tbuckley/cabot-search huggingface dataset:
Trial of Amino-Oxyacetic Acid: An Anticonvulsant
Authors: J A TIBBLES, D A McGREAL
Journal: JAMA (1963)

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Oral combination chemotherapy for refractory/relapsed lymphoma with the PEP-C (C3) regimen (daily prednisone, etoposide, procarbazine, cyclophosphamide): Low-dose continuous metronomic multidrug therapy
Authors: M. Coleman, J. Ruan, R. R. Furman, R. Niesvizky, P. Martin, J. P. Leonard
Journal: Journal of Clinical Oncology (2007)

8064 Background: Oral daily low dose chemotherapy (metronomic therapy) may maintain continuous sequential drug levels to impact endothelial cell viability (anti-angiogenesis) or to overcome drug resistance. Methods: We retrospectively reviewed data on 97 patients with refractory/relapsed Hodgkin's and non-Hodgkin's lymphoma treated with the PEP-C (C3) regimen, which consists of oral prednisone (20 mg in am), cyclophosphamide (50 mg at noon), etoposide (50 mg at dinner) and procarbazine (50 mg at h.s.with an oral anti- emetic). Medications were administered daily until the white blood cell count fell to less than 3000/dl, when treatment was held until recovery from the nadir. Treatment was then reinstituted on a daily, alternate day, or fractionated weekly basis (e.g. 5 of 7 days) based on patient tolerance. Doses given per day were constant. Results: All patients had been previously treated, with 80% having received 2 or more prior therapies and 57% with 3 or more previous regimens. Overall, 69 patients (71%) achieved a response. Responses by histology were: follicular (n=26) 92%, mantle cell (n=22) 82%, marginal zone (n=14) 71%, small lymphocytic (n=12) 67%, Hodgkin's lymphoma (n=9) 44%, diffuse large B cell (n=9) 33%, and T cell (n=5) 40%. Time on therapy of responding patients ranged from 3 weeks to 48 months (median 9 months, mean 11 months). Toxicity was predominantly myelosuppression, with hospitalization for infection occurring in 10 patients. Five patients developed H. zoster. Gastrointestinal effects prompting cessation of therapy occurred in 6 subjects, and 2 patients developed hematuria. Conclusions: Low dose, continuous (metronomic) combination chemotherapy with PEP-C is an easily administered, generally well- tolerated and effective treatment for relapsed/refractory lymphoma, particularly in indolent and mantle cell histologies. No significant financial relationships to disclose.
Molecular Mapping of the Chloride Binding Site in von Willebrand Factor (VWF): Energetics and Conformational Effects on the ADAMTS-13 Interaction with Wild Type and Type 2B R1306W VWF Forms.
Authors: Raimondo De Cristofaro, Flora Peyvandi, Luciano Baronciani, Roberta Palla, Silvia Lavoretano, Rossana Lombardi, Enrico Di Stasio, Augusto B. Federici, Pier Mannuccio Mannucci
Journal: Blood (2006)
A randomized double blind phase I-II study to determine the tolerability/efficacy of two different doses of lenalidomide (L), CC- 5013, in biochemically relapsed (BR) prostate cancer (PC) patients (pts) (M<sub>0</sub>) after local treatment (LT)
Authors: V. J. Sinibaldi, M. A. Carducci, S. Moore-Cooper, B. George, S. Denmeade, C. G. Drake, J. Walczak, R. Pili, M. L. Zahurak, M. A. Eisenberger
Journal: Journal of Clinical Oncology (2009)

5130 Background: BR following LT is common in PC with no defined standard treatment. Lenalidomide (L) is an immunomodulatory agent with anti-angiogenic and direct antitumor effects. Methods: This trial was designed to evaluate a dose-effect relationship of L in BR PC. Pts were randomized to either 5 or 25 mg/day(d), PO, d 1–21 (28-d cycles); then stratified by PSADT (&lt; 3, 3–8.9, ≥ 9 mos), LT and prior ADT. Eligible pts had: rising PSA (≥1 ng/mL), M 0 disease, testosterone &gt; 150 ng/mL, adequate bone marrow, renal, and hepatic function. Baseline and Q 2 mos PSA's were processed after Q 6 mos of L, along with CT and bone scan. Toxicity exams were Q mo. Primary endpoints are safety and progression after 6 mo of L (defined by a confirmed ↑ in PSA &gt; 25% over the baseline value or mets). Secondary endpoints are changes of slopes in PSA related to pharmacokinetics (pk). A sample size of 30 pts/arm provides an 85% power to detect a PSA progression rate of 40% (compared to 80% predicted ) with a Type I error = 0.05 (Fishers exact test). Results: 59 pts were entered July 20, 2006-December 31, 2008. Pooled data from the 2 arms: median: age 64 (50–81), ECOG PS 0, baseline PSA 9.3 ng/ml (1.3–92.8 ng/ml). 16 pts had PSADT &lt;3 mos, 26 from 3–8.9 mos, and 17 ≥ 9 mos. Median: F/U on all 59 pts is 351 + d (9 + -887 + d); # cycles = 6 (1–30). Thus far, 44/59 pts completed 6 cycles of L (1 had PD, 6 stopped L due to toxicity, 8 too early). 22 /44 who completed 6 mos of L remained on L &gt; 6 mos ( 7 + -30 + mos); including 7 pts ≥ 24 mos. Of 44 pts, blinded evaluation of PSA's at 6 mos: 4 pts had ≥ 50% ↓, 22 had stable PSA,17 had PD, 1 too early . Rash was DLT. Other Gr toxicities: appendicitis, abd pain, neck pain, venous thrombolic disease, fatigue, pruritus. Conclusions: Preliminary data prior to unblinding the study treatment arms, from pooled data, suggest that L may be administered &gt; 6 mos with acceptable toxicity, and is associated with PSA declines and long term stabilization in pts with BR. Supported by a grant from Celgene Corporation. Data coordination infrastructure is supported by the Prostate Cancer Foundation and The James Stine research fund. [Table: see text]
First line infusion of 5-fluorouracil, leucovorin and oxaliplatin for metastatic colorectal cancer : 4-day chronomodulated (FFL4–10) versus 2-day FOLFOX2. A multicenter randomized Phase III trial of the Chronotherapy Group of the European Organization for Research and Treatment of Cancer (EORTC 05963)
Authors: S. Giacchetti, G. Bjarnason, C. Garufi, N. Tubiana-Mathieu, S. Iacobelli, L. Dogliotti, R. Smaaland, C. Focan, B. Coudert, F. Lévi
Journal: Journal of Clinical Oncology (2004)

3526 Background: The tolerability and anticancer activity of a 5-day (d) infusion of 5-fluorouracil (FU), leucovorin (LV) and oxaliplatin (l-OHP) were improved with chronomodulated (CM) delivery as compared with constant rate infusion in metastatic colorectal cancer (MCC) (Lévi, Lancet Oncology, 2, 2001). We investigated whether FFL4–10 - schedule (sch) B - (Berthault et al. JCO 1996) improves survival as compared with FOLFOX2 - sch A - (De Gramont et al. EJC 1997) in MCC patients (pts). Methods:554 pts had to be randomized to receive either sch at the same dose levels (g/m2) per course (c) q14 d: FU (c1, 3; c2, 3.4; c3 : 3.6; LV, 1.2; l-OHP, 0.1 . For sch A, l-OHP was infused for 2 h at daytime ( d1), LV for 2 h (d1, d2) and FU for 22 h (d1, d2). For sch B, FU-LV and l-OHP were infused daily from 10 pm to 10 am (peak at 4 am) and from 10 am to 10 pm (peak at 4 pm) using a programmable pump. Pts were evaluated q14 d for toxicity and q4 c for response. The primary endpoint was Overall Survival (OS), 430 events being required. Results: 564 pts (sch A/B : 282/282 pts) from 36 centers with median follow-up >3 years; sch A/B %pts: women, 40.1/40.4; Colon primary, 59.9/58.5; PS 0/1/2, 49.3/40.4/9.2 vs 47.5/40.4/11.7; single M site, 50.7/50; synchronous M, 73/74.1; adjuvant chemo, 16.7/19.1. N of courses : sch A/B: 2916/2783. Toxic deaths : 1/2. OS (Hazard Ratio=0.94, 95% CI:0.73–1.21) and Progression Free Survival (PFS) (HR=1.01, 95% CI: 0.81–1.26) did not differ significantly. Conclusions: This is the first trial that has compared the two most active treatment schedules as 1st line chemotherapy of MCC. No difference in OS and PFS were observed with a median survival > 18 months in both regimens and a different but low toxicity profile (<7 % of courses). Supported in part by an educational grant from SANOFI-SYNTHELABO. No significant financial relationships to disclose.
A pilot study: Combined treatment of docetaxel with 3-D conformal radiation therapy followed by docetaxel consolidation chemotherapy for men with intermediate/high-risk prostate cancer (IHPC)
Authors: R. L. Xu, H. L. Adler, P. Hentschel, K. Rauso, R. A. Munkelwitz, S. Madajewicz, T. Park
Journal: Journal of Clinical Oncology (2005)

4795 Background: More than 1/3 of the patients (pts) with clinically localized IHPC will relapse from their diseases after receiving initial treatment. This pilot study is to evaluate feasibility and tolerability of the combined chemoradiotherapy (CRT) and adjuvant chemo-consolidation (ACC) using Docetaxel in an attempt to reduce the rate of disease recurrence. Methods: 15 men with histologically confirmed localized adenocarcinoma of the prostate are to be enrolled in this trial. Eligible pts must have either (1) Intermediate-risk features (any two of the following: PSA 10–20 ng/ml; Gleason score 7; T2b, T2c, or T1c≥2/6 or 4/12 positive cores) or (2) High-risk features (PSA ≥ 20 ng/ml; Gleason score ≥ 8 or T3). The pts receive Docetaxel 20 mg/m2 iv at Week (W) 1, 2, 3, 4, 5 plus conformal pelvic radiation (4500 cGy, W1–5) and prostate boost (2700 cGy EBRT OR Brachythrapy, W6–8), followed by ACC with Docetaxel at 35 mg/m2 iv weekly starting at W13 given 3 of 4 weeks for 4 cycles. Results: Five pts were enrolled since 6/2004 (3 currently evaluable): the median age of 76 (range 68–80), mean PSA of 11.27 ng/ml (4.84–23) and the median Gleason score of 8 (7–9). Mean PSA decrease was 59% (75,75,26) and 92% (89,95) before the 1st ACC and 2nd ACC cycle (not androgen-deprived), respectively. Therapy was well tolerated: no grade (G) 4 or unexpected toxicities detected. Observed clinical and laboratory abnormalities include G1–2 fatigue (G1, 1/3 and G2, 1/3 pts)/proctitis (G1, 2/3 and G2, 1/3 pts) and G1 anemia (2/3 pts)/hyperglycemia (2/3 pts), respectively. There was one episode of afebrile, spontaneously resolved neutropenia (G2) without subsequent treatment delay. Abnormal liver function tests (LFT: ALT-G3, AST-G2 and TB-G1) were detected in 1/5 pts after the initial dose of chemotherapy. Repeat LFTs on the following day and thereafter were normal. Conclusions: This exploratory trial of the combined CRT and ACC for the pts with the IHPC appeared to be well tolerated and clinically feasible without causing a delay to deliver radiotherapy. Support: Aventis Pharmaceuticals, Inc. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
An open-label, balanced, 2-period crossover study to investigate the influence of aprepitant on docetaxel pharmacokinetics
Authors: K. Hande, P. Nygren, M. Fedgchin, K. Vandyck, A. Majumdar, D. Panebianco, K. Petty, M. Sjolund, V. Cocquyt, S. Vanbelle
Journal: Journal of Clinical Oncology (2004)

2094 Background: Several cancer chemotherapeutic agents are metabolized by CYP3A4. Co-administration of compounds that inhibit CYP3A4 may lead to decreased metabolic clearance, increased exposure, and increased toxicity of these antineoplastic agents. Aprepitant (EMEND), a recently approved antiemetic agent, moderately inhibits human CYP3A4 in vivo and in vitro (Ki of ∼10 uM). To determine if aprepitant affects the pharmacokinetics of chemotherapeutic agents metabolized by CYP3A4, this study examined the effect of aprepitant on docetaxel, which is cleared largely by CYP3A4 metabolism. Methods: Ten patients at 3 investigative sites were given the same dose of docetaxel (DOC) monotherapy (60 to 100 mg/m2) on two separate occasions (∼3 weeks apart). In one of the cycles, patients received aprepitant (APR) 125 mg PO 1 hour prior to docetaxel infusion, followed on Days 2 and 3 with a single oral aprepitant dose of 80 mg. On the alternate treatment, they received docetaxel alone. The pharmacokinetic profile of docetaxel was determined for 30 hours following docetaxel infusion in both periods. Results: The pharmacokinetic parameters of docetaxel are summarized in the table below. Docetaxel pharmacokinetics were not affected by coadministration of aprepitant. No difference in toxicity was noted in the two chemotherapy cycles: mean absolute neutrophil count nadirs were 0.96 x 109/L with aprepitant and 0.85 x 109/L without aprepitant. Conclusions: Aprepitant has no effect on docetaxel pharmacokinetics or toxicity. Moderate inhibitors of CYP3A4 metabolism such as aprepitant are unlikely to have significant clinical effects on chemotherapeutic agents metabolized by CYP3A4. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck & Co., Inc. Merck & Co., Inc. Merck & Co., Inc. Merck & Co., Inc. Merck & Co., Inc.
Physical and psychological well-being in patients with stage IV GI cancer
Authors: G. M. Rodin, J. Jones, A. Rydall, M. Moore, L. Gagliese
Journal: Journal of Clinical Oncology (2004)

8266 Background: In many cancer centres, referral to palliative care often does not occur until near the end of life, despite substantial disease burden much earlier in the course of the illness. The present longitudinal study is being conducted to evaluate disease burden and its relation to psychological well being in patients with stage IV cancer receiving treatment at a comprehensive cancer center. Methods: Patients with stage IV gastrointestinal (GI) cancer are being recruited to this study from outpatient clinics at Princess Margaret Hospital, Toronto, Canada. Subjects who pass a cognitive screen (Short Orientation-Memory-Concentration Test ≥ 20) are administered self-report measures at 1–2 monthly intervals. These include: The Brief Pain Inventory, The Memorial Symptom Assessment Scale, The Beck Depression Inventory–II, The Beck Hopelessness Scale, The Schedule of Attitudes Towards Hastened Death, The Functional Assessment of Chronic Illness Therapy-Sp-12, and The Rosenberg Self-Esteem Scale. Results: Amongst 115 subjects with stage IV GI cancer recruited thus far (72% participation rate), multiple physical symptoms were common (\(\underline{\mathrm{M}}\)=5.0 ±3.7), including moderate to severe fatigue (52.2%), sleep disturbance (47.8%) and pain (46.1%). Psychological disturbances were also common, including moderate to severe depressive symptoms (20.9%), and hopelessness (26.1%). Pain, the number of physical symptoms, gender, self-reported spirituality and self-esteem together accounted for 53% of the variance in predicting depression (p<.01). Conclusions: Multiple physical symptoms, including significant pain, are common in patients with stage IV GI cancer, and these symptoms are associated with an increased risk of depression. Trials of early multidimensional palliative interventions are needed to determine to what extent these disturbances can be alleviated and quality of life can be improved in patients with stage IV disease. No significant financial relationships to disclose.
Bilateral breast cancer: One or two entities?
Authors: M. Mandarà, A. Caldara, M. Pavarana, A. Auriemma, E. Fiorio, M. Frisinghelli, A. Mercanti, R. Sabbioni, G. L. Cetto, A. Molino
Journal: Journal of Clinical Oncology (2005)

823 Background: Bilateral breast cancer affects about 5% of previously treated breast cancer patients, and may be synchronous (both tumours present at the time of diagnosis) or metachronous (two cancers occurring at different times). The aim of this study was to compare the characteristics of the first and contralateral tumours. Methods: The 5122 women with invasive operable breast cancer attending the University and Civic Hospitals of Verona between January 1992 and March 2004 included 198 (3.8%) with contralateral breast cancer: 102 (2%) with metachronous and 96 (1.8%) with synchronous tumours. The chi-squared test was used to analyse the characteristics of the first and contralateral tumour. Results: The first tumours were Tis in 13.4% of the cases (52.9% T1, 23% T2, 2.1% T3 and 7.5% T4), as against 21.9% of the contralateral tumours (56.1% T1, 13.4% T2, 1.6% T3 and 4.3% T4) (p<0.001); 11% of the first tumours were G1, 52.5% G2 and 35.6% G3, whereas 22.8% of the second tumours were G1, 43.6% G2 and 33.7% G3 (p<0.001); 44.8% of the first and 26.7% of the contralateral tumours showed node involvement (p<0.01); 82.1% vs 79.9% were ER+ (p<0.01) and 56.6% vs 50.4% PGR+ (p<0.001); Ki-67 levels were low (0–15%) in 62% vs 66.9%, intermediate (16–25%) in 20.5% vs 15.7%, and high (26–100%) in 17.3% vs 17.3% (p<0.001); C-erb-b2 was overexpressed in 40.6% vs 31.3% (p=0.06); and bcl-2 in 88.9% vs 55.6% (p=0.9). Conclusions: Our results show that second tumours are less aggressive than first tumours, which suggests that the two tumours may have different origins. No significant financial relationships to disclose.
Tumor necrosis factor-α is a potent endogenous mutagen that promotes cellular transformation
Authors: B. Yan, H. Wang, Z. N. Rabbani, M. W. Dewhirst, C. Li
Journal: Journal of Clinical Oncology (2007)

21104 Background: It is estimated that chronic inflammation is an important underlying condition for sporadic human tumor development, accounting for approximately 20% of human cancers. TNFa is an inflammation cytokine playing an important role in inflammation- associated cancers. However, the underlying mechanism of how TNFa leads to cancer is not clear. Before we initiated this study, TNFa is not known to have a direct effect on DNA. Methods: We studied genetic mutations, cellular transformation in cells and mice treated with TNFa. DNA damages and genetic aberrations caused by TNFa treatment were measured by gene amplification assay, micronucleus assay, cytogenetic analysis for chromosomal aberrations and immunostaining of 8-OHdG (8-hydroxydeoxyguanine; marker for DNA damage and oxidative stress). Cellular transformation was studied by standard transformation assay using mouse embryo fibroblast cells. Results: In this study, we found that TNFa can cause DNA damages through induction of reactive oxygen species (ROS). Our findings include: (1) The mutagenic effect of TNFa is comparable to that of ionizing radiation. TNFa treatment in cultured cells resulted in increased gene amplification, micronuclei formation and chromosomal instability. (2) Antioxidants significantly reduced TNFa-induced genetic mutations. (3) TNFa also induced oxidative stress and nucleotide damages in mouse tissues in vivo. (4) Moreover, TNFa treatment alone led to increased malignant transformation of mouse embryo fibroblasts, which could be partially suppressed by antioxidants. (5) The mutagenic effect of TNFa is independent that of NF?B which was shown to be a mediator in inflammation-associated cancers. Conclusions: As TNFa is known to be involved in chronic inflammatory diseases such as chronic hepatitis, ulcerative colitis and chronic skin ulcers and these diseases predispose the patients to cancer development, our results suggest a novel pathway through which TNFa promotes cancer development through induction of gene mutations, in addition to the previously reported mechanisms in which NF-?B activation was implicated. No significant financial relationships to disclose.
Informal decision support networks and treatment decisions for breast cancer.
Authors: Sarah T. Hawley, Nancy K. Janz, Rose Juhasz, Steven J. Katz
Journal: Journal of Clinical Oncology (2013)

24 Background: Although nearly 80% of breast cancer patients have someone with them during surgical consultations, there is little research that examines the extent, nature, or impact of informal decision support persons (DSPs) such as partner/spouse, other family members, or friends on breast cancer treatment decision making. Methods: Two data sources were used: 1) A population based sample of patients recently diagnosed in 2006/7 in the Detroit and Los Angeles SEER catchment areas completed a survey 9 months (N=1837, 72% response rate); and 2) A pilot survey study of a convenience sample of 150 breast cancer patients at three clinical sites surveyed within 18 months that examined more details on the extent and nature of informal decision support networks, including: a) quantity and type of DSPs involved in their treatments, b) number of appointments attended by DSPs, and c) patient-reported satisfaction with DSP’s involvement in treatment decision making. Results: Both a spouse/partner and another family member were very important in treatment decision-making for 33% of patients; a spouse/partner alone was very important for 19%; a family member alone was very important for 13%. A spouse/partner or friends were not important in treatment decision making for 24% of patients. Only 19% of patients reported that a friend was very important in treatment decision making. Friends were much more frequently endorsed among patients with family involvement (45%) vs those without family involvement (5%). Latina patients significantly more often reported that the opinion of a family member was very important vs. other race/ethnic groups (71% vs. 39%, p&lt;0.001). Patients in the pilot study reported an average of 2.67 DSPs were involved in locoregional decision making (SD = 2.57 ) vs. an average of 0.8 (SD=1.03) for involvement in systemic treatment decision making. Conclusions: Many breast cancer patients rely on some informal decision support, but there is a very wide variation in the extent and nature of this support. Further work is needed to understand how to best incorporate DSPs into the treatment decision process. Additional findings will be presented to further describe the impact of informal treatment decision support for women with breast cancer.