tbuckley/cabot-search huggingface dataset:
Metastatic germ cell tumors: modeling for response to chemotherapy.
Authors: D F Bajorin, M Mazumdar, M Meyers, R J Motzer, V Vlamis, P Lin, G J Bosl
Journal: Journal of Clinical Oncology (1998)

PURPOSE This study sought to determine factors that predict response to chemotherapy for patients with advanced germ cell tumors (GCTs), to evaluate different methods by which serum tumor markers can be used to predict response independent of assay method, and to develop criteria to guide allocation to clinical trials. METHODS Pretreatment data from 796 patients treated with platinum-based chemotherapy on Memorial Hospital protocols from 1975 to 1990 were analyzed. Multivariate analyses were performed on a developmental data set (n = 597) to assess for independently significant predictors of response. Predictive models developed using these methods were confirmed on the validation set (n = 199). RESULTS Independently significant factors for response included a mediastinal primary tumor (.015), pure seminomatous histology (.002), metastases to nonpulmonary visceral sites (bone, liver, and brain; .0001), and the pretreatment values of lactate dehydrogenase (LDH; .0001) and human chorionic gonadotropin (HCG; .0001). The likelihood of complete response (CR) was increased by seminomatous histology and decreased by the other factors. Serum levels of HCG and LDH could predict outcome independent of assay methodology. A model to predict good-, intermediate-, and poor-risk categories with CR rates of 92%, 76%, and 39%, respectively, was developed. CONCLUSION The independent prognostic factors of serum tumor markers LDH and HCG, the sites of metastases, and the primary origin of GCTs can predict outcome in patients with advanced GCT. These factors should be considered in the allocation of patients with advanced disease to clinical trials and have been included in the new tumor-node-metastasis (TNM) staging systems developed for the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC).
A phase I/II trial of docetaxel (D) and oxaliplatin (O) in patients with advanced gastric cancer (AGC)
Authors: Y. Park, K. Kim, M. Choi, J. Hong, E. Lee, M. Park, H. Kim, Y. Lee, J. Park, H. Lim, W. Kang
Journal: Journal of Clinical Oncology (2008)

15615 Background: Several different combination chemotherapies for advanced gastric cancer(AGC) have been studied, but there is no great difference in survival benefit compared to previous studies. We designed this phase I/II study of docetaxel(D)-oxaliplatin(O) combination chemotherapy to determine its dose-limiting toxicity, maximum tolerated dose (MTD) and efficacy as a first line treatment in patients with AGC. Methods: Patients aged 18∼70 years, histologically documented gastric adenocarcinoma with measurable disease and adequate organ functions were enrolled.In phase I study, enrolled patients were divided into three groups by doses, and Level I, II, III received D-O 60mg/m2-100mg/m2, 75mg/m2-100mg/m2, 75mg/m2- 130mg/m2 respectively on day 1 every 3 weeks. In phase II study, subjects treated to maximum of 9 cycles of D and O unless there was documented disease progression, unacceptable adverse event or withdrawal of consent. Results: In phase I, there was no dose limiting toxicity (DLT) at all drug levels, so we determined recommended dose of D-O as 75mg/m2-130mg/m2 on level III. In phase II, additional 47 patients were entered into the study. In total, all 50 patients were evaluable. Median follow up duration was 6.5 months (range 0.7–17.3). Overall response rate was 26% (95% CI, 13.8–38.2%) with only 13 partial responders and median duration of response was 3.9 months (range, 0.2–8.8). The time to progression was 2.3 months (range, 1.4–6.6) and 6 months progression free survival rate was 25% (95% CI, 13.0–37.0%). Median overall survival was not reached, and 1 year survival rate was 77.2% (95% CI, 65.6–88.8%). The main toxicities (more than grade 3 or 4) were febrile neutropenia (14%), diarrhea (10%), neutropenia (8%) and neurotoxicity (8%). Neutropenia occurred in first 4 cycles, especially 1st cycle. On the other hand, neurotoxicity occurred after 6th cycles. Treatment related mortality occurred in one patient due to peritonitis-related sepsis (2%). Conclusions: It should be further investigated to know whether D and O combination chemotherapy might be another feasible option as a first line treatment in patients with AGC. No significant financial relationships to disclose.
White coat hypertension
Authors: Rémy C Martin-Du-Pan
Journal: JAMA (1988)

<h3>To the Editor.</h3> —Often, when I take the blood pressure reading of a male patient, the reading is higher early in the appointment and returns to normal later during the same office visit. The women patients in the study by Pickering et al<sup>1</sup>may well be relating to "the stereotype of the physician as a male authority figure," but one might find that men also relate to the female physician as an authority figure by displaying a similar blood pressure elevation. Unless the study is repeated using technicians and physicians of both sexes, the only valid conclusions can be that, while "white coat" hypertension is more pronounced when the blood pressure is measured by a physician than by a technician and while women may have higher blood pressure readings when taken by a male physician than by a female technician, the phenomenon may not be more common in women
Efficacy of neoadjuvant doxorubicin and ifosfamide (AI) in myxoid/round cell liposarcoma (MRCL): The M. D. Anderson Cancer Center experience (MDACC).
Authors: D. Katz, P. Boonsirikamchai, R. S. Benjamin, S. Patel, J. A. Ludwig, J. C. Trent, L. Xiao, V. Ravi, H. Choi, D. M. Araujo
Journal: Journal of Clinical Oncology (2010)

10080 Background: Myxoid/round cell liposarcomas (MRCLs) represent a subgroup of soft tissue sarcomas (STSs) with a multinodular gelatinous macroscopic appearance and a unique chimeric FUS-CHOP gene expression. Doxorubicin and ifosfamide (AI), in combination, is an often-used first-line regimen for MRCLs. However, this standard combination is administrated at a wide dosing range with variable efficacy. With the emerging benefit from trabectidin, (ET-743, Yondelis), a marine-derived alkaloid, in MRCLs, we present the response to neoadjuvant AI, as administrated in MRCL patients (pts) at our institute as a historical benchmark. Methods: We reviewed the clinical records and imaging, focusing on treatment and outcome of all pts with MRCL at our institute from Jan. 2000 to Dec 2009. Pts were treated for 4 - 6 cycles with neoadjuvant doxorubicin (75-90 mg/m2 continuous infusion over 72h q3wk), and ifosfamide (2.5 g/m2 daily × 4 q3wk) with mesna. Main endpoints were: objective response rate by RECIST and Choi criteria (defining response as a decrease in tumor size of ≥10%), time to maximal response and disease free survival (DFS). Results: Clinical data and imaging were available for 24 pts. Median age was 42y (14-72), female:male ratio was 1:1.4, median tumor largest diameter prior to AI was 14.9 cm (6-23.3). Twenty-two tumors were located in the lower extremity, one in the neck and one in the perineum. Partial response rate was 41.6% (n=10) by RECIST and 83.3% (n=20) according to Choi criteria. Tumor diameter decreased by an average of 26.5% (6.2-56.1) and average time to maximum response was 4.2 months. No disease progression or fatalities occurred. Radiotherapy was used in 19/24 pts and all pts underwent surgery with an R0 intent; however, 5 were found to have positive margins. During a median follow up of 54.1 months (95% CI 34 to 78.1) 6 pts developed distant recurrences (2 with positive margins) diagnosed at a median of 23 months (14-50) following surgery of whom two died. The estimated lower limit of 95% CI for median DFS time was 50 months with a 5 year DFS rate of 0.68 (95% CI 0.49 to 0.95). Conclusions: These results confirm the high activity of neoadjuvant AI in MRCL pts. No significant financial relationships to disclose.
Risk of therapy related myelodysplasia and acute myeloid leukemia (t-MDS/AML) in children exposed to alkylating agents, anthracyclines, platinum compounds and epipodophyllotoxins: a report from Children’s Oncology Group (COG)
Authors: S. M. Shankar, L. Chen, T. Zhou, M. D. Krailo, G. Reaman, S. Bhatia
Journal: Journal of Clinical Oncology (2008)

10005 Background: Alkylating agents damage cellular DNA by producing DNA cross links, while epipodophyllotoxins inhibit topoisomerase II, and both are known to be potentially leukemogenic. Platinum compounds and anthracyclines exert their cytotoxic effects through similar mechanisms. The leukemogenic potential of platinum compounds and anthracyclines is less clear, and was explored in this study. Methods: A nested case-control study design was used. The cases were children diagnosed with t-MDS/AML between 1979 and 2000. For each case, multiple controls (1–4) were randomly selected from children treated on COG therapeutic protocols. Controls were matched with the cases for primary diagnosis, date of diagnosis and duration of follow-up. Cumulative exposures to alkylating agents, anthracyclines, platinum compounds, and epipodophyllotoxins were summarized. Conditional logistic regression was used for estimation of odds ratios. Results: A total of 71 cases and 219 controls were included in this study. Univariate analysis revealed associations between exposure to all four groups of agents at varying dose levels (above or below median dose): alkylating agents (< 8 gm/m2: OR=0.7, p=0.5; ≥8 gm/m2: OR=2.5, p=0.04); anthracyclines (<360 mg/m2:OR=3.1, p=0.2; ≥360 mg/m2: OR=4.2, p=0.09); platinum compounds: (<480mg/m2: OR=3.6, p=0.04; ≥480 mg/m2: OR=3.3, p=0.03); and epipodophyllotoxins (<3 gm/m2: OR=5.0, p=0.002, ≥ 3 gm/m2: OR=1.05, p=0.9). However, multivariate analysis, adjusted for exposures to all four agents (presence or absence of exposure), revealed therapy with platinum compounds (OR=5.9; p=0.004) and epipodophyllotoxins (OR=3.6; p=0.007) to be the only independent risk factors for development of t-MDS/AML. No clear dose response relationship could be established. Conclusions: Children treated with platinum compounds and epipodophyllotoxins for their primary cancer have a 3–6 fold higher risk of developing t-MDS/AML, after adjusting for known exposure to alkylating agents and anthracyclines. Further studies need to focus on the mechanism of t-MDS/AML associated with these exposures. No significant financial relationships to disclose.
High affinity Fc receptor binding and potent induction of antibody-dependent cellular cytotoxicity (ADCC) <i>in vitro</i> by anti-epidermal growth factor receptor antibody cetuximab
Authors: X. Kang, D. Patel, S. Ng, M. Melchior, D. Ludwig, D. Hicklin J
Journal: Journal of Clinical Oncology (2007)

3041 Background: Cetuximab is an IgG1 monoclonal antibody specific for human epidermal growth factor receptor (EGFR). Cetuximab acts as a functional antagonist by blocking ligand (EGF and TGFa) binding to EGFR and, therefore, inhibits EGFR activation and downstream signaling in tumor cells. Methods: In the present study, we analyzed the binding activity of cetuximab to human Fc receptors and tested whether cetuximab can elicit antibody-dependent cellular cytotoxicity (ADCC) in vitro using tumor cell lines expressing various levels of EGFR. Results: Cetuximab bound to human FcRI and FcRIII with high affinity (EC 50 of 0.13 nM and 6 nM, respectively), whereas an aglycosylated form of cetuximab or an IgG2 antibody to EGFR (panitumumab) did not bind to FcRI and FcRIII. A panel of head and neck, colon, and breast tumor cell lines were tested for cetuximab-mediated ADCC using human peripheral blood mononuclear cells (PBMC) from normal donors as effector cells. We found that cetuximab-induced ADCC to these tumor cell lines ranging from 20–90% specific killing. Interestingly, the extent of ADCC induced by cetuximab correlated with the level of EGFR expression on cell surface. The aglycosylated form of cetuximab or panitumumab, did not elicit ADCC of EGFR expressing tumor cells, even though cetuximab and panitumumab bind to EGFR with similar affinity (Kd=87 pM and 83 pM, respectively). To identify the immune cell population responsible for ADCC, NK cells were isolated from PBMC and tested in an ADCC assay. Purified NK cells elicited high levels of specific killing of cetuximab bound tumor cells, suggesting that NK cells are one of effector cell populations in human PBMCs responsible for the observed ADCC activity. Conclusions: Thus, cetuximab can effectively link effector cells to EGFR expressing tumor cells and mediate potent ADCC against EGFR-expressing human tumors. [Table: see text]
Growth of Cells &lt;italic&gt;In Vivo&lt;/italic&gt; in Diffusion Chambers. I. Survival of Homografts in Immunized Mice&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Glenn H. Algire, James M. Weaver, Richmond T. Prehn
Journal: JNCI Journal of the National Cancer Institute (1954)

Journal Article Growth of Cells In Vivo in Diffusion Chambers. I. Survival of Homografts in Immunized Mice Get access Glenn H. Algire, Glenn H. Algire Laboratory of Biology, National Cancer Institute,3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar James M. Weaver, James M. Weaver Laboratory of Biology, National Cancer Institute,3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Richmond T. Prehn Richmond T. Prehn Laboratory of Biology, National Cancer Institute,3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 3, December 1954, Pages 493–507, https://doi.org/10.1093/jnci/15.3.493 Published: 01 December 1954 Article history Received: 06 August 1954 Published: 01 December 1954
Phase-II-study with bendamustine / carboplatin in untreated patients with extensive disease small cell lung cancer
Authors: W. Koester, G. Stamatis, N. Niederle, A. Heider, K. Avramidis, H. Wilke, M. Stahl
Journal: Journal of Clinical Oncology (2004)

7265 Background: Bendamustine is an alkylating agent with promising antitumor activity in first line treatment of pts. with metastatic small cell lung cancer (ED-SCLC). Two phase-II-studys showed objective response rates (ORR) between 41 and 50 %. A phase-I-study did demonstrate activity and low toxicity of the Bendamustine / Carboplatin combination (PASCO, Vol 21; 2002). Methods: From 4/02 to 9/03, 29 pts. (22 male, 7 female; median age 63 years (range 43 – 75); WHO-PS 0 - II) with ED-SCLC (no brain metastasis) were treated with Carboplatin AUC 5 day 1 and Bendamustine 80 mg/m2 days 1 and 2 q 3 weeks. Results: 119 cycles are evaluable. Severe (grade III / IV) non-hematological side-effects were observed in only 2.5 % of pts. (one grade III obstipation and one infection grade III and IV, respectively). Alopecia was not seen in any pts.. Leukocytopenia and thrombocytopenia WHO grade III (IV) occured in 13 (0,8) % and 4 (1,7) % of all cycles, respectively. Two non-treatment related deaths occured during chemotherapy. The ORR are 75 % (PR) with NC in another 10 % and PD in 15 % of pts.. The median time to progression is actually 22+ weeks with a median overall survival of 36+ weeks. Conclusions: The combination of Bendamustine and Carboplatin is active in patients with ED-SCLC. Especially the low rates of severe side-effects are promising for these pts. with multiple co-morbidities. Therefore, further evaluation of this regimen in a phase-III-trial is warranted. No significant financial relationships to disclose.
Comprehensive Geriatric Assessment (CGA): Reliable tool for tailored oncologic treatment
Authors: M. Mangia, M. Dieli, B. Merelli, E. Arnoldi, G. D. Beretta, R. Labianca
Journal: Journal of Clinical Oncology (2008)

20679 Background: Aging is a process different from person to person, which is influenced by several factors. Comprehensive Geriatric Assessment (CGA) should lead to a more scientific approach to the elderly cancer patient, aimed to the identification and sometimes treatment of oncological and medical problems. Methods: We have ideated GONG model for CGA with the purpose of selecting patients eligible for oncological treatment or supportive care only, and then used it to evaluate 351 patients from April 2004 to 0ctober 2007. Results: Their mean age was 76.4 years old (22.81% were older than 80), male/female ratio was 1.2. Distinguish three categories of patients: frail; border-line (frail patients with a good functional status but Charlson Index > 8, or a bad functional status with a low Charlson score); and not frail. Our evaluation included also nutritional, psychological and cognitive assessment. 39 patients were classified as frail (11.11%), 77 as border-line (21.94%), 235 as not frail (66.9%). In the group of frail patients 28.21% were treated (most of all had small cell lung cancer), whereas the majority in the other groups (89.79% of not frail and 85.71% of border-line patients) received chemotherapy. Overall survival was better in the patients who received chemotherapy: 9.9, 6.8 and 6.7 months in not frail, border-line and frail respectively after treatment, while 8.7, 4.0 and 2.0 months after supportive care (P=0.030). There was an improvement in survival also in frail patients after treatment versus supportive care (P=0.015) and between not frail and border-line after chemotherapy (P=0.030). Conclusions: CGA represents an useful and essential tool for the management of geriatric cancer patients: in fact it can select group of patients with different prognosis for treatment planning and, in the follow-up of treated patients, can guide further therapeutic decisions. Besides its easy reproducibility could make it a potential instrument in randomized clinical trials aimed to the evaluation of the impact of oncological treatments on disease and quality of life. Furthermore, the possibility to plan ‘tailored‘ treatments, of oncological or supportive type, can obviously have favorable social and economic effects. No significant financial relationships to disclose.
Phase II trial of fenretinide (4-HPR) in recurrent ovarian and primary peritoneal carcinoma: A California Cancer Consortium trial
Authors: A. A. Garcia, R. Morgan, M. McNamara, S. Scudder, D. Tsao-Wei, S. Groshen, T. Frgala, Y. Kim, C. P. Reynolds
Journal: Journal of Clinical Oncology (2004)

5056 Background: 4-HPR is a synthetic retinoid that, in contrast to other retinoids is cytotoxic rather than a differentiation inducer. Induction of tumor cell ceramide and reactive oxygen species have both been implicated in 4-HPR cytotoxicity. 4-HPR inhibited the growth of ovarian cancer cell lines in vitro with 1–10 μmolar concentrations in a dose dependent manner. A recent phase I study achieved higher levels using an intermittent dosing schedule. Methods: We designed a phase II study to evaluate the activity, toxicity profile and pharmacokinetics of 4-HPR in recurrent ovarian cancer. 4-HPR was administered at a dose of 900 mg/m2 po bid for 7 days every 21 days. Patients were required to have bi-dimensionally measurable disease and could have received ≤ 3 prior chemotherapy regimens for recurrent disease. Results: 24 patients have been enrolled; 22 are evaluable for response. Median number of prior chemotherapy regimens is 3 (range: 1–3). Only 5 patients developed grade 3 or 4 toxicity: 1 grade 3 anemia, 1 grade 4 fatigue, 1 grade 3 diarrhea, 1 grade 3 nausea, and 1 with grade 3 vomiting, diarrhea and abdominal pain. There were no treatment related deaths. The median number of cycles was 2 (range 1–35). The median number of 4-HPR cycles was 2 (range 1–35). Pharmacokinetics obtained in 18 patients showed a day 7 mean Cmax of 7.8 ± 4.7 μM (range 0.61 to 14.6 μM). There have been no objective responses; 8 patients (33%) achieved stable disease. The median progression-free survival (PFS) was 1.5 months (95% CI 1.2–4.1) and the median survival was 9.2 months (CI 4.7–13.4). Six patients remained free of progression for more than 6 months (range 6–25); PFS at 6 months is 30% +/- 10%. Conclusions: The encouraging PFS at 6 months suggest 4-HPR may provide clinical benefit to a significant number of patients. 4-HPR was well tolerated and achieved expected plasma levels for the currently employed formulation. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Epimmune Corp.; Pfizer Ortho Biotech
Effect of Postconditioning on Infarct Size in Patients With ST-elevation Myocardial Infarction
Authors: Peder Sorensson, Nawzad Saleh, Frederic Bouvier, Felix Bohm, Magnus Settergren, Kenneth Caidahl, Per Tornvall, Håkan Arheden, Lars Ryden, John Pernow
Journal: Circulation (2009)

Background  Small studies suggest that postconditioning reperfusion interrupted by brief repetitive cycles of reocclusions, may protect the myocardium in the clinical setting.  Objective  To test the hypothesis that postconditioning limits infarct size in relation to the area at risk in patients with ST elevation myocardial infarction (STEMI).  Methods  76 patients (aged 37–87 years) eligible for primary percutaneous coronary intervention due to STEMI were randomised to standard percutaneous coronary intervention (n=38) or postconditioning, consisting of four cycles of 60 s reperfusion and 60 s of reocclusion before permanent reperfusion (n=38).  Results  The area at risk was determined from angiographic abnormally contracting segments. Infarct size was quantified from delayed enhancement MRI on days 6–9. Infarct size, expressed in relation to the area at risk, did not differ between the control group (44%; 30, 56) (median and quartiles) and the post-conditioned group (47%; 23, 63). The slope of the regression lines relating infarct size to the area at risk differed between the two groups. Infarct size was significantly (p=0.001) reduced by postconditioning in patients with large areas at risk. The area under the curve and peak troponin T release and CKMB during 48 h did not differ between patients in the control and postconditioning groups.  Conclusions  This prospective, randomised trial suggests that postconditioning does not reduce infarct size in patients with STEMI in the overall study group. The data indicate that postconditioning may be of value in patients with large areas at risk.  Clinical trial registration information  Karolinska Clinical Trial Registration (http://www.kctr.se). Unique identifier: CT20080014.