tbuckley/cabot-search huggingface dataset:
Racial and age specific differences in localized and metastatic prostate cancer incidence: 1988-2013.
Authors: Marc Dall'Era, Ralph deVere White, Danielle Rodgriguez, Rosemary Donaldson Cress
Journal: Journal of Clinical Oncology (2017)

211 Background: The United States Preventive Services Task Force (USPSTF) recommended against routine PSA based prostate cancer screening in all men in 2012. This led to dramatic reductions in screening and rates of localized disease across all clinical risk groups. We sought to study the impact of this on rates of metastatic disease, specifically by patient race and age. Methods: We analyzed new prostate cancer incidence by stage at diagnosis between 1988-2013 within the Cancer Registry of Greater California. We further stratified cases by four major race/ethnicity groups (non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic and non-Hispanic Asian/PI (API)) and age. Incidence rates were calculated and compared per 100,000 and age-adjusted to the 2000 US Standard Population. Joinpoint regression was used to detect changes in incidence and to calculate the average percent change (APC). Results: Adjusted rates of remote prostate cancer incidence for NHW men increased slightly in the most recent decade (+0.28%) after steady declines in previous years with the inflection point occurring in 2002, however this was not statistically significant. In contrast, incidence of remote prostate cancer continued to decline for NHB (-2.73%), Hispanic (-2.04%), and API (-1.45%) men. The greatest increase of +1.1% a year since 2002 was observed for NHW men under age 65. The incidence of localized prostate cancer declined for all race/ethnicity groups over the most recent time period and also declined in all age groups. After remaining relatively flat since 1992, incidence of localized prostate cancer among NHW men declined by over 8% per year starting in 2007 compared with a more gradual decline of -3.52% a year since 2000 for NHB, and more recent declines of -14.41% and -16.64% for Hispanic and API men, respectively. Incidence of regional stage cancer also declined in all groups, but less dramatically. Conclusions: Incidence rates of newly metastatic prostate cancer have not significantly changed since PSA screening declined in the US although we noted a slight upward trend primarily for younger, white men since 2002.
A phase I/II trial of olaparib in combination with eribulin in patients with advanced or metastatic triple negative breast cancer (TNBC) previously treated with anthracyclines and taxanes: First results from phase I.
Authors: Hiroyuki Yasojima, Harukaze Yamamoto, Norikazu Masuda, Kenjiro Aogi, Masato Takahashi, Kan Yonemori, Masahiro Takeuchi, Akinobu Hamada, Kenji Tamura, Tamie Sukigara, Ritsuko Nagasaka, Rie Nakano, Yukie Tsujimoto, Yuka Morioka, Kiyomi Higuchi, Yasuhiro Fujiwara
Journal: Journal of Clinical Oncology (2015)

1038 Background: Olaparib is a PARP inhibitor which has been reported to be effective against some solid tumors and the recommended dose is 300 mg bid as monotherapy. Eribulin is currently a global standard drug after treatment with anthracyclines and taxanes in advanced TNBC; however, olaparib has also shown promising efficacy in breast cancer with BRCA mutations, which are associated particularly with TNBC. Therefore, we designed this phase I/II trial (UMIN000009498) with an expectation of synergistic effects. Methods: By the traditional 3+3 design, 1.4 mg/m2 of eribulin was administered intravenously on days 1 and 8. Olaparib tablet was orally administered twice daily according to dose escalation method from level 1: 25 mg bid to level 7: 300 mg bid. Dose-limiting toxicities (DLTs) consist of neutropenia G4 over seven days, thrombocytopenia G4, febrile neutropenia, non-hematotoxicity G3/4, administration of eribulin deferred on both days 8 and 15 due to adverse events, and onset of cycle 2 delayed over 14 days. Results: Twenty-four patients were enrolled from February 2013 to April 2014. The median age was 52 years old (range: 36 to 77). The median number of prior chemotherapy regimens was 3 (range: 2 to 7). Significant adverse events (G3 or higher) were neutropenia (87.5%), febrile neutropenia (20.8%) and anemia (16.7%). Nausea (54.2%) of any grade was also observed, for which most subjects required antiemetic. There was only one DLT observed through phase I part; a subject in level 7 could not be administered eribulin on both day8 and 15 due to neutropenia. In respect to efficacy, PR in 4 patients and SD in 12 patients were observed. The response rate was 18.2% [n = 4/22], while the disease control rate (PR and SD) was 72.7% [n = 16/22]. Cmax and AUC of olaparib were correlated with its dose. PK parameters of both eribulin and olaparib were not influenced by each other. Conclusions: RD of olaparib was estimated to 300 mg bid because MTD was not attained. Now we are conducting phase II part. Enrollment has already completed and the final results will be available reported in the third quarter of 2015. Clinical trial information: 000009498.
Association of PIK3CA mutations and age with the occurence of second primary lung cancer (SPLC).
Authors: Marc Christiaan Allardt Bos, Masyar Gardizi, Matthias Scheffler, Lucia Nogova, Thomas Zander, Lukas Carl Heukamp, Hans-Ulrich Schildhaus, Sabine Merkelbach-Bruse, Jana Fassunke, Elke Binot, Andreas Schlesinger, Thomas Geist, Kato Kambartel, Roland Schnell, Holger Schulz, Dirk M. Behringer, Monika Serke, Stephan H. Schmitz, Winfried Randerath, Juergen Wolf
Journal: Journal of Clinical Oncology (2013)

1589 Background: The incidence of SPLC in Germany was reported to be 1.2 per 100,000 inhabitants in 2007 and the prevalence of second primary cancers reported by the US International Cancer Institute's Surveillance, Epidemiology and End Results Program has more than doubled over the last 25 years. Recently there has been tremendous progress in the ability to detect driver mutations in lung cancer and large studies presented the frequencies of driver mutations in unselected patient populations. We conducted an association study of known genetic driver events and clinical characteristics with the occurence of SPLC. Methods: Within the Network Genomic Medicine Lung Cancer, a local molecular screening network encompassing hospitals and office-based oncologists in the catchment area of the Center for Integrated Oncology Köln Bonn, we retrospectively reviewed the medical records of 375 molecularly annotated NSCLC patients for their SPLC status and clinical characteristics (age at diagnosis, histology, sex, smoking status). Molecular analysis for lung adenocarcinoma included the EGFR, ALK, BRAF, KRAS and PIK3CA status and for squamous cell lung cancer the FGFR1 and PIK3CA status. Results: 84 of 375 (22,4%) patients were SPLCs. The median age of SPLC diagnosis was 70 yrs. (Range 53 - 85 yrs.) and differed significantly from the rest of the population with a median age of 65 yrs. (Range 28 - 86 yrs.). The frequency of SPLCs was not significantly different between males and females (p = 0,259). In univariate logistic regression analysis active and former smoking, positive PIK3CA mutation and FGFR1 amplification status as well as age were significantly associated with the occurrence of SPLC. In a multivariate logistic regression analysis including the variables mentioned above only PIK3CA mutations (OR 9,48 95% CI 1,83 - 49,1) (p = 0,007) and age (OR 1,06 95% CI 1,03 - 1,1) (p = 0,015) could be confirmed to be independent prognosticators for the occurrence of SPLCs. Conclusions: The occurrence of SPLC was associated with age and PIK3CA mutations in our study population. Further comprehensive investigations on this topic are needed to confirm our findings and to further understand the association between mutation status and SPLCs.
A phase I dose escalation study of weekly BI 836845, a fully human, affinity-optimized, insulin-like growth factor (IGF) ligand neutralizing antibody, in patients with advanced solid cancers.
Authors: Chia-Chi Lin, Kwang-Yu Chang, Dennis C Huang, Vicky Marriott, Ludy Van Beijsterveldt, Li-Tzong Chen, Ann-Lii Cheng
Journal: Journal of Clinical Oncology (2014)

2617 Background: The IGF signaling pathway has an important role in neoplasia and is associated with cancer progression, prognosis, and resistance to anti-cancer treatment. IGF-1 and IGF-2 are up-regulated in many tumors and exert multiple cellular activities through endocrine, autocrine, and/or paracrine manner. BI 836845 binds to and neutralizes the function of IGF-1 and IGF-2. The ligand-targeting approach differs from receptor-targeting by additional inhibition of IGF-2 signaling through IR-A. Objectives of this first-in-human trial were to assess the MTD or relevant biological dose (RBD), safety, PK, pharmacodynamics, and anti-tumor activity of weekly BI 836845 in cancer patients. Methods: In a 3+3 design, sequential cohorts of 3 to 6 patients (pts) with advanced or metastatic solid cancers refractory or not amenable to standard therapy received a weekly 1-hour intravenous infusion of BI 836845 following an AE-guided dose escalation. Treatment was continued in the absence of progressive disease and undue AE. The primary endpoints were DLT, MTD and/or RBD. Results: 48 pts, median age 57.5 (19-76) years were treated with BI 836845 at 14 dose levels (range: 10 to 1800 mg). Only one DLT, potentially drug-related grade 3 pulmonary hemorrhage originating from a tumor-adjacent vessel, was observed at 450 mg. The other of the two reported grade 3 drug-related AEs was lymphocyte decrease. No drug-related grade 4 or 5 AE was reported. Infusion-related reaction or drug-related hyperglycemia was not reported. MTD was not reached. BI 836845 showed a dose-proportional PK with a terminal half-life of about 6 days, a volume of distribution of 5.8 L, and a total plasma clearance of 0.5 mL/min. A RBD for further clinical development was selected at 1000 mg weekly. There were two confirmed PRs (nasopharyngeal carcinoma, at 800 mg; peripheral primitive neuroectodermal tumor, at 1050 mg) and 12 pts (25%) with confirmed SD. Conclusions: Weekly infusion of BI 836845 is well tolerated in cancer patients in the dose range tested without determination of a MTD. Preliminary anti-tumor activity has been observed. Clinical trial information: NCT01403974.
Phase II randomized study of dalantercept in combination with axitinib compared to axitinib alone as second-line treatment in patients with metastatic renal cell carcinoma.
Authors: Michael B. Atkins, Rupal Satish Bhatt, Martin Henner Voss, Brian I. Rini, Eric Jonasch, Elizabeth R. Plimack, Robert Alter, Rachel Barger, Dawn Wilson, Ty McClure, Ravi Kumar, Kenneth M. Attie, Matthew L. Sherman, Shuchi Sumant Pandya
Journal: Journal of Clinical Oncology (2013)

TPS4595 Background: The treatment of metastatic renal cell cancer (mRCC) with therapies targeting the vascular endothelial growth factor (VEGF) pathway delays disease progression; however, overcoming tumor resistance to these agents remains a therapeutic challenge. Activin receptor-like kinase 1(ALK1) is a type 1 receptor in the TGF-ß superfamily and is selectively expressed on activated endothelial cells. While VEGF drives the proliferative stage of angiogenesis, ALK1 is primarily involved in the maturation phase. Dalantercept is a human ALK1-Fc receptor fusion protein that binds to bone morphogenetic proteins (BMP) 9 and 10 (ligands for ALK1) and acts as a ligand trap. Preclinically, dalantercept showed delayed tumor growth in solid tumor models, including RCC models alone and in combination with sunitinib. In RCC models, the addition of dalantercept to sunitinib enhanced the reduction in tumor blood flow compared to sunitinib alone. Dalantercept showed anti-tumor activity in a completed phase 1 study in 37 pts. with advanced solid tumors. Based on this promising data, we hypothesize that ALK1 inhibition may be synergistic with axitinib, a VEGFR tyrosine kinase inhibitor (TKI), in pts. with mRCC. Methods: A two-part, multi-center, open label phase 2 study to evaluate safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of dalantercept plus axitinib as second line therapy is ongoing. In Part 1, dose escalation using a 3+3 design will assess the safety and PK of dalantercept SC every 3 weeks plus axitinib 5 mg PO BID until disease progression or unacceptable toxicity. Once the maximum tolerated dose (MTD) has been determined, up to 20 pts. may be enrolled in an expansion cohort to establish safety for the recommended dose for Part 2. Part 2 will include 112 pts. randomized 1:1 to dalantercept plus axitinib vs. axitinib alone. Key eligibility criteria are one prior TKI in the first-line setting, ECOG &lt;/= 1, and measurable disease. The primary efficacy endpoint is PFS. Secondary endpoints are OS, TTP, ORR, DOR, DCR, and PD biomarkers on archived tumor and serum specimens including BMP9/10 and ALK1 expression. Clinical trial information: NCT01727336.
Comparison of cisplatin induced nephrotoxicity with short hydration or conventional hydration in gastric cancer: A retrospective study.
Authors: Takeshi Aoyama, Hiroki Kato, Akane Hagino, Ryota Furutani, Kazuyuki Ito, Hidenori Yoshioka, Masashi Nakamura, Takashi Tunoda, Kazuyoshi Kawakami, Kenichi Suzuki, Takashi Ichimura, Kensei Yamaguchi, Toshihiro Hama
Journal: Journal of Clinical Oncology (2017)

211 Background: Cisplatin is administered in combination with massive and long term hydration to avoid renal toxicity. Although a short hydration protocol for cisplatin has been recently developed in lung cancer, which in gastric cancer has not been well clarified. We modified our XPT (capecitabine / cisplatin / trastuzumab) regimen, adopting short hydration method. This study was conducted to compare the preventive effect for renal toxicity of XPT therapy between the short hydration regimen and the conventional regimen. Methods: Medical records of patients with gastric cancer who received XPT therapy containing cisplatin at a dose of ≥ 80 mg/m 2 were reviewed for 3 cycles of the observational period. Patients received either the short hydration regimen or the conventional regimen; short hydration regimen consisted of 2200 - 2500 mL of hydration over a period of 6.2 hours with furosemide and magnesium supplementation on day 1 and 1050 mL of hydration over 4 hours on day2 and 3, and the conventional regimen consisted of 3200 - 3500 mL of hydration over 24 hours on day 1 and 1550 ml of hydration over 6 hours on day2 and 3. Renal toxicity was then compared between the two groups. Results: Out of the total 31 patients, 6 received the short hydration regimen and 25 received conventional regimen. An elevated serum creatinine level ≥ grade 1 was significantly less frequent in the group receiving the short hydration regimen (0%, 0/6) than in the group receiving the conventional regimen (48.0%, 12/25) ( P &lt; 0.05). The completion rate for the planned treatment in the short hydration group (100.0%, 6/6) was higher than that in the conventional hydration group (84.0%, 21/25). Conclusions: Based on the results of this study, short hydration may be a feasible regimen for XPT therapy in gastric cancer.
Comparision of predictive value between RECIST and maximum three dimensional Metabolic tumor burden assessed by 18F-FDG PET/CT in lung cancer.
Authors: Wenzhao Zhong, Qing-yi Hou, Qi-bin Chen, Xue-ning Yang, Ning Zhao, Hong-Hong Yan, Jinji Yang, Qing Zhou, Yi-Long Wu
Journal: Journal of Clinical Oncology (2015)

e19107 Background: Tumor burden is one of the most important prognostic factors for lung cancer. The aim of this study was to investigate the predictive significance of metabolic tumor burden (MTB) measured by 18F-FDG PET/CT compared with the traditional RECIST criteria in patients with lung cancer. Methods: Included in the study were 78 consecutive lung cancer patients who underwent 18F-FDG PET/CT examination before and after systemic treatment. Metabolic tumor burden in terms of metabolic tumor volume (MTV) and the maximum diameter (D), three size product (M) and 2 maximum diameter product (S) were determined, and compared for their performance in response rate (RR), and predicting overall survival (OS). Nonlinear model( ln(v/v0) = k1t+u1) assuming index X change with time in proportion was utilized. Results: The estimated Eviews output was ln(v/v0) = -0.005268t+e1 . The role of MTV change with time was V = v0 e-0.005268t ( 0.5268% decrease per day, p = 0.0000), compared with S = s3-0e-0.0023t ( 0.23% decrease per day, p = 0.0060) in the 2 maximum diameter of the product, and M = m0e-0.003935t ( 0.3953% decrease per day, p = 0.002) in three size product. The degree of model fitting for survival of D, M and MTV is R2 = 0.30537, R2 = 0.316024, and R2 = 0.396004, respectively. Conclusions: The ratio of change between MTV and time (v) is more significant compared with 2 maximum diameter product (S) and three size product(M) . MTV is the most sensitive predictor for RR and OS, and might serve as a surrogate marker for prediction of outcome in patients with lung cancer.
Predictors of outcome in patients with recurrent/metastatic head and neck squamous cell carcinomas (RMHNSCC) treated with weekly cetuximab and paclitaxel (CP).
Authors: Bruna Pellini Ferreira, Kelsey K. Baker, Mary Redman, Renato Martins, Keith D. Eaton, Laura Quan Man Chow, Christina S. Baik, Bernardo Goulart, Sylvia Mina Lee, Rafael Santana-Davila, Cristina P. Rodriguez
Journal: Journal of Clinical Oncology (2015)

e17065 Background: Patients (pts) with RMHNSCC commonly present with a poor PS that makes them inelegible to receive cisplatin based chemotherapy. Our group has adopted the CP regimen for RMHNSCC. We reviewed our experience to determine predictors for outcomes. Methods: We retrospectively identified RMHNSCC pts treated with weekly cetuximab (C) 400/250mg/m2 and paclitaxel (P) 80mg/m2. Patient demographics, tumor characteristics and treatment data were recorded. The Kaplan-Meier method was used to estimate survival, and multivariable Cox regression analysis was used to examine outcome predictors. Results: 59 pts received at least 1 cycle of CP between 1/2007 and 6/2014. Median age was 56 (range:39-80), 42(71%) were male and 43(75%) were white.Primary sites were as follows: hypopharynx 2(3%), skin/cutaneous 3(5%), larynx 11(19%), oral cavity 19(32%), oropharynx 22(37%), maxillary sinus 1(2%) and unknown 1(2%). 4(7%) had p16 positive oropharynx cancer.ECOG PS at CP initiation was 0 in 7(12%), 1 in 32(54%) 2 in 16(28%), 3 in 2(3%) and unknown in 2(3%) pts. 52(88%) had undergone prior curative therapy, 34 of the 52(63%) received platinum and 10(19%) cetuximab, concurrently with radiation. In 44(75%) CP was used as a first line regimen.Disease was locoregional only in 20 pts(34%), distant only in 15(25%), and both in 24(41%). The median number of cycles given was 5(range:1-29).Rash was reported in 34 pts (58%).Dose modifications were necessary in 27 pts(46%). The objective response rate was 47.5%: 27(45.8%) partial responses and 1(2%) complete response. 18(30%) pts had stable disease.With a median follow up of 5.5 months, median progression-free(PFS) and overall survival(OS) were 7.7 months (95%CI:5.5-8.9) and 13.2 months (95%CI:8.6-14.8), respectively. Using Cox multivariable analysis, an ECOG of 2/3 was associated with inferior OS(HR:3.94; p = 0.01; 95%CI:1.1-14.04) and PFS (HR:7.29; p < 0.01; 95%CI:2.1-26.0) compared to ECOG 0.First line CP admnistration was associated with superior PFS compared to second line(HR:2.6; p = 0.02; 95%CI:1.2-5.5). Conclusions: CP is feasible in RMHNSCC. First line use in ECOG 0/1 pts appears to confer superior outcomes.
Phase II study of neoadjuvant chemotherapy with a metronomic regimen of paclitaxel + cyclophosphamide + capecitabine followed by 5-fluorouracil + epirubicin + cyclophosphamide in operable triple-negative breast cancer (JBCRG-13 study).
Authors: Kenji Higaki, Norikazu Masuda, Toshimi Takano, Nobuki Matsunami, Takashi Morimoto, Shoichiro Ohtani, Makiko Mizutani, Takeshi Miyamoto, Katsumasa Kuroi, Shinji Ohno, Satoshi Morita, Masakazu Toi
Journal: Journal of Clinical Oncology (2013)

1048^ Background: Triple-negative breast cancer (TNBC) is generally associated with a poor prognosis. Combination therapy with anthracyclines and taxanes is widely used as preoperative systemic chemotherapy (PST), but pathological complete response (pCR) rate is ≤50%. We conducted metronomic PST in TNBC patients. Methods: Patients had primary breast cancer (T1C-3N0M0 or T1-3N1M0) with low ER expression (&lt;10%) diagnosed with either a triple-negative or HER2-negative invasive tumor. They received 4 cycles of a metronomic PCX regimen followed by 4 cycles of 5-fluorouracil (500 mg/m 2 , q3w) + epirubicin (100 mg/m 2 , q3w) + cyclophosphamide (500 mg/m 2 , q3w) (FEC regimen). The metronomic PCX regimen includes weekly administration of paclitaxel (80 mg/m 2 ; days 1, 8, 15), cyclophosphamide (50 mg/body; po, days 1-21) and capecitabine (1200 mg/m 2 ; po, daily), with one cycle set to 21 days. Primary endpoint was pCR rate. Results: Between March 2010 and September 2011, 41 patients were enrolled and 40 patients were treated. Characteristics of these 40 pts (ITT population) were: median age 52 years (range, 33-69), median tumor size 23.7 mm (range, 3.5-82), N(+) in 16 pts (40%), and estrogen receptor weakly positive (ER;1-9%) in 7 pts (17.5%). Median dose intensity for paclitaxel, cyclophosphamide and capecitabine was 89.7%, 92.1% and 89.8%, respectively. Five pts requested discontinuation of PST during PCX and 2 during FEC, primarily due to adverse events, leaving a per protocol population of 33 pts. pCR (ypT0/Tis ypN0) rate was 54.5% (18/33). 22 pts achieved CR, and ORR was 93.9% (95% CI, 79.8-99.3) as assessed by MRI or CT. Breast conservation rate was 72.7% (24/33), and 5 of 13 pts changed to partial resection from pre-planned total mastectomy. Grade 3-4 adverse events were neutropenia (35%), febrile neutropenia (25%), leucopenia (25%), and hand-foot syndrome (7.5%). There was no SAE report, and most pts completed treatment as outpatients. Conclusions: Metronomic PCX followed by FEC provided a high pCR rate and was manageable as PST in patients with TNBC. Clinical trial information: UMIN000003570.
Botulinum toxin as a biological weapon
Authors: Stephen S. Arnon, Robert Schechter, Thomas V. Inglesby, Donald A. Henderson, John G. Bartlett, Michael S. Ascher, Edward Eitzen, Anne D. Fine, Jerome Hauer, Marcelle Layton, Scott Lillibridge, Michael T Osterholm, Tara O'Toole, Gerald Parker, Trish M. Perl, Philip K. Russell, David L. Swerdlow, Kevin Tonat
Journal: JAMA (2001)

| FULL TEXT | PDF | MEDLINE 4. Biological and chemical terrorism: strategic plan for preparedness and response: recommendations of the CDC Strategic Planning Workgroup. MMWR Morb Mortal Wkly Rep 2000;49(RR-4):1-14. 5. Franz DR, Jahrling PB, Friedlander AM, et al. Clinical recognition and management of patients exposed to biological warfare agents. JAMA. 1997;278:399-411. MEDLINE 6. Gill MD. Bacterial toxins: a table of lethal amounts. Microbiol Rev. 1982;46:86-94. MEDLINE 7. National Institute of Occupational Safety and Health. Registry of Toxic Effects of Chemical Substances (R-TECS). Cincinnati, Ohio: National Institute of Occupational Safety and Health; 1996. 8. Montecucco C, ed. Clostridial neurotoxins: the molecular pathogenesis of tetanus and botulism. Curr Top Microbiol Immunol.