tbuckley/cabot-search huggingface dataset:
The triplet combination of irinotecan, oxaliplatin and 5FU/LV (FOLFOXIRI) vs the doublet of irinotecan and 5FU/LV (FOLFIRI) as first-line treatment of metastatic colorectal cancer (MCRC): Results of a randomized phase III trial by the Gruppo Oncologico Nord Ovest (G.O.N.O.)
Authors: A. Falcone, G. Masi, I. Brunetti, G. Benedetti, O. Bertetto, V. Picone, S. Chiara, M. Merlano, S. Vitello, S. Ricci
Journal: Journal of Clinical Oncology (2006)

3513 Background: We demonstrated interesting activity and manageable toxicities for the FOLFOXIRI regimen in phase I-II studies. Methods: The G.O.N.O. conduced a phase III study comparing FOLFIRI (CPT11 180 mg/sqm d1, l-LV 100 mg/sqm d1+d2, 5FU 400 mg/sqm bolus d1+d2, 5FU 600 mg/sqm 22-h inf. on d1+d2, arm A), to FOLFOXIRI (CPT11 165 mg/sqm d1, LOHP 85 mg/sqm d1, l-LV 200 mg/sqm d1, 5FU 3200 mg/sqm 48-h inf. starting on d1, arm B). Both treatments were repeated every 2 weeks and at progression to FOLFIRI a FOLFOX combination was recommended. Selection criteria included measurable and not resectable MCRC, age 18–75 years, no prior chemotherapy for advanced disease. Primary endpoint was response rate (RR) and planned accrual was 240 pts. Secondary endpoints were PFS, OS, post-CT R0 surgical resections, safety and QoL. Results: A total of 244 pts were randomized. Main toxicities were (arm A/arm B): grade 3–4 diarrhea 12%/20%, grade 3–4 vomiting 2%/7%, grade 3–4 stomatitis 3%/5%, grade 2–3 peripheral neurotoxicity 0%/20%, grade 4 neutropenia 11%/17%, febrile neutropenia 3%/5%. Two pts in each arm died within 60 days, but no toxic deaths occurred. Responses, assessed by investigators, were (arm A/arm B): complete 6%/8%, partial 35%/58%, stable 33%/21%, progression 24%/11%, for an overall RR of 41% vs 66%, p=0.0002. RR confirmed by an external panel was 34%/60%, p&lt;0.0001. This increased activity allowed a radical secondary resection of mts in a greater percentage of patients in the FOLFOXIRI arm (6% vs 14%, p=0.05, among all 244 pts and 12% vs 36%, p=0.02, among 81 patients with liver mts only). At a median follow-up of 15.2 months 112 vs 104 pts have progressed and 81 vs 65 have died with a significant improvement in progression-free and overall survival in favor of the triplet (median PFS 6.9 vs 9.8 mos, HR: 0.63, p=0.0006; median S 16.7 vs 22.6, HR:0.70, p=0.032). Conclusions: The FOLFOXIRI regimen is feasible with manageable toxicities and significantly increases RR, R0 resection of mts, PFS and overall S compared to FOLFIRI. (Partially supported by Fondazione ARCO). [Table: see text]
Updated results of an exploratory gene expression analysis for primary esophageal cancer (PEC) patients (pts) treated with oxaliplatin (OXP), protracted infusion (PI) 5FU and radiation (XRT)
Authors: L. P. Leichman, D. Lawrence, K. Clark, H. Nava, E. Nava, C. G. Leichman, G. Proulx, J. Berdzik, W. Greco, L. Pendyala
Journal: Journal of Clinical Oncology (2004)

4014 Background: In a study designed to explore the relationship between expression of TS, γGCS, γGT, ERCC-1 and XPA genes and clinical outcome for 38 pts with PEC, who received OXP (85 mg/m2 day (D)1, D15 and D29), PI 5FU (180 mg/m2 D8-D42 ) and XRT (5040 cGy beginning D8 for 28 fractions) TS appeared to be prognostic for survival (Leichman et al., Proc. ASCO, 22:263, 2003). Because recurrence and deaths have continued, an updated analysis for pts followed through October 2003 is presented including expression of DPD and MRP-2 genes. Methods: Pts had endoscopic biopsies of PEC prior to OXP (D1), prior to 5FU and XRT (D8) and at the end of treatment (ET). Gene expression was assayed typically in 2 specimens at each time point in 29 (ET) to 37 (D1) pts by real time QRT-PCR and expressed relative to β-actin. The mean mRNA levels at each time were logarithmically transformed and using Cox proportional hazards model with time-dependent covariates explored for relationships to survival (S) and progression free survival (PFS). Results: Overall median S (n=38) and PFS (n=38) are 26.9 and 12.1 months (mo) respectively at a median follow-up of 31 and 30 mo for the censored pts. Stage 4 (n=22) versus Stages 2/3 (n=16) showed no differences in S (90% C.I. on hazard ratio: 0.9, 3.8) or PFS (90% C.I. on hazard ratio: 0.9, 3.2). Now, a year after our initial analysis, only D1 mean XPA expression showed relation to S in a model that included stage (XPA 90% C.I. on hazard ratio: 1.3, 6.9). XPA as a time-dependent covariate at D1, D8 and ET for 28 pts with stage included also showed a relation to S (90% C.I. on hazard ratio: 1.0, 7.5). None of the biomarkers on D1 or as time-dependent covariates showed a relation to PFS. Conclusions: In successive exploratory analyses of PEC pts treated with OXP, 5FU and XRT, TS and XPA, gene expressions demonstrated variable time dependent relationships to survival. Expression of these genes, and their association with survival for PEC pts undergoing multimodality are appropriate for further larger studies. (Supported by CA 915490 and CA 16056) Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Synthalabo
Effect of prophylactic administration of recombinant human thrombopoietin on chemotherapy-induced severe thrombocytopenia in patients with advanced non-small cell lung cancer: A prospective self-control clinic study.
Authors: S. Lu, Y. Xu
Journal: Journal of Clinical Oncology (2010)

2569 Background: To evaluate the clinic efficacy of prophylactic administering of recombinant human thrombopoietin (rhTPO) attenuating chemotherapy-induced severe thrombocytopenia in patients with advanced non-small cell lung cancer. Methods: 24patients with advanced non-small cell lung cancer had chemotherapy-induced severe thrombocytopenia in control cycle. In prophylactic treated cycle, all patients received prophylactic administering of recombinant human thrombopoietin (rhTPO, TPIAO, 3SBio Inc, China). In prophylactic treated cycle, rhTPO of the dosage of 300U kg-1 d-1 was prophylactic administered subcutaneously at D2, D4, D6, D9 for four doses after chemotherapy day (D1). We observed platelet count development, thrombocytopenia, duration of thrombocytopenia, and the adverse events of rhTPO prophylactic administered after chemotherapy. Results: In prophylactic treated cycle, it was noticed that the platelet nadir after chemotherapy in prophylactic treated cycle was higher than its in control cycle (mean nadir ± SEM, 56 ± 16 × 109/L vs. 28 ± 13 × 109/L, p < 0.001), and the duration of thrombocytopenia after chemotherapy in prophylactic treated cycle was shorter than its in control cycle (mean duration ± SEM, 8 ± 2 d vs. 12 ± 3 d, p < 0.001). There was no difference between the prophylactic treated cycle and control cycle in the time to platelet nadir (mean time ± SEM, 13 ± 4 d vs. 14 ± 2 d, p > 0.05) and the recovery platelet peak after chemotherapy (median, 182 × 109/L vs. 187 × 109/L, p > 0.05). We also noticed that the area under curve (AUC) of platelet count development (21 days) in prophylactic treated cycle was bigger than its in control cycle (mean AUC ± SEM, 3517 ± 685 × 109/L vs. 2063 ± 436 × 109/L, p < 0.001). Conclusions: Recombinant human thrombopoietin (rhTPO) prophylactic administered after chemotherapy attenuates chemotherapy-induced severe thrombocytopenia and shortens the duration of thrombocytopenia in patients with advanced non-small cell lung cancer who have a history of chemotherapy-induced severe thrombocytopenia. No significant financial relationships to disclose. No significant financial relationships to disclose. No significant financial relationships to disclose.
Managing asthma in the outpatient clinic: Is the diagnosis of asthma confirmed objectively according to guidelines?
Authors: Lise Stensen, Celeste Porsbjerg, Asger Sverrild, Birgitte Nybo Jensen, Backer Vibeke
Journal: European Respiratory Journal (2012)

BACKGROUND: GINA guidelines recommend that a diagnosis of asthma is confirmed by an objective measurement of lung function or the presence of airway hyperresponsiveness. However, currently no diagnostic flowchart exists on asthma, and objective tests are used inconsistently.

AIM: To examine the use of diagnostic tests in newly referred patients with possible asthma in a specialized outpatient clinic.

METHODS: The MAPOut I study is a retrospective observational study of all patients consecutively referred to a tertiary hospital specialist clinic over a 12-month period, on suspicion of asthma (n=221).

Data on lung function, peak flow, reversibility to beta2-agonist and airway hyperresponsiveness (AHR) was collected.

RESULTS: Of 221 patients referred to the outpatient clinic with possible asthma, 128 (58.4%) were diagnosed with asthma. At least one objective test was performed in 103 (80.5) of the 128 subjects diagnosed with asthma (reversibility (57.8%), bronchial provocation (53.1%), PEF monitoring (5.0%).

Among these 128 subjects, 80 had at least one positive test confirming presence of disease, corresponding to 63% of all subjects diagnosed with asthma.

CONCLUSION: Among patients diagnosed with asthma in a tertiary specialist clinic, the diagnosis of asthma was confirmed objectively in 63%. In a significant proportion of patients, treatment decisions were based solely on the presence of symptoms.
Evidence of genetic transmission in African iron overload.
Authors: Victor M. Moyo, Eberhard Mandishona, Sandra J. Hasstedt, Innocent T. Gangaidzo, Zvenyika A.R. Gomo, Hlosukwazi Khumalo, Thokozile Saungweme, Clement F. Kiire, Alan C. Paterson, Peter Bloom, A. Patrick MacPhail, Tracey Rouault, Victor R. Gordeuk
Journal: Blood (1998)
Abstract A1-21: NOTCH 1 and NOTCH 3 expressions for early stage of non-small cell lung cancer
Authors: Eun Kyung Cho, Seung Yeon Ha, Jae Ik Lee, Junsick Hong, Sun Jin Sim, Jinny Park, Dong Bok Shin, Jae Hoon Lee
Journal: Cancer Research (2015)

Abstract Backgrounds: Notch gene Encode 300kDa single-pass transmembrane receptors. It can variously serve as an oncogene or a tumor suppressor and a repressor or inducer of terminal differentiation. It also regulate cell division, differentiation and survival of stem and/or progenital cells in wide range tissues. We examined Notch 1 and 3 to study the correlation of Notch expression and prognosis for non-small cell lung cancer. Methods: Paraffin-embedded tissue microarrays were constructed. We analyzed Notch 1 and 3 by immunohistochemical stain on surgical tumor specimens. Results: One hundred fifty-nine of 185 resected tissues for lung cancer (median age 62 years) were available for immunohistochemical stain. The types of tumor histology were adenocarcinoma;54, squamous cell carcinoma:79, others;26. 121 patients were taken lobectomy and 38 were done pneumonectomy. Notch 1 and 3 receptors were detected in 119 (74.8%) and 130 (81.7%) of total 159 (M:F=114:45) tumor tissues, respectively. Notch 1 receptors showed higher expressions on squamous cell carcinoma than non-squamous cell carcinoma (58.8% vs. 37.8%, p=0.03). However, it was not correlated with sex, smoking status or advanced stages. Five year-relapse free survival (RFS) and overall survival (OS) were 57.4 % and 59.3 % in 159 patients, respectively. Patients with any expression of Notch1 or 3 have correlated with neither RFS nor OS. 5 year OS for patients who showed Notch 3 expression were 62 % and the others were 47.8%, however, it was not statistically significant (p= 0.165). Both of their expressions were detected in 106 of 159 (66.7%) tumor tissues. Sixteen (10 %) had negative expressions in both of them. The patients with both positive expressions had the tendency of longer OS than all negative patients. Their 5 year OS were 60.8 % vs. 38.2% (p=0.068) and 5 year RFS were 56.5% vs. 49.7 % (p=0.35). Conclusions: Notch 1 showed higher expression on squamous cell carcinoma. Neither Notch 1 nor 3 have correlated with RFS or OS, but patients with both expressions had the tendency of longer overall survival. Citation Format: Eun Kyung Cho, Seung Yeon Ha, Jae Ik Lee, Junsick Hong, Sun Jin Sim, Jinny Park, Dong Bok Shin, Jae Hoon Lee. NOTCH 1 and NOTCH 3 expressions for early stage of non-small cell lung cancer. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-21.
The impact of lymph node dissection in patients with colorectal cancer
Authors: R. W. Gentry, R. Govindarajan, H. J. Spencer, G. Dykstra-Long
Journal: Journal of Clinical Oncology (2007)

17055 Background: The role of extended lymphadenectomy on survival of patients with colorectal cancer is unclear. Survival in these patients is inversely proportional to the stage of disease. The prognostic significance of inadequate lymph node dissection is not understood. To understand the impact of the number of lymph nodes removed at the time of surgery on survival, we conducted a retrospective study of patients with colorectal cancer treated at the Central Arkansas Veterans Healthcare System, Little Rock, AR. Methods: Data on 531 patients with a diagnosis of colorectal cancer from January 1991 to October 2005 was obtained from the tumor registry. The number of lymph nodes dissected the number of positive and negative lymph nodes for each patient, treatment received and overall survival was analyzed. The number of resected nodes was grouped as follows: none (LNG0), 1–5 (LNG1), 6–10 (LNG2), and &gt; 10 (LNG3). Log rank test was used to evaluate difference in survival between the groups. Results: There were 451 Caucasians, 80 African Americans, 523 males and 8 females in the study. The median age was 69 yrs (range: 29–100). Rectal cancer patients had fewer nodes dissected compared to colon cancer (p &lt;0.001). There was no survival difference between LNG0, LNG1, LNG2 and LNG3 (p=0.435). The number of lymph nodes removed did not have an impact on survival among those who had node negative disease (0.435) and node positive (0.458) disease. LNG0 patients had the same prognosis as those with node negative disease (P=0.435) who had better survival compared to node positive disease. (p=0.029). However, LNG0 patients had similar survival compared to LNG1 subset of patients and those in LNG3 had a trend towards better survival, though not statistically significant. LNG0 subjects received less chemotherapy (p=0.018) and radiation therapy (p=0.01) compared to those who had lymphadenectomy. Conclusions: The number of nodes removed at the time of surgery did not affect survival in subjects with node negative and node positive disease. Patients who did not have any identifiable nodes at the time of surgery had the same prognosis as those who had node negative disease. Patients with more than 10 negative nodes dissected had a trend towards better survival although not statistically significant. No significant financial relationships to disclose.
Evaluation of hormone receptor and benefit from adjuvant chemotherapy in breast cancer patients with intermediate- and high-risk disease.
Authors: C. Kurzeder, A. Woeckel, T. Kuehn, E. Schlicht, M. Blettner, R. E. Felberbaum, M. Wischnewsky, R. Kreienberg
Journal: Journal of Clinical Oncology (2010)

6130 Background: The BRENDA Study network aims to improve quality of care for breast cancer patients by analyses of treatment related outcome within a network of specialized breast cancer centers in Germany. The population studied differs markedly from those populations found to be included in prospective trials. Despite a multitude of positive chemotherapy trials the role of adjuvant chemotherapy in subpopulations of breast cancer patients is still controversial. We investigated to which extent subpopulations of breast cancer patients defined by quantitative strong expression of hormone receptors benefit from adjuvant chemotherapy. Methods: Estrogen receptor (ER) and progesterone receptor (PR) content of 3,971 patients who received primary therapy for early breast cancer was recorded and quantified by standardized immunohistochemical evaluation. The Nottingham prognostic index (NPI) served to classify the patients' prognostic baseline risk. Results: Strong expression of ER and PR was found in 45% and 30.6%, respectively. In patients with strong expression of ER and/or PgR no significant difference with respect to recurrence free survival (RFS) and overall survival (OS) was found in patients receiving endocrine therapy alone or in combination with chemotherapy. Calculated hazard ratios for RFS were 0.98 for patients with intermediate risk (95% CI: 0.48-2.01; p = 0.949) and 1.03 for high-risk patients (CI: 0.46-2.31; p = 0.948). Risk of recurrence was significantly increased in patients receiving chemotherapy only when compared with patients receiving additional or alternative hormonal therapy in the high-risk group of patients (HR = 2.45; CI: 1.04-5.80; p = 0.042). Conclusions: The incremental benefit of chemotherapy when added to a hormonal therapy regimen in patients with quantitative strong hormone receptor expression has to be questioned. Algorithms based on patients risk alone might cause overtreatment with ineffective chemotherapy in a considerable fraction of patients receiving treatment outside clinical trials. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Novartis, Pfizer
Bortezomib‐based triplets are associated with a high probability of dialysis independence and rapid renal recovery in newly diagnosed myeloma patients with severe renal failure or those requiring dialysis
Authors: Meletios A. Dimopoulos, Maria Roussou, Maria Gavriatopoulou, Erasmia Psimenou, Evangelos Eleutherakis‐Papaiakovou, Magdalini Migkou, Charis Matsouka, Despoina Mparmparousi, Dimitra Gika, Eftychia Kafantari, Dimitrios Ziogas, Despoina Fotiou, Ioannis Panagiotidis, Evangelos Terpos, Efstathios Kastritis
Journal: American Journal of Hematology (2016)

Renal failure (RF) is a common and severe complication of symptomatic myeloma, associated with significant morbidity and mortality. Such patients are commonly excluded from clinical trials. Bortezomib/dexamethasone (VD)‐based regimens are the backbone of the treatment of newly diagnosed MM patients who present with severe RF even those requiring dialysis. We analyzed the outcomes of 83 consecutive bortezomib‐treated patients with severe RF (eGFR &lt; 30 ml/min/1.73 m 2 ), of which 31 (37%) required dialysis. By IMWG renal response criteria, 54 (65%) patients achieved at least MRrenal, including CRrenal in 35% and PRrenal in 12%. Triplet combinations (i.e., VD plus a third agent) versus VD alone were associated with higher rates of renal responses (72 vs. 50%; P = 0.06). Fifteen of the 31 (48%) patients became dialysis independent within a median of 217 days (range 11–724). Triplets were associated with a higher probability of dialysis discontinuation (57 vs. 35%). Serum free light chain (sFLC) level ≥11,550 mg/L was associated with lower rates of major renal response, longer time to major renal response, lower probability, and longer time to dialysis discontinuation. Rapid myeloma response (≥PR within the first month) was also associated with higher rates of renal response. Patients who became dialysis‐independent had longer survival than those remaining on dialysis. In conclusion, VD‐based triplets are associated with a significant probability of renal response and dialysis discontinuation, improving the survival of patients who became dialysis independent. Rapid disease response is important for renal recovery and sFLCs are predictive of the probability and of the time required for renal response. Am. J. Hematol. 91:499–502, 2016. © 2016 Wiley Periodicals, Inc.
Side Effects of Chemotherapy
Authors: Daniel Castellano, Ricardo Hitt, Hernán Cortés-Funes, Alberto Romero, Jose Luis Rodriguez-Peralto
Journal: Journal of Clinical Oncology (2000)

Article Tools Side Effects of Chemotherapy Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.3.695 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10653886 Side Effects of Chemotherapy Daniel CastellanoxDaniel CastellanoSearch for articles by this author , Ricardo HittxRicardo HittSearch for articles by this author , Hernán Cortés-FunesxHernán Cortés-FunesSearch for articles by this author , Alberto RomeroxAlberto RomeroSearch for articles by this author , Jose Luis Rodriguez-PeraltoxJose Luis Rodriguez-PeraltoSearch for articles by this author Show More Hospital Universitario "12 de Octubre," Madrid, Spain https://doi.org/10.1200/JCO.2000.18.3.695 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Children in Third World slums [letter]
Authors: Dobbing J
Journal: BMJ (1988)

Dr William A M Cutting  Professor Gopa Kothari do well to rub our noses once again in the obscenity of the poverty of 3rd World slums (18 June p 1683).  They also do well to send British medical students for a spell to such places.  Students will always remember the experience as they will need to because the problem of world poverty shows little sign of being seriously tackled in their lifetimes let alone in ours.  I also fervently applaud their remark  changing cliches will change nothing:  nor will anything short of an objective assessment of the facts including those about breastfeeding supplementation  manufactured  other breastmilk substitutes.  Unfortunately their leading article is not uninfluenced by such cliches.  99% of these children were breastfed.  They say there was no difference in nutritional state between infants who were exclusively breastfed  those who received supplements which implies  supplementary feeding was inadequate in amount and may have reduced milk production by decreasing the childs sucking [my italics].  Is this also an acknowledgement  those who were exclusively breastfed did very badly?  If so it would be better to say so as  is not the usual claim.  Also Dr Cutting  Professor Kothari must know  in poor  undernourished populations it is now believed to be unlikely  supplementation will reduce lactation as it was 1st shown to do in middle class Edinburgh.  It is scarcely surprising  infants under 6 months who were not breastfed had so much more severe malnutrition:  the wonder is  they survived at all.  But to say  at ages over 6 months the benefit of breastfeeding was less clear is another interesting denial of the usual teaching.  We are told  top up feeds with animal or commercial milks...probably do more harm than good yet we have a plea for earlier larger  less contaminated supplementation.  With what?  Could they be more constructive?  Of course I know how impossible it is to feed babies properly in the squalor  they describe but it is the squalor  the poverty which are the problem not the nature of the supplement.  The common suggestion  breastfeeding is the solution with the frequent implication  the manufacturers are the villains (very few mothers indeed had used their products) is too facile a fraud on our well concerned fellow citizens.  The solution to such poverty is much more difficult but the more difficult it is the earlier we should all start looking for it.  Successful lactation (and nothing else will do) is that which provides for the proper growth of the child without detriment to the health of the mother.  Prolonged exclusive breastfeeding fulfills neither condition  to promote it as many do as an easy panacea is misleading.  (full text)