y. Shao, C. Hsu, C. Hsu, K. Yeh, C. Yang, R. Hong, A. Cheng
Journal: Journal of Clinical Oncology (2009)

e15632 Background: Hepatocellular carcinoma (HCC) is a common malignant disease. Promising results of prospective clinical trials using systemic therapy for patients with advanced HCC are emerging. The aim of this study was to explore prognostic factors of survival in advanced HCC patients eligible for clinical trials of systemic therapy. Methods: From December 1990 to July 2005, 236 patients with unresectable HCC were enrolled into 6 phase II trials of systemic therapy using the following regimens: (1) oral etoposide + tamoxifen, (2)doxorubicin + tamoxifen, (3)IFN-α2b + doxorubicin + tamoxifen, (4)pegylated liposomal doxorubicin, (5)thalidomide, and (6)arsenic trioxide. Univariate and multivariate analyses of 23 relevant clinical characteristics/staging systems were used to identify prognostic factors of survival. Results: Baseline characteristics: median age 55; male/female: 192/44; HBsAg(+) 71%; anti-HCV(+) 30%; Okuda stage I/II/III: 42%/55%/3%; AJCC stage III/IV: 30%/61%; BCLC stage B/C/D: 1%/94%/5%; CLIP score 0–3/4–6: 70%/30%; portal vein thrombosis 53%; extrahepatic metastasis 59%; prior chemoembolization 46%. The objective response rate according to WHO criteria was 11.4%. The median overall survival was 118 days (95% CI, 103–133). In the multivariate analysis, significant predictors of a shorter overall survival were: HBsAg(+) with a hazard ratio (HR) = 1.808 (95% CI, 1.121–2.916; P= 0.015), symptomatic with HR = 1.745 (95% CI, 1.072–2.840; P= 0.025), ECOG≥2 with HR = 1.763 (95% CI, 1.040–2.988; P= 0.035), and high BCLC stage with HR = 3.282 (95% CI, 1.129–9.541; P= 0.029). Conclusions: Patients with advanced HCC who are eligible for systemic therapeutic trials have patient- and disease-related prognostic factors. Positive HBsAg, symptomatic, ECOG performance≥2, and high BCLC stage predict a shorter overall survival. No significant financial relationships to disclose.
The outcome of special histologic types of triple-negative breast cancer (TNBC).
Authors: Katarzyna Pogoda, Anna Niwinska, Magdalena Murawska, Wojciech Olszewski, Zbigniew Nowecki
Journal: Journal of Clinical Oncology (2014)

1122 Background: Triple-negative breast cancer (TNBC) is a heterogeneous disease. Knowledge of the outcome of special histological subtypesof TNBC can facilitate tailored adjuvant treatment. The aim of the study was to determine recurrence rate and overall survival of special histological subtypes of TNBC in order to select those with excellent and the worst prognosis. Methods: Of 4,563 consecutive breast cancer patients diagnosed in Cancer Center and Institute of Oncology in Warsaw, Poland, between the years 2005 and 2008, 502 patients (9%) were TNBC (ER-/PR-/HER2-negative). Median follow-up was 7 years (range 5–9 years). 426 cases with known histological types were selected and analyzed in terms of the disease free and overall survival using the Kaplan-Meier method. Competing risk analysis was performed in order to assess the risk of recurrence and the comparison between types. Results: From 426 TNBC subtypes, 352 (82%) cases were classified as ductal not otherwise specified (NOS), 21 (5%) were classified as lobular, 17 (4%) were classified as metaplastic, 10 (2.3%) were classified as medullary, 7 (1.6%) as apocrine, 6 (1.4%) as papillary, 4 (0.9%) as neuroendocrine, 2 (0.5%) as cribriform and 2 (0.5%) were classified as mucinous. 5-year DFS and OS of ductal NOS type was 73% and 62%, respectively. 5-year DFS was the best for patients with apocrine (100%), medullary (100%) and neuroendocrine (100%) types while it was the worst in papillary (50%) and lobular (68%) TNBC. 5-year OS was the best in apocrine (90%) and medullar (100%) types and was the worst in papillary (17%) and lobular (61%) types. In metaplastic TNBC 5-year DFS and OS was 79% and 65%, respectively. Taking into account competing risk of death and different clinical stages of the disease, the risk of recurrence was the highest in patients with lobular TNBC (HR=2.83, p=0.04). Conclusions: The diagnosis of special types of TNBC is associated with different outcome if compared with ductal NOS type. Medullary and apocrine types had excellent prognosis while lobular TNBC seems to be the most aggressive and requires intensive treatment. Histological special type of TNBC should be taking into consideration when choosing adjuvant treatment, apart from specified other prognostic factors.
Pharmacokinetics of escalated dose of imatinib in patients with advanced gastrointestinal stromal tumors.
Authors: Changhoon Yoo, Min-Hee Ryu, Baek-Yeol Ryoo, Inkeun Park, Mo Youl Beck, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2012)

10085 Background: Although escalated dose (ED, 800 mg daily) of imatinib (IM) is one of important options in resistant gastrointestinal stromal tumors (GIST) on standard dose (SD, 400mg daily), there has been lack of pharmacokinetic data at ED. We therefore explore the potential relationship between IM plasma trough level (C min ), and clinical outcomes or toxicities in patients treated with ED. Methods: Between 2008 and 2011, steady-state IM C min was measured in 66 patients with GIST who received ED of IM using liquid chromatography-tandem mass spectrometry. Percent change from IM C min at SD was calculated in 43 patients that both SD and ED IM C min were measured. The association with efficacy and toxicity was analyzed with grouping patients into quartiles according to IM C min at ED and percent change. Results: Median age was 59 years (range, 36–77) and 40 patients were male. KIT exon 11 and 9 mutation was detected in 32 and 18 patients, respectively. At ED, partial response was achieved in 4 patients (6%) and stable disease was in 32 patients (48%). The median progression-free survival was 4.2 months (95% CI, 1.8-6.6) and overall survival was 38.5 months (95% CI, 7.6-69.3). The mean (± standard deviation) IM C min at ED was 3552 (± 1540) ng/mL. IM C min was significantly increased after dose escalation (p &lt;0.001), and mean percent change from IM C min at SD was 162% (± 100). Body surface area (p=0.01), hemoglobin (p=0.001), and neutrophil count (p=0.006) were significant covariates for IM C min at ED in multivariate analysis. The group of quartiles of IM C min at ED and percent change was not associated with response and survival outcomes. However, grade 3-4 hematologic or grade 2-4 non-hematologic toxicity was observed in 9% (1/11) of patients in the lowest percent change quartile (Q1, &lt;90%) compared with 56% (18/32) in Q2 to Q4 (p=0.012), although absolute values were not associated with toxicity. Conclusions: In GIST patients treated with ED of IM, IM C min was not associated with response and survival. Clinically significant toxicity following dose escalation was correlated with percent change of IM C min , rather than absolute values. Monitoring of IM C min might help to predict or manage ED of IM induced toxicity.
Allogeneic or autologous transplantation as first-line therapy for younger patients with peripheral T-cell lymphoma: Results of the interim analysis of the AATT trial.
Authors: Norbert Schmitz, Maike Nickelsen, Bettina Altmann, Marita Ziepert, Kamal Bouabdallah, Christian Gisselbrecht, S bastien Maury, Guillaume Cartron, Emmanuel Gyan, Arnaud Jaccard, Laurence Sanhes, Philippe Gaulard, Andreas Rosenwald, Lorenz Truemper, Bertram Glass, Peter Reimer, Wolfgang Herr, Martin Wilhelm, Olivier Tournilhac
Journal: Journal of Clinical Oncology (2015)

8507 Background: AlloSCT gives encouraging results in pts with relapsed PTCL. We did the AATT (Autologous or Allogeneic Transplantation in T-Cell Lymphoma) study in newly diagnosed PTCL and present results of an interim analysis leading to termination of the trial. Methods: We compared alloSCT with autoSCT in younger pts with PTCL. Pts were randomized after enrolment. Treatment was four courses of CHOEP-14. Pts achieving CR/ PR/ SD proceeded to DHAP and stem cell collection in pts randomized to autoSCT or without suitable (HLA 10/10) donor. BEAM high-dose therapy and autoSCT or myeloablative conditioning and alloSCT followed within 4-6 weeks. Results: 58/104 pts were eligible: median age was 50 years, 64% of pts were male. 11/30 pts randomized to autoSCT did not proceed to transplantation because of progressive disease / no response (n=8), infection (n=1) or change of histology (n=2). 13/28 pts (46%) randomized to alloSCT received it. Fifteen pts were not allografted due to progressive disease (n=10) or l...
Effect of ketoconazole administration on the pharmacokinetics (PK) and pharmacodynamics (PD) of bortezomib in patients with advanced solid tumors
Authors: G. S. Chatta, M. E. Rader, C. P. Belani, S. Ramalingam, E. X. Chen, M. R. Cooper, L. L. von Moltke, L. A. Musguire, M. J. Egorin, M. D. Karol
Journal: Journal of Clinical Oncology (2007)

13016 Background: Bortezomib (btz; VELCADE) is a first-in-class small molecule proteasome inhibitor used to treat patients with multiple myeloma and mantle cell lymphoma. In vitro and in vivo studies indicate that btz is primarily metabolized by CYP3A4 and CYP2C19. We conducted a study to evaluate the effect of inhibition of CYP3A4 with ketoconazole (keto) on the PK of btz in humans. Methods: The study enrolled patients with advanced malignancies for whom standard therapy was not available. Patients received btz 1.0mg/m 2 (IV) on days 1, 4, 8, and 11 of a 21-day cycle, and were randomized to receive keto 400mg (PO) on days 6, 7, 8, and 9 of either the first or second cycle of treatment. Blood samples for plasma btz determination were collected over 72 hours following the Day 8 dose in Cycles 1 and 2. PK parameters were computed non-compartmentally. PD parameters were derived from an E max model of percentage proteasome inhibition in whole blood. Results: Of the 21 patients enrolled, 13 had sufficient PK sampling in Cycles 1 and 2 to assess the effect of keto on the PK of btz. No statistically significant difference in AUC 0–72h for btz ± keto was observed (p=0.2248). The mean AUC 0–72h ratio was 1.22 (90% CI, 0.92–1.61). The exposure-PD relationships for btz ± keto were similar (Table). Adverse events were similar in the presence and absence of keto. Conclusions: Although the AUC 0–72h difference was not statistically significant, the 90% CI for the AUC 0–72h ratio extends beyond the FDA- specified range of 0.80–1.25 for DDI studies, precluding a declaration of no effect. The presence of a strong CYP3A4 inhibitor increased mean btz exposure by only 22% and had no apparent effect on the exposure-PD relationship. [Table: see text] No significant financial relationships to disclose.
The efficacy of first-line chemotherapy in recurrent pancreatic cancer after S-1 adjuvant chemotherapy.
Authors: Ryo Kanata, Masato Ozaka, Seita Kataoka, Kazunaga Ishigaki, Ikuhiro Yamada, Takashi Sasaki, Masato Matsuyama, Kouichi Takano, Naoki Sasahira
Journal: Journal of Clinical Oncology (2017)

475 Background: In Japan, adjuvant chemotherapy with S-1 for 6 months is standard care for resected pancreatic cancer. However, the efficacy of chemotherapy for recurrent pancreatic cancer(RPC) after adjuvant S-1 chemotherapy is not well evaluated. Methods: Medical records were retrospectively reviewed for consecutive patients who had RPC after adjuvant S-1 treatment and received chemotherapy between April 2013 and July 2016. Recurrence free interval (RFI) was defined as the interval from adjuvant S-1 initiation to cancer recurrence. Overall survival (OS) and progression free survival (PFS) after 1 st line chemotherapy for RPC were compared between patients with RFIs of shorter than 6 month (Group S) and longer than 6 months (Group L). Results: In the 53 patients evaluated, the median duration of adjuvant S-1 chemotherapy was 5.1 months, and the median RFI was 8.3 months. After recurrence, they received Gemcitabine alone (20 patients), Gemcitabine+nab-paclitaxel (28 patients), modified FOLFIRINOX (one patient), and other regimen (4 patients). In all patients, the median PFS was 7.3 months and the median OS was 14.8 months. When compered in two groups (group S and group L), median OS in group S and group L was 6.7 months (95% confidence interval(CI): 4.2-12.9) and NA (95% CI: 13 months-NA) , respectively (p &lt; 0.001), and median PFS was 3.8 months (95%CI: 2.5-9.1) and 7.3 months (95%CI: 3.9-15.3), respectively (p = 0.11). Multivariate Cox regression analysis revealed CEA &lt; 4.0 mg/dl before chemotherapy and an RFI of ≥ 6 months were significantly associated with longer survival. Conclusions: These data suggest that RFI &lt; 6 months is a surrogate marker for a poor prognosis in patients with RPC.
Efficacy and safety of enzalutamide (ENZA) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with abiraterone acetate (Abi): A multicenter, single-arm, open-label study.
Authors: Johann S. De Bono, Simon Chowdhury, Susan Feyerabend, Tony Elliott, Enrique Grande, Amal Melhem-Bertrandt, Benoit Baron, Mohammad Hirmand, Patrick Werbrouck, Karim Fizazi
Journal: Journal of Clinical Oncology (2017)

165 Background: This phase 4, multicenter, single-arm, open-label study evaluated the efficacy and safety of ENZA in patients (pts) with progressing mCRPC previously treated with Abi. Methods: All pts maintained castration therapy with luteinizing hormone-releasing hormone for the duration of the trial or had a bilateral orchiectomy. Pts were required to have progressive disease at study entry and ≥ 24 weeks of Abi treatment prior to receiving 160 mg/day ENZA. Prior chemotherapy was allowed. The primary end point was radiographic progression-free survival (rPFS). The secondary end points were overall survival (OS), prostate-specific antigen (PSA) response, and time to PSA progression. Safety was also assessed. Results: A total of215 pts were enrolled; 214 were treated with ENZA (median age, 73 years). The analysis was performed on data up to 48 weeks after the last pt started ENZA treatment. Median duration of prior Abi therapy was 54 weeks. The median duration of ENZA treatment was 5.7 months: 12 months in PSA responders and 4.6 months in non-PSA responders. 16% of pts received treatment for ≥ 1 year. The most common reason for treatment discontinuation was disease progression (65%). Median rPFS was 8.1 months (95% CI 6.1, 8.3). Median OS was not reached in the overall population and 75% of pts were alive 1 year after treatment initiation. PSA response (confirmed or unconfirmed) rate was 26.5% (48/181). The median time to PSA progression was 5.7 months (95% CI 5.6, 5.8). The overall objective response rate in pts with measurable disease at study entry was 12%. The most common treatment emergent adverse events (TEAEs) were fatigue (32%), decreased appetite (25%), asthenia (18%), back pain (17%), and arthralgia (16%). ENZA was primarily discontinued due to TEAEs in 8% of pts. No seizures were reported. Conclusions: In this study, ENZA remained active in pts with mCRPC previously treated with Abi. Median rPFS in pts with prior chemotherapy was consistent with previously reported data of ENZA in pts with mCRPC and prior chemotherapy/Abi therapy.Reported TEAEs were consistent with the known safety profile of ENZA. Clinical trial information: NCT02116582.
An Integrated Analysis of Cardio-Vascular Adverse Events of Carfilzomib, Cyclophosphamide and Dexamethasone in Elderly Newly Diagnosed Myeloma Patients Enrolled in 3 Phase I/II Trials
Authors: Sara Bringhen, Maria Teresa Petrucci, Nicola Giuliani, Angelo Michele Carella, Mariella Genuardi, Tommaso Caravita di Toritto, Alessandra Malfitano, Pellegrino Musto, Roberto Ria, Giovannino Ciccone, Paola Omedé, Massimo Offidani, Caterina Musolino, Anna Marina Liberati, Lorenzo De Paoli, Stelvio Ballanti, Piero Galieni, Michele Cavo, Concetta Conticello, Roberto Foà, Paolo Corradini, Gianluca Gaidano, Antonio Palumbo, Pieter Sonneveld, Mario Boccadoro
Journal: Blood (2016)
A phase II pilot study of fosaprepitant (F) for the rescue of acute nausea and vomiting with moderately (MEC) or highly emetogenic chemotherapy (HEC) in adults.
Authors: Joseph S. Bubalo, Ian D. Schnadig, Gabrielle Meyers, Andy I. Chen, Brandon M. Hayes-Lattin, Christopher W. Ryan, Jocelyn Digregorio, Richard T. Maziarz
Journal: Journal of Clinical Oncology (2013)

e20627^ Background: Patients receiving MEC or HEC continue to have breakthrough nausea and emesis despite antiemetic prophylaxis. Few trials have evaluated the efficacy of rescue antiemetics after failed prophylaxis. F, a prodrug of the neurokinin-1 antagonist (NK1a), aprepitant is FDA-approved for the prevention of acute and delayed nausea and vomiting associated with MEC and HEC. F’s safety and efficacy in the prophylactic setting make F an attractive potential rescue therapy. Methods: F 150mg was infused as the initial rescue agent in eligible patients receiving MEC or HEC who had either emesis or nausea despite guideline-based prophylaxis with a 5HT-3 antagonist and dexamethasone. The primary endpoint was improved nausea on a visual analogue scale (VAS) at 2 hours. Secondary endpoints included: VAS at 12 and 24 hrs, rescue medication use, emesis, nutritional intake, adverse events, and proof of the study design as a viable methodology. Results: Eleven adult patients, 6 males and 5 females, were treated per protocol and evaluable for the 24 hour study period. Chemotherapy regimens included HiDAC, R-CHOP, epirubicin/ifosfamide, EPOCH, R-ICE, 7+3, VAC, and HyperCVAD. 3 patients were treated for emesis and 8 for nausea. 91% of patients had improved nausea at 2 hrs, 100% at 12 hrs and 63.6% at 24 hrs. F prevented further emesis in 2 of 3 patients and no patient with initial nausea had subsequent emesis. 9 of 11 (81.8%) patients required additional rescue medication during the study period, mainly due to nausea. Appetite was improved in 8/11 patients. Food and fluid intake improved in 5/11. Adverse effects included headache 18%, dizziness 18%, hiccups 9%, indigestion 9%, and 1 case ifosfamide encephalopathy. The study design required greater than anticipated consented patients due to the success rates of standard antiemetic therapy. Conclusions: F improves breakthrough nausea and related symptoms, and may prevent further emesis but was suboptimal as a single agent in that the majority of patients required a second rescue agent within 24 hrs. Complete response, defined as no emesis and no rescue therapy, may be a more clinically relevant primary endpoint in future trial designs. Clinical trial information: NCT00939302.