tbuckley/cabot-search huggingface dataset:
Correlation of menopausal status and age with outcome in breast cancer patients in the West of Ireland
Authors: M. G. Waldron-Lynch, D. McKeown, M. Keane
Journal: Journal of Clinical Oncology (2008)

22186 Background: Multiple risk factors for the occurrence of breast cancer have been documented. Worldwide, breast cancer diagnosed in pre-menopausal and thus, younger, women tends to display unfavourable characteristics and have a poorer survival outcome. Methods: This was a retrospective observational cohort study, comprising patients presenting to the oncology service the West of Ireland until 31st December 2006. Data was gathered by note search, recorded on a standardised questionnaire and included subjects' demographic, clinical and immunological data, including outcomes and survival. Univariate categorical data were analysed using Epi Info 2002 and the Chi-square test with Fisher's exact correction, and stratified Mantel-Haenszel chi-square as appropriate. Quantitative data were analysed using Student's t-test/ANOVA, or Mann-Whitney test for non-parametric data. Results: At diagnosis, there were similar proportions of pre- and post-menopausal women. Initial analysis suggests that menopausal status is not linked to outcome or risk of relapse. Most women presented early, at T1 and T2 (82%), N0 or N1 (84%), or M0 (92%). Most tumours were Grade 2. Those involved in a clinical trial had better outcomes (p=0.03), as were those ER+ (p=0.05), but less so PR+ (p=0.39) or HER2+ (p=0.48). Those with “Triple Negative” pathology (ER-, PR- and HER2-) tended to have a poorer prognosis (p=0.07). Stratifying for menopausal status reveals little difference, but this pilot sample size may be too small to pick up sensitive differences. Mean age at diagnosis was 55 years (median 51.5). There was no association between age at diagnosis and the likelihood of remission. Factors which had little impact on outcome included HRT, the Oral Contraceptive Pill and smoking. Discussion: In this population age and menopausal status were not linked to prognosis. Other established risk factors for the development of breast cancer such as the oral contraceptive pill, HRT and smoking had little influence on outcome. The extent to which each variable contributes to overall outcome will need to be examined more closely, using advanced regression techniques when all of the data are collected. No significant financial relationships to disclose.
Association Between Ischemic Stroke and Tumor Necrosis Factor Inhibitor Therapy in Patients With Rheumatoid Arthritis
Authors: Audrey S. L. Low, Mark Lunt, Louise K. Mercer, Kath D. Watson, William G. Dixon, Deborah P. M. Symmons, Kimme L. Hyrich
Journal: Arthritis & Rheumatology (2016)

Patients with rheumatoid arthritis (RA) are at an increased risk of ischemic stroke. Tumor necrosis factor inhibitors (TNFi) may influence risk and mortality after ischemic stroke by reducing inflammation. This study was undertaken to examine the association of TNFi with the risk of incident ischemic stroke and with 30-day and 1-year mortality after ischemic stroke.Patients with RA starting therapy with TNFi and a biologics-naive comparator group treated with synthetic disease-modifying antirheumatic drugs (DMARDs) only were recruited to the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis from 2001 to 2009. Patients were followed up via clinical and patient questionnaires as well as the national death register. Incident strokes were classified as ischemic if brain imaging reports suggested ischemia or if ischemic stroke was reported as the underlying cause of death on a death certificate. Patients with a previous stroke were excluded. Risk of ischemic stroke was compared between patients receiving synthetic DMARDs only and those ever-exposed to TNFi using a Cox proportional hazards regression model adjusted for potential confounders. Mortality after ischemic stroke was compared between synthetic DMARD-treated patients and TNFi-treated patients using logistic regression, adjusted for age and sex.To April 2010, 127 verified incident ischemic strokes (21 in 3,271 synthetic DMARD-treated patients and 106 in 11,642 TNFi-treated patients) occurred during 11,973 and 61,226 person-years of observation, respectively (incidence rate 175 versus 173 per 100,000 person-years). After adjustment for confounders, there was no association between ever-exposure to TNFi and ischemic stroke (hazard ratio 0.99 [95% confidence interval (95% CI) 0.54-1.81]). Mortality 30 days or 1 year after ischemic stroke was not associated with concurrent TNFi exposure (odds ratio 0.18 [95% CI 0.03-1.21] and 0.60 [95% CI 0.16-2.28], respectively).Exposure to TNFi does not appear to influence the occurrence of ischemic stroke in the medium term in patients with RA. The impact on mortality after ischemic stroke remains inconclusive.
Modulation of chemotherapy with para-amino benzoic acid (PABA): Translation from preclinical models to a completed phase I trial
Authors: A. C. Pavlick, L. Liebes, F. Muggia, E. Hardin, A. Morillo, S. Mendoza, D. Fry, P. Brooks
Journal: Journal of Clinical Oncology (2005)

7557 Background: B16F10 melanoma cells exposed to PABA resulted in pronounced depigmentation. In-vivo murine studies on B16F10 xenografts treated with daily PABA IP (50 mg/kg) and paclitaxel (P) showed that the PABA + P was significantly different from the control (p = 0.016) and P groups. Metastatic melanoma (mm) patients (pts) who fail first line therapy with DTIC receive platinums and/or taxanes as second line therapy. We conducted a Phase I trial of combination PABA, P and carboplatin(C) in mm pts who failed first-line therapy. Methods: C and PABA doses were fixed (AUC 5 mg/ml, IV; 2 g/d, po) with P escalated over 4 dose levels (100 -175 mg/m2). PABA was administered on days 1–10 with chemotherapy on day 6. 3 pts were enrolled at each dose level. Toxicity was assessed at day 21 of the 1st cycle. Correlative studies included PABA, P and C PK, shed collagen cryptic epitopes, and documentation of vitiligo. Results: 19 pts were enrolled, 18 eligible for assessment. 1 pt was enrolled, but progressed prior to treatment. All pts at DL I treated with only PABA and C showed no toxicities or response. For DL II and III, (P 100 and 125 mg/m2), no toxicities were seen. 3 of 6 pts showed clinical responses. The second pt on DL IV (P 150 mg/m2), developed Grade III neutropenia. DL IV was expanded to 6 pts. 5 additional pts had no toxicity. 2 of 6 pts on DL IV, had clinical responses (1 response lasting 10 cycles). All pts at DL V had no toxicity and 1 pt had a 50% reduction in palpable disease after one cycle. We observed inflammatory responses in responding cutaneous lesions. PABA PK for DL I-V showed a mean Cmax of 14 μg/ml ± 7.9 μg/ml at 0.5 hour, and an elimination HL that ranged from 0.2–13 h with a mean of 2 h. In the presence of T, the mean HL was 4.6 h. P effected PABA PK. In 7 out of 13 pts, a mean 3.4-fold increase of the AUC was observed 24 h following administration of P. Data on C AUC, shed cryptic epitopes, and histopathologic markers for antibodies to β1 integrin, BRCA-2 and CDC-25A are in progress. Conclusions: This regimen demonstrated activity with minimal toxicity in refractory melanoma pts. A phase II efficacy trial is planned. Supported by Chemotherapy Foundation and Cancer Innovations. No significant financial relationships to disclose.
Leukemoid reaction, bone marrow invasion, fever of unknown origin, and metastatic pattern in the natural history of advanced undifferentiated carcinoma of nasopharyngeal type: a review of 255 consecutive cases.
Authors: E Cvitkovic, M Bachouchi, H Boussen, P Busson, G Rousselet, R Mahjoubi, P Flores, T Tursz, J P Armand, N Azli
Journal: Journal of Clinical Oncology (1993)

This study is an analysis of frequency and relationship regarding two undifferentiated carcinoma of nasopharyngeal type (UCNT)-associated paraneoplastic syndromes (PNS): leukemoid reaction (LR) and fever of unknown origin (FUO) with bone marrow invasion (BMI) and metastatic pattern.A consecutive UCNT patient cohort (N = 255) with locally advanced (n = 142) or metastatic (n = 113) disease receiving chemotherapy alone or in combination with radiotherapy was studied. All patients had a complete baseline work-up that included bone marrow biopsy.UCNT has distinctive features among head and neck squamous cell cancers (HNSCC). These include early subclinical dissemination, with 70% of metastases appearing within 18 months of first symptoms. Metastases are common in bone (65% v 25% in HNSCC), liver (29% v 23%), and lung (18% v 84%), and BMI is observed in 25% of UCNT patients with metastases. Metastases likelihood is related to lymph node involvement, with 64% of patients with metastases having N3 disease. Involved lymph nodes in contrasted CT scans revealed hypodensity in 26% of UCNT patients versus 79% in patients with other HNSCC. Hypercalcemia was observed in one case. LR was identified in 41 patients (16%); in 26 of the 41 patients (64%) it was observed concomitant with N3 and/or metastatic disease. FUO was found in 23 patients (9%) and was associated in four instances with BMI and in 17 with LR (in four instances with both). Brain metastases or meningeal carcinomatosis were not observed despite the high rate of skull base compromise. Paraneoplastic signs were observed in 47 of 255 cases (18.5%) and were more frequent in patients with metastases. However, PNS were observed in 15 patients with negative metastases work-up.The PNS described could help in the diagnosis and follow-up of UCNT patients because they may be the first manifestation of the disease or may reappear with relapse. BMI is a frequent finding in patients with metastases and is unrelated to PNS.
Enrolling a rare patient population: Establishing proof of concept for FP-1039, an FGF “trap,” in endometrial cancer patients with the S252W FGFR2 mutation.
Authors: H. N. Keer, T. C. Harding, W. M. Kavanaugh
Journal: Journal of Clinical Oncology (2010)

TPS260 Background: Advanced endometrial cancer remains an uncommon but clinically significant problem because available therapies are inadequate. Recent data suggest that a subset of patients with endometrial cancer (∼7% of all cases) possess a point mutation (S252W) in the extracellular domain of the fibroblast growth factor receptor 2 (FGFR2). Tumors driven by this mutation should be highly responsive to ligand sequestration by FP-1039, an FGFR1:Fc fusion protein currently in phase I trials. Preclinical data demonstrate that endometrial tumors bearing the S252W FGFR2 mutation are more sensitive to FP-1039 than tumors bearing wild-type FGFR2. Clinically testing this hypothesis requires screening for an infrequent mutation in a small patient population, which is challenging to do in a timely and economic manner. Here we present an approach to a proof-of-concept trial in this setting. Methods: The trial is divided into 2 parts: a screening trial (1) and a treatment trial (2). 1) A laboratory test using a CLIA-certified central lab is established for determination of tumor mutation status of potential patients. It is estimated approximately 170 subjects will need to be screened to enroll 7 subjects for treatment. Through contact with their gynecologic oncologists, general oncologists, social networking websites, or other communication means, potential patients are encouraged to have a sample of original tumor sent for analysis. 2) In a single-stage phase II design, up to10 patients will be enrolled and treated with weekly FP-1039 until progressive disease. Eligibility criteria will include recurrent or advanced endometrial cancer with 0 or 1 prior systemic therapies, acceptable performance status and organ function, and the presence of the S252W FGFR2 tumor mutation. Safety will be assessed by physical exams and laboratory evaluations. Disease will be assessed by serial CT exams approximately every 2 months. The primary endpoint will be objective response rate; progression-free survival at 6-months will also be assessed. Conclusions: S252W mutant-endometrial cancer provides a challenging opportunity to demonstrate proof-of-concept for an FGF-trap molecule. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration FivePrime Therapeutics FivePrime Therapeutics
Phase I study of panitumumab, chemotherapy and intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC): Early results
Authors: L. J. Wirth, M. R. Posner, R. B. TIshler, R. I. Haddad, L. Goguen, J. R. Clark, A. M. Allen
Journal: Journal of Clinical Oncology (2007)

6083 Background: Both chemotherapy and epidermal growth factor receptor (EGFR) antibody therapy improve outcomes in HNC when added to radiotherapy. This phase I study investigates the addition of the fully human anti-EGFR antibody, panitumumab, to chemoradiotherapy (CRT) for HNC. Methods: Treatment naïve adults with stage III/IV HNC (primary sites include oropharynx and unknown primary) with normal hematologic, renal, and liver function are currently enrolling in a 2-part study. Part A determines the maximum tolerated dose (MTD) of paclitaxel in 2 dose levels (DLs) (15 and 30 mg/m 2 wkly×7 wks) with fixed-dose carboplatin and panitumumab (AUC of 1.5 and 2.5 mg/kg wkly, respectively) plus IMRT (70 Gy). Patients (pts) are enrolled in sets of 3. Part B determines the MTD of 5-FU in 2 DLs (800 and 900 mg/m 2 days 1–4, Q21d) with fixed-dose docetaxel, cisplatin and panitumumab (75 mg/m 2 , 100 mg/m 2 and 9 mg/kg, Q21d, respectively) for 3 cycles followed by panitumumab + CRT, as determined in Part A. Results: To date, 8 pts (n=3 at DL 1, n=5 at DL 2) have enrolled in Part A. One dose-limiting toxicity has occurred in DL 2: grade (gr) 4 febrile neutropenia. Other adverse events include gr 3/4 mucositis (n=6), gr 3/4 radiation dermatitis (n=6), gr 2 acneiform rash (n=6), gr 3 dysphagia (n=6) and gr 2 oral pain (n=6). Dose-reduction has not been necessary thus far. Enrollment will continue in a cohort of 10 pts in DL 2. Of 4 pts evaluated for response, 4 had complete response in the primary and neck, and 1 had a residual neck mass. This pt had 1 positive node on neck dissection. Conclusions: Preliminary results suggest that panitumumab can be added to CRT for treatment of HNC without magnifying the expected toxicities with CRT. Part B will investigate panitumumab + sequential therapy for HNC once the MTD of Part A is established. No significant financial relationships to disclose.
Ginger for chemotherapy-related nausea in cancer patients: A URCC CCOP randomized, double-blind, placebo-controlled clinical trial of 644 cancer patients
Authors: J. L. Ryan, C. Heckler, S. R. Dakhil, J. Kirshner, P. J. Flynn, J. T. Hickok, G. R. Morrow
Journal: Journal of Clinical Oncology (2009)

9511 Background: Despite the widespread use of antiemetics, post-chemotherapy nausea and vomiting continue to be reported by up to 70% of patients receiving chemotherapy. Ginger (Zingiber Officinale), an ancient spice, is used by practitioners worldwide to treat nausea and vomiting. We conducted a multi-site, phase II/III randomized, placebo-controlled, double-blind clinical trial to assess the efficacy of ginger for chemotherapy-related nausea in cancer patients at the University of Rochester-affiliated Community Clinical Oncology Program (CCOP) member sites. Methods: Cancer patients who experienced nausea following any chemotherapy cycle and were scheduled to receive at least three additional cycles were eligible. Patients were randomized into four arms: 1) placebo, 2) 0.5g ginger, 3) 1.0g ginger, or 4) 1.5g ginger. All patients received 5-HT 3 receptor antagonist antiemetics on Day 1 of all cycles and took three 250mg capsules of ginger or placebo twice daily for six days starting three days before the first day of the next two cycles. Patients reported the severity of nausea during the morning, afternoon, evening, and night on a 7-point semantic rating scale (‘1' = ‘Not at all Nauseated' and ‘7' = “Extremely Nauseated”) for Days 1–4 of each cycle. The goal was to determine if ginger was more effective than placebo in controlling chemotherapy-related nausea in participants given a 5-HT 3 receptor antagonist antiemetic. Results: A total of 644 patients were accrued (90% female, mean age = 53). Breast (66%), alimentary (6.5%), and lung (6.1%) cancers were the most common cancer types. Analysis of covariance (ANCOVA) examined change in nausea in the four study arms on Day 1 of cycles 2 and 3. All doses of ginger significantly reduced nausea (p=0.003). The largest reduction in nausea occurred with 0.5g and 1.0g of ginger. Also, time of day had a significant effect on nausea (p&lt;0.001) with a linear decrease over 24 hours for patients using ginger. Conclusions: Ginger supplementation at daily dose of 0.5g-1.0g significantly aids in reduction of nausea during the first day of chemotherapy. Supported by NCI PHS grants 1R25CA10618 and U10CA37420. No significant financial relationships to disclose.
Abstract 12392: When Essential Hypertension is Combined With Visceral Adiposity There is Discordance Between Arterial Stiffness and Peripheral Wave Reflections
Authors: Vasiliki Katsi, George Souretis, Stylianos Veioglanis, Dimitrios Tousoulis, Christodoulos Stefanadis, Ioannis Kallikazaros
Journal: Circulation (2012)
Sequential Biochemical Modulation of Fluorouracil With Folinic Acid, N-Phosphonacetyl-L-Aspartic Acid, and Interferon Alfa-2a in Advanced Colorectal Cancer
Authors: Melanie E Royce, William McGarry, Beth Bready, Shaker R. Dakhil, Robert J. Belt, J. Wendall Goodwin, Richard Gray, Paulo M. Hoff, Rodger Winn, Richard Pazdur
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Several agents have been evaluated for their effect as biochemical modulators of fluorouracil (5-FU) in the treatment of metastatic colorectal carcinoma. In this study, we used folinic acid (FA), N-phosphonacetyl-L-aspartic acid (PALA), and recombinant interferon alfa-2a (IFNα-2a) in a sequential order to assess the efficacy of this approach in patients with metastatic colorectal carcinoma. PATIENTS AND METHODS: Forty-four patients with metastatic colorectal carcinoma were enrolled onto the study. The treatment course consisted of three cycles: (cycle 1) FA 20 mg/m 2 followed by 5-FU 425 mg/m 2 on days 1 to 5; (cycle 2) PALA 250 mg/m 2 on days 29, 36, 43, and 50 and 5-FU 2,600 mg/m 2 as a 24-hour infusion on days 30, 37, 44, and 51; and (cycle 3) IFNα-2a 9 million units (MU) three times a week for 5 weeks beginning on day 57, with a continuous infusion of 5-FU 750 mg/m 2 on days 57 to 61, and then weekly bolus of 5-FU 750mg/m 2 /wk on days 71, 78, and 85. Response was determined after cycle 3. RESULTS: All patients had a Zubrod performance status ≥ 2, measurable disease, and had received no prior chemotherapy for their metastatic disease. A total of 212 cycles were given. Thirty-six patients were assessable for response. No complete responses were seen. Seven patients had a partial response, eight had stable disease, and 15 had progressive disease. The median duration of response was 25 weeks, and the median survival was 53 weeks. Grade 3 and 4 toxic effects included granulocytopenia, stomatitis, diarrhea, rash, nausea, and fatigue. CONCLUSION: This trial provided no evidence that sequential biochemical modulation of 5-FU in patients with metastatic colorectal carcinoma had any therapeutic advantage over conventional treatment regimens of 5-FU plus FA.
EGFR Mutation Impact on Definitive Concurrent Chemoradiation Therapy for Inoperable Stage III Adenocarcinoma
Authors: Kosuke Tanaka, Toyoaki Hida, Yuko Oya, Tomoyo Oguri, Tatsuya Yoshida, Junichi Shimizu, Yoshitsugu Horio, Akito Hata, Reiko Kaji, Shiro Fujita, Yoshitaka Sekido, Takeshi Kodaira, Masaki Kokubo, Nobuyuki Katakami, Yasushi Yatabe
Journal: Journal of Thoracic Oncology (2015)
Randomized phase II trial on primary chemotherapy with high-dose methotrexate (HD-MTX) alone or associated with high-dose cytarabine (HD-araC) for patients with primary CNS lymphoma (I.E.L.S.G. #20 Trial): Tolerability, activity, and survival analyses
Authors: A. J. Ferreri, M. Reni, M. Martelli, G. Pangalis, M. Frezzato, G. Cabras, A. Fabbri, G. Corazzelli, E. Zucca, F. Cavalli
Journal: Journal of Clinical Oncology (2009)

8545 Background: HD-MTX-based chemotherapy (cht) is the conventional approach to primary CNS lymphoma (PCNSL), but superiority of polycht over HD-MTX alone is unproven. A benefit of adding HD-araC to MTX has been suggested. This is a randomized phase II trial comparing HD-MTX monocht versus HD-MTX plus HD-araC as primary cht in immunocompetent patients (pts) with PCNSL. Methods: 79 HIV- pts with newly diagnosed PCNSL, age 18–75 ys, ECOG-PS≤3, and measurable disease were randomly assigned to receive 4 courses (interval 3 weeks) of MTX 3.5 g/mq (control arm; n=40) or MTX (same dose) + araC 2 g/mq × 2/d, d 2–3 (experimental arm; n=39). Cht was followed by whole-brain irradiation. Pts were stratified based on IELSG score and centre irradiation policy for pts &gt;60 ys in complete remission (CR) after cht. CR rate (CRR) after cht was the primary endpoint; planned accrual (α=.05 β=.2) for P0 30% and P1 50% was 39 pts/arm. Results: Median age of the 79 entered pts was 58 ys (range 25–74). No differences in clinical presentation between arms were observed. Two hundred thirty-one (73%) of the 316 planned courses were actually delivered (MTX 71%; MTX+araC 76%). Causes of cht interruption were: progressive disease in 20 MTX and 8 MTX+araC pts, toxicity in 1 MTX and 7 MTX+araC pts and refusal in 2 MTX+araC pts. As expected, neutropenia, thrombocytopenia and infections were more common in MTX+araC arm. All G3–4 non-hematological toxicities were &lt;5%. One MTX pt and 3 MTX+araC pts died of toxicity. CRR was 18% after MTX and 46% after MTX+araC (p=0.006), with an ORR of 40% and 69% (p=0.009), respectively. At a median follow-up of 30 m., 31 MTX and 22 MTX+araC pts experienced failure, with a 3-yr FFS of 21±6% and 38±8% (p=0.01), respectively. No differences in relapse sites or salvage efficacy between treatment arms were observed. Twelve MTX and 20 MTX+araC pts are alive, with a 3-yr OS of 32±8% and 46±9% (p=0.07). Conclusions: This is the first randomized trial on PCNSL with completed accrual. The addition of HD-araC to HD-MTX resulted in significantly better outcome and acceptable toxicity. MTX+araC may be the cht combination used as control arm in future randomized trials. No significant financial relationships to disclose.
MVAC for bladder cancer: time to move forward again.
Authors: E G Levine, D Raghavan
Journal: Journal of Clinical Oncology (1993)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1993.11.3.387 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8445412 MVAC for bladder cancer: time to move forward again. E G LevinexE G LevineSearch for articles by this author , D RaghavanxD RaghavanSearch for articles by this author https://doi.org/10.1200/JCO.1993.11.3.387 First Page PDF © 1993 by American Society of Clinical Oncology