tbuckley/cabot-search huggingface dataset:
Comparison of high-dose and low-dose radiation with and without chemotherapy for children with Hodgkin's disease: an analysis of the experience at the Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania.
Authors: A Maity, J W Goldwein, B Lange, G J D'Angio
Journal: Journal of Clinical Oncology (1992)

PURPOSE In an effort to minimize complications related to high-dose radiotherapy (RT), children with Hodgkin's disease are often treated with low-dose RT (less than 25 Gy) plus chemotherapy. We performed a retrospective study comparing the results in these children with those from children treated with higher doses of RT (30 to 40 Gy) with or without chemotherapy. PATIENTS AND METHODS From 1970 to 1988, 121 patients younger than 18 years of age with newly diagnosed Hodgkin's disease were treated at the Children's Hospital of Philadelphia (CHOP) and the Hospital of the University of Pennsylvania (HUP). Before 1977, most children underwent laparotomy and received high-dose RT with or without chemotherapy. Since then, high-dose RT alone has been reserved for pathologic stage IA and IIA postpubertal children without large mediastinal masses. In general, most postpubertal children with stage IIB through IVB disease or large mediastinal masses and all prepubertal children have received low-dose RT plus chemotherapy without laparotomy. RESULTS The 10-year actuarial survival for all children was 86%, and the event-free survival (EFS) was 67% (median follow-up, 6.6 years). For 58 children treated with low-dose RT plus chemotherapy, 10-year survival and EFS (median follow-up, 6.8 years) were 88% and 67%, respectively. The corresponding figures for 10-year survival and EFS in 48 children treated with high-dose RT with or without chemotherapy were 88% and 66%, respectively. In children receiving combined modality therapy, the in-field failure rate was 7% for sites given between 17.5 and 22.5 Gy and 2% for sites given more than 32.5 Gy. In children receiving RT alone, the failure rate was 5% for sites given more than 32.5 Gy. CONCLUSION We conclude that low-dose RT plus chemotherapy has yielded results comparable to those with higher doses of RT with or without chemotherapy.
A preclinical survey on the efficacy of NSC-290205 in combination with doxorubicin (ADR) in Lewis lung carcinoma (LLC)
Authors: A. Papageorgiou, E. Stergiou, I. Boukovinas, G. Geromichalos, I. Stergiou
Journal: Journal of Clinical Oncology (2006)

17131 Background: NSC-290205 (A) is a hybrid synthetic antitumor ester, which combines a D-lactam derivative of androsterone and nitrogen mustard. Studies on modified steroidal esters of carboxylic derivatives of N,N-bis(2-chloroethyl)aniline, have shown that they exhibit reduced toxicity and increased antitumor activity and specificity. In this study we investigated the antitumor activity of compound A in combination with ADR (AHOP) in comparison with standard CHOP regimen. Methods: C57Bl mice were used for the antitumor evaluation of AHOP/CHOP. Experiments were initiated by implanting the tumor. LLC cells (purchased by NCI, Bethesda, USA) were implanted intramuscularly into the right hind leg as a suspension of 7 × 10 6 cells in 0.1 ml. The antitumor activity was assessed from the inhibition of tumor growth by volume in cm 3 and the oncostatic parameter T/C % according to the protocol of experimental evaluation of antitumor drugs of the NCI, USA. Treatments were given as a single dose (D) on day 1, intermitted dose (D/2 × 3) on days 1, 5, 9 or consecutive dose (D/4 × 9) on days 1 through 9. Results: Treatment with A or cyclophosphamide produced almost equal borderline activity. Moreover, both CHOP and AHOP regimens showed significant and comparable antitumor effect (p &lt; 0.05 by the Wilkoxon test). AHOP caused the maximum effect inhibiting the tumor growth by 67.7% and T/C values of 270%. CHOP was less effective producing 54.8% tumor inhibition and T/C values of 238%. Conclusions: It is very likely that the D-lactamic steroid (androstan) alkylator for A, containing the -NHCO group, combined with ADR, which intercalates between base-pairs, is the explanation for higher activity of AHOP vs. CHOP. This significant effect of NSC-290205 with the anthracycline adriamycin on LLC adds to NSC-290205 advantage for further clinical development. No significant financial relationships to disclose.
Phase I trial of weekly scheduling and pharmacokinetics of titanocene dichloride in patients with advanced cancer.
Authors: C V Christodoulou, D R Ferry, D W Fyfe, A Young, J Doran, T M Sheehan, A Eliopoulos, K Hale, J Baumgart, G Sass, D J Kerr
Journal: Journal of Clinical Oncology (1998)

PURPOSE To determine the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of a weekly schedule of titanocene dichloride (TD) and to define the pharmacokinetics of titanium in plasma and urine. PATIENTS AND METHODS Twenty patients with a median age of 58 years received 83 courses of TD. TD was given as 1-hour infusion at escalating doses from 70 to 185 mg/m2/wk. Pharmacokinetic analysis was performed in eight patients for total plasma titanium (TPTi) and in three patients for ultrafiltrable titanium (UFTi). RESULTS At the fifth dose level (185 mg/m2/wk), a variety of DLTs were seen in five patients: fatigue in three, bilirubinemia in one, and hypokalemia in two. A further six patients were treated at 140 mg/m2; only one had dose-limiting creatinine elevation and this dose was therefore defined as the MTD. No myelosuppression or alopecia were observed. One patient with adenocarcinoma of unknown primary had a minor response. Pharmacokinetic analysis showed that TPTi maximum concentration (Cmax) values were linear with dose and elimination of TPTi was triphasic with a long terminal half-life (t1/2; median, 165 hours; range, 89 to 592). Between 7% and 24.3% of the total of administered titanium was eliminated in urine over the first 24 hours. In contrast, UFTi elimination was described by a one-compartment model with a t1/2 of 0.41 hours; peak levels of UFTi were 5.2% +/- 2.5% those of TPTi. CONCLUSION The MTD of TD given on a weekly schedule is 140 mg/m2, with cumulative, but reversible creatinine and bilirubin elevation being the DLTs.
Chemoprevention of Breast Cancer: A Model for Change
Authors: V. Craig Jordan, Monica Morrow
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.1.1 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11773145 Chemoprevention of Breast Cancer: A Model for Change V. Craig JordanxV. Craig JordanSearch for articles by this author , Monica MorrowxMonica MorrowSearch for articles by this author Show More Northwestern University Medical School, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL https://doi.org/10.1200/JCO.2002.20.1.1 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Pathological response and its effect on survival with neoadjuvant chemotherapy according to intrinsic subtype in locally advanced breast cancers in north India: Is it different from the West?
Authors: Sushma Agrawal, Punita Lal, Shaleen Kumar, Gaurav Agarwal, Anjali Mishra, Amit Agarwal, Vinita Agarwal, Saroj Kanta Mishra
Journal: Journal of Clinical Oncology (2014)

90 Background: Breast cancer patients commonly present in locally advanced stage (LABC) in our country. We propose to correlate the pathological response to neoadjuvant chemotherapy (NACT) and its impact on survival based on the intrinsic subtypes. Methods: Consecutive patients of LABC who underwent NACT (taxane and or anthracyclines based )followed by definitive surgery and radiotherapy during the period January 2007 to December 2012 were grouped on the basis of intrinsic subtypes (Luminal A, Luminal B, Her-2 Type, Basal). The pathological response to NACT in tumour as well as axillary nodes [complete response (pCR), partial response (pPR)] was correlated with the disease free survival (DFS) and overall survival (OS) at 5 years in the intrinsic subtypes using Kaplan Meier Analysis. Results: Among 208 patients the median age was 46 years (range 24-81 years), 46% premenopausal,54% postmenopausal, presenting tumour and node stage was 15% T2, 40% T3, 45% T4,8% N0, 42% N1, 41% N2, 9% N3.The intrinsic subtypes at presentation were Luminal A (16%), Luminal B (23%), Her-2 Type (23%), Basal (37%).The pCR rate in node was significantly higher in Her-2 type and Basal subtype (Table ). At a median followup of 34 months (range 6-84 mo)the 5 year DFS and OS was significantly higher in patients achieving pCR tumour or node in Her-2 type and Basal subtype (Table ). Conclusions: The pCR rate to NACT in tumour or node seems to be considerably higher in our population than that reported in the western literature. pCR (tumour and node) is a surrogate for both DFS and OS at 5 years in Her-2 and basal subtypes of breast cancer. [Table: see text]
Phase II study of alemtuzumab in lymphoplasmacytic lymphoma: Results of WMCTG trial 02–079
Authors: Z. R. Hunter, M. Boxer, B. Kahl, C. J. Patterson, J. D. Soumerai, S. P. Treon
Journal: Journal of Clinical Oncology (2006)

7523 Background: Alemtuzumab (Campath-1H) is a fully humanized anti-CD52 antibody used to treat B and T-cell disorders. CD52 is widely expressed on bone marrow lymphoplasmacytic cells and growth supporting mast cells in patients with lymphoplasmacytic lymphoma (LPL), including Waldenstrom’s macroglobulinemia (WM). We therefore examined the activity of alemtuzumab in LPL. Methods: 28 patients with LPL, including 27 WM patients were enrolled in this multicenter study. 23 patients were previously treated. Median age was 60 (range 33–75 years), median prior therapies was 2 (range 0–5), and median time from diagnosis was 2.9 (range 0.1–9.0 years). Baseline median bone marrow involvement was 30% (range 5–90%), median serum IgM was 3510 (range 622–12,000 mg/dL) and hematocrit was 35.1 (range 24.4–42.8%). Patients received 3 test doses of alemtuzumab (3, 10, and 30mg IV) followed by 30 mg TIW for up to 12 weeks. All patients received acyclovir and bactrim or equivalent prophylaxis. Results: Twenty-five patients are evaluable for response. 24/25 patients demonstrated a decrease in serum IgM levels (median change -40.5%), for an overall response rate of 76%, which included 8 (32%) partial responders (≤50% decrease in serum IgM), and 11 (44%) minor responders (≥25% decrease in serum IgM). Hematological toxicities were common among previously treated (but not untreated) patients and included G3/4 neutropenia 39%; thrombocytopenia 18%; anemia 7%. G3/4 non-hematological toxicity for all patients included dermatitis 11%; fatigue 7%; and infection 7%. CMV reactivation and infection was commonly seen among previously treated patients and may have been etiological for one death on study. Two other patients also succumbed on study, one related in part to drug therapy for CMV infection and another due to complications of therapy induced thrombocytopenia and Von Willebrand disease. With a median follow-up of 8.5+ months, 11/19 responding patients remain free of progression. Conclusions: Alemtuzumab is highly active in patients with LPL. Hematological and non-hematological toxicities, including CMV reactivation and infection are common among previously treated patients. Further exploration of this agent in LPL, including upfront therapy is warranted. No significant financial relationships to disclose.
Results of the 1972 APA Self-Assessment Program
Authors: HUGH T. CARMICHAEL, BRYCE TEMPLETON, S. MOUCHLY SMALL, PAUL R. KELLEY
Journal: American Journal of Psychiatry (1974)

In 1972 the American Psychiatric Association offered its membership a newly revised Psychiatric Knowledge and Skills Self-Assessment Program. The results reported in this paper were based on the performance of 2,394 participants who indicated that they had used the materials as a "take-home, closed-book" examination. It was found that there was a gradual falloff in psychiatric knowledge with an increasing number of years since the completion of residency training. This trend was more noticeable in the multiple-choice questions than in the patient management section of the program. The authors, while drawing their conclusions with caution, note that the information obtained in this program should disclose "blind spots" in the knowledge of practicing psychiatrists.
Phase I study of PD 0332991, cyclin-D kinase (CDK) 4/6 inhibitor in combination with letrozole for first-line treatment of patients with ER-positive, HER2-negative breast cancer.
Authors: D. J. Slamon, S. A. Hurvitz, S. Applebaum, J. A. Glaspy, M. K. Allison, B. A. DiCarlo, R. D. Courtney, S. T. Kim, S. Randolph, R. S. Finn
Journal: Journal of Clinical Oncology (2010)

3060 Background: PD 0332991 is a potent, oral, small molecule CDK 4/6 inhibitor. In preclinical studies, human luminal ER-positive breast cancer cell lines were uniquely sensitive to G0/G1 arrest and growth inhibition by PD 0332991. In addition, PD 0332991 was synergistic with tamoxifen in vitro. Based on these observations, a phase 1/2 study in combination with letrozole was initiated. Methods: Post-menopausal women with ER-positive, HER2-negative breast cancer were enrolled. Other eligibility criteria included ECOG PS 0 or 1, no brain metastases, and adequate organ function. Phase I assessed the safety and tolerability of the combination. Cycle 1 consisted of PD 0332991 125 mg QD administered for 2 weeks alone followed by 1 week off. In subsequent cycles, PD 0332991 was administered for 3 weeks followed by 1 week off (schedule 3/1) and letrozole 2.5 mg QD. Pharmacokinetic samples were collected to assess the potential for a drug–drug interaction (DDI). Tumor assessments were performed every 8 weeks. Results: 12 pts were enrolled in phase 1; median age was 61 years (range 37–81). Prior systemic treatment included chemotherapy (67%), anastrozole (33%), and tamoxifen (17%). Median duration of treatment is 6 months (range 2–13). 9 pts remain on study, 3 pts discontinued treatment due to disease progression. 3 DLTs were reported: grade 4 neutropenia (n=2) and one patient with dose interruption (<80% PD 0332991 dose administered). Most common adverse events included neutropenia, leucopenia, and fatigue. Best response as assessed by RECIST include 3 pts with partial response (out of 9 pts with measurable disease) and 9 pts with stable disease. Mean plasma exposure AUC0–24 of PD 0332991 in the absence and presence of letrozole (2002 vs. 2043 ng·hr/mL) and letrozole in the absence and presence of PD 0332991 (1,990 vs. 1,730 ng·hr/mL) suggests no DDI. Conclusions: The combination of PD 0332991 and letrozole was generally well tolerated. Based on the DLTs and overall safety profile, the PD 0332991 recommended phase 2 dose is 125 mg QD on schedule 3/1 in combination with letrozole 2.5 mg QD. Encouraging antitumor activity was observed, and a randomized phase 2 study has been initiated. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer
Point-of-care (POC) diagnostic assay for 5-fluorouracil (5-FU) quantitation to enable dose adjustment and detect dihydropyrimidine dehydrogenase (DPD) deficiency.
Authors: J. White, P. Hu, M. Bonen, M. K. Bamat, R. von Borstel
Journal: Journal of Clinical Oncology (2011)

e19562 Background: 5-FU is used in the treatment of 275,000 U.S. cancer patients each year. Patient variability in 5-FU metabolism causes many patients to be under dosed with 5-FU while other patients with slow clearance are overexposed, resulting in 1300 US deaths per year. Monitoring 5-FU levels in individual patients has demonstrated that efficacy and safety can be improved significantly. Wellstat is developing a point-of-care (POC) diagnostic system for monitoring 5-FU levels, giving physicians results in less than 15 minutes. This will enable the rapid detection of 5-FU overexposure due to clearance issues, including DPD deficiency (3-5% of the population) during infusion or following oral administration of capecitabine. Rapid detection of overexposure allows timely intervention with a potential antidote (e.g. uridine triacetate) while real-time detection of suboptimal 5-FU levels allows physicians to safely administer more efficacious doses. Methods: A proprietary monoclonal antibody specific for 5-FU and conjugated with a ruthenium chelate forms the basis of an electrochemiluminescence (ECL) assay. The concentration of 5-FU is inversely correlated to the generation of light. The assay can use whole blood without centrifugation and can deliver POC results in less than 15 minutes. Results: This ECL assay exhibited exquisite sensitivity (lower detection limit < 5 ng/mL) and a dynamic range to 30,000 ng/mL. The calibrator curve range was 9.6 – 30,000 ng/mL 5-FU with coefficients of variation < 7% for quantitation. Minimal cross-reactivity was observed with capecitabine (0.08%), dihydro-5-FU (2.6%) and uracil (0.9%). Chemotherapies commonly co-administered with 5-FU did not interfere. Conclusions: The assay is capable of accurately monitoring 5-FU in plasma, providing results over a wide dynamic range. The POC analyzer system will permit monitoring of 5-FU during infusion and after oral 5-FU prodrugs, enabling identification of patients overexposed to 5-FU due to DPD deficiency or other clearance problems and allowing for individualized 5-FU treatment with improved efficacy and diminished side effects.
Randomized, phase II study of two doses of pemetrexed as first-line chemotherapy for locally advanced or metastatic breast cancer (MBC): Clinical results and exploratory pharmacogenomic analysis
Authors: A. Llombart-Cussac, M. Martin, N. Harbeck, R. Anghel, A. Eniu, A. Melemed, R. Clark, L. Simms, C. Kaiser, D. Ma
Journal: Journal of Clinical Oncology (2006)

3077 Background: Pemetrexed, a folate antimetabolite, has shown varied response in MBC, depending on the dose, vitamin supplementation, and patient pre-treatment status. We conducted a randomized, double-blind, phase II study, in patients with locally advanced or MBC to evaluate 2 doses of pemetrexed. Primary objective was to assess the response rates on the 2 arms. Methods: Women with histologic/cytologic diagnosis of breast cancer, evidence of locally recurrent disease or distant metastasis, not amenable to local therapy were eligible. Patients received pemetrexed (600 mg/m 2 Arm A; or 900 mg/m 2 Arm B), on D1 of a 21-day cycle. All patients received folic acid and vitamin B 12 supplementation. Forty-three patients were planned on each arm. Results: Ninety-two patients (median age 57 years, range 33–81) enrolled: 47 on arm A and 45 on arm B. Arms A and B had response rates of 17.0% (95% CI, 7.7%-30.8%), and 15.6% (95% CI, 6.5%-29.5%), median progression free survival times of 4.2 and 4.1 months, and median times to tumor progression (TtTP) of 4.2 and 4.6 months, respectively. On both arms, a median of 6 cycles was delivered. Toxicity was mild (grade 3/4 toxicity on both arms; neutropenia &lt;20%, leucopenia &lt;9%). Primary tumor samples from 49 patients were assessed for 10 folate or pyrimidine metabolism related gene expressions by reverse transcriptase-polymerase chain reaction methodology. Two markers, folypolyglutamate synthase (FPGS) and thymidine phosphorylase (TP), showed significant results. Best response rates and median TtTP for high vs low FPGS expression subgroups were 37.5% vs 10.0% and 8.6 vs 3.0 months. The corresponding results for TP were 27.6% vs 6.3% and 5.4 vs 1.9 months. Conclusions: Efficacy and safety of the two pemetrexed doses were similar; thus, the lower dose (600 mg/m 2 ) is suitable in patients with MBC. Exploratory biomarker analysis suggests efficacy correlation for FPGS and TP. Further evaluation of these markers appears warranted. [Table: see text]
SAT0098 Validity of Ankylosing Spondylitis and Spondyloarthritis Diagnoses in the Swedish National Patient Register
Authors: U. Lindström, S. Exarchou, V. Sigurdardottir, B. Sundström, J. Askling, J.K. Eriksson, H. Forsblad d'Elia, C. Turesson, L.E. Kristensen, L. Jacobsson
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Epidemiological studies of spondyloarthritis (SpA) are scarce. Using ICD-codes from the Swedish National Patient Register (NPR) offers unique possibilities for such studies. For this purpose, the validity of these ICD-codes needs to be determined. <h3>Objectives</h3> To validate the ICD-codes for ankylosing spondylitis (AS) and SpA in the NPR against established classification criteria (modified New York (mNY), ASAS, Amor and ESSG criteria). <h3>Methods</h3> All patients with an ICD-code of AS or SpA in the NPR 1966-2009 at a visit to a specialist in rheumatology or internal medicine, or corresponding hospitalization, were identified (n=20074). Following a structured procedure to achieve geographical representativeness, 500 random patients with a registered diagnosis of AS or SpA in 2007-2009 were selected. A structured review of clinical records, with extraction of necessary information for the established classification criteria was performed and positive predictive values (PPV) were calculated. <h3>Results</h3> In this cohort 11472 (34% women) patients had received an AS diagnosis and 11004 (56% women) a SpA diagnosis. The overlap group having received both types of diagnoses had similar frequencies for fulfillment of mNY criteria, symptoms and signs of back disease as the group having been coded as AS only. Of those being coded as AS only, the PPV for fulfilling the mNY, any criteria set and any of the included criteria elements were 70%, 89% and 96% respectively. Of those with SpA (without AS ever) the corresponding PPV values were 20%, 79% and 99% respectively. <h3>Conclusions</h3> A diagnosis of AS or SpA (without AS) had a high validity, suggesting that case identification based on ICD-codes in the Swedish NPR can be used for epidemiological studies of these diseases. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2817