tbuckley/cabot-search huggingface dataset:
Association between researcher gender and sex of participants in clinical cancer research
Authors: R. Jagsi, S. Amarnath, A. Motomura, A. Jankovic, N. Sheets, P. Ubel
Journal: Journal of Clinical Oncology (2008)

6607 Background: The National Institutes of Health prioritize adequate representation of women in medical research. Methods: We collected data on researchers & participants from clinical oncology studies published in 2006 in 8 journals (NEJM, JAMA, Lancet, JCO, JNCI, Lancet Oncol, CCR, Cancer). Author gender was determined by inspection of first name or, when necessary, internet searching. Differences in sex distribution of participants by funding source & author gender were assessed using t tests and multivariate linear regression. Results: We identified 2,701 original oncology articles; of these, we analyzed the 661 that were prospective clinical studies, representing 1,097,413 participants (median participants per study = 83). Gender of first author was identified in 95.5% of the studies & was female in 30.4% of these. Gender of senior (last) author was identified in 96.6% & was female in 18.3% of these. 130 prospective studies focused upon cancers that occur (almost) exclusively in women (breast, gyn); 51 focused upon cancers that occur exclusively among men (prostate, testicular, penile). Of the remaining 480 prospective studies, 453 (representing 603,132 participants) reported the sex distribution of participants; the mean percent female among these was 38.8%. Among these 453 studies, those with either first or senior female authors had a higher percentage female participants than studies with both male first and senior authors (mean 41.6% v 37.4%, p=.038). Government funding was reported in 43.9% of the non-sex-specific prospective studies. Among the non-sex-specific studies, the percent female participants was significantly higher in studies reporting government funding than others (mean 41.4% v 36.7%, p=.003). In a regression model, both government funding & female gender of the first or senior author were independent significant predictors of a higher percent of female participants (government funding: beta=.122, p<.01; female authorship: beta=.118, p<.012). Government funding & author gender explained a significant proportion of the variance in the percent of female participants (R2=.027, p<.001). Conclusion: Studies were more likely to include female participants when funded by the government and when authored by female investigators. No significant financial relationships to disclose.
Safety and efficacy of metronomic nonpegylated liposomal doxorubicin in heavily pretreated advanced breast cancer.
Authors: L. Manso
Journal: Journal of Clinical Oncology (2010)

1128 Background: Evidence suggest that cytotoxic agents may inhibit tumor growth through an antiangiogenic mechanism. Metronomic administration of the same chemotherapy agents at lower doses may optimize their antiangiogenic properties. Anthracyclines are the mainstay of therapy for breast cancer. Nonpegylated liposomal doxorubicin (TLC-D99) has demonstrated reduced cardiac toxicity, with antitumor responses comparable to those of conventional doxorubicin. Methods: Patients (n=26) with heavily pretreated advanced breast cancer were candidates to receive weekly fixed doses of cyclophosphamide (50 mg bid daily) plus nonpegylated liposomal doxorubicin (30 mg IV) plus 5FU (500 mg IV) plus vincristine (0.25 mg IV) plus prednisone (10 mg bid daily), CDFVP or Metronomic Cooper type regimen. A restrospective analysis was undertaken. Patients were previously treated with conventional anthracyclines in an adjuvant or metastatic setting. Results: In 26 heavily pretreated patients (> 4 lines of previous chemotherapy for advanced disease), we observed 5 partial responses (PR; 19%), 10 patients with stable disease (SD, 38%), and 11 patients with progressive disease (PD; 42%). The overall clinical benefit (PR+SD) was 57%. No complete response was found. Median time to progression was 12 weeks (95% CI; 8.3 to 15.7). Treatment was generally well tolerated with acceptable toxicity. Grade 3 or 4 hematologic adverse effects were neutropenia (n=7, 27%) and trombopenia (n=7, 27%). The most common nonhematologic adverse events were alopecia (n=16, 61%), asthenia (n=3, 11%) and nausea (n=3, 11%). No febrile neutropenia was found. None of the 26 patients presented cardiac toxicity. A reduction of LVEF<10% was observed in only one patient but did not require treatment interruption. Conclusions: Treatment with metronomic nonpegylated liposomal doxorubicin in combination with cyclophosphamide, 5FU, vincristine, and prednisone was effective in heavily preteated advanced breast cancer and was minimally toxic. No serious cardiac event was observed. No significant financial relationships to disclose.
A renal cancer cell (RENCA) vaccine successfully inhibits tumor induction and progression in a murine renal cancer model
Authors: C. Doehn, N. Esser, H.-G. Pauels, D. Jocham, J. Drevs
Journal: Journal of Clinical Oncology (2004)

2617 Background: Recently, we have demonstrated that an adjuvant renal tumor cell vaccine (aTL) is effective in reducing the risk of tumor progression in patients with renal cell carcinoma (RCC) following radical nephrectomy. However, this approach has not been confirmed in an animal model. In a murine renal cancer (RENCA) model we investigated the impact of a renal cancer cell vaccine (RENCA vaccine) on tumor induction and progression. Methods: There were 7 groups with 12 female BALB/c mice in each group. All animals received 5 vaccinations in 3-week intervals before tumor induction (subcapsular injection of 5x105 RENCA cells) and one vaccination 14 days afterwards. In each 3 groups mice received a RENCA vaccine (lysate of 1x106, 5x106 or 1x107 RENCA cells, production process comparable to that of aTL applied in humans) with or without co-incubation using Interferon-gamma. The control group was treated with solvent only. All mice were sacrificed on day 21 after tumor induction. Study criteria were animal welfare and growth, volume and weight of the tumor bearing kidney and number of lung metastases. Additionally, the induction of cytotoxic T cells was determined by a 51chromium-release assay. Results: Mice in the vaccine groups did not show relevant side effects from vaccination. After tumor induction body weight decreased in mice from the control group whereas it remained stable in the vaccine groups. All animals in the control group developed a renal tumor while in the vaccine groups 65/72 animals did not. The mean number of lung metastases was 100 (range 3–750) in the control group compared to 4 (range 0–196) in the vaccine groups. The 51chromium-release assay confirmed a significant activity of splenocytes from mice in the vaccine groups against RENCA cells compared to mice in the control group. Conclusions: We were able to demonstrate antitumor effects from treatment with a RENCA vaccine in a RENCA model. These findings may confirm the results from a recent phase III trial showing that an adjuvant renal tumor cell vaccine (aTL) is effective in reducing the risk of tumor progression in patients with RCC following radical nephrectomy. No significant financial relationships to disclose.
Alliance A091103: Multicenter phase II study of the angiopoietin-1 and -2 peptibody trebananib for the treatment of angiosarcoma.
Authors: Sandra P. D'Angelo, Michelle R. Mahoney, Brian Andrew Van Tine, Douglas Adkins, Maria T. Grosse Perdekamp, Mercedes M. Condy, Eliza Hartley, Cristina R. Antonescu, Gary K. Schwartz, William D. Tap
Journal: Journal of Clinical Oncology (2013)

TPS10592 Background: Angiosarcomas (ASs) are rare, aggressive, malignant endothelial cell tumors that constitute 1% to 2% of all soft tissue sarcomas with 5-year survival of 35%. Cytotoxic agents have demonstrated response rates of about 15%. Gene-array data from MSKCC has revealed up-regulation of endothelial associated genes, including active members of the angiopoietin system e.g., Tie2 and Angiopoietin 2 (Ang2). Trebananib (AMG386) is a novel agent that targets Ang1 and Ang2. We hypothesize that inhibition of angiopoietin 2 with trebananib will be an effective therapy in patients (pts) with AS. Methods: This CTEP sponsored, investigator initiated, multi-center phase II study uses trebananib, in pts with AS having metastatic/unresectable AS and conducted through the Alliance for Clinical Trials in Oncology (Alliance A091103). Pts must have adequate performance status, organ function, and measurable disease (RECIST v1.1). Patients are treated with trebananib 30mg/kg d1, 8, 15, and 22 every 28 days until either progressive disease or unacceptable toxicity. The primary endpoint is objective overall response rate (ORR) via RECIST v1.1. Secondary endpoints include the evaluation of progression-free survival (PFS) and overall survival (OS). Translational objectives include correlation of ORR, PFS and OS with i. baseline and post-treatment expression of Ang2 and Tie2 by immunohistochemistry (IHC), ii. serum levels of Ang1 and Ang2, iii. baseline and post-treatment phospho-receptor tyrosine kinase (p-RTK) status of Tie2, VEGFR-2, PI3K, MEK and MAPK, and iv. mutational status of VEGFR-2 and amplification of MYC/FLT4. A Simon Optimal two-stage phase II study design is used and one confirmed response in the first 12 pts expands enrollment to 25. Pre- and post-treatment biopsies will be performed in up to 10 pts treated at MSKCC. Enrollment began in July 2012. As of January 2013, 7 pts have been recruited. Clinicaltrials.gov#: NCT01623869. Funded by the Alliance Clinical Trials in Oncology. NIH Grant CA-25224. Clinical trial information: NCT01623869.
Phase I trial and pharmacokinetic (PK) study of ABT-751, an orally bioavailable tubulin binding agent, in pediatric patients with refractory solid tumors
Authors: S. Y. Cho, P. C. Adamson, A. E. Hagey, B. C. Widemann, J. M. Maris, E. Fox, D. Medina, Y. Cui, G. B. Gordon, F. M. Balis
Journal: Journal of Clinical Oncology (2004)

2080 Background: ABT-751 is an orally bioavailable sulfonamide that binds to the colchicine-binding site on β-tubulin and inhibits microtubule polymerization. The maximum tolerated dose (MTD) in adults is 250 mg on a daily x 7 days schedule and 200 mg on a daily x 21 schedule. The dose-limiting toxicities (DLT) are ileus and peripheral neuropathy. Methods: This Phase I trial in children with refractory solid tumors will determine the toxicity profile, DLTs, MTD, and PK of oral ABT-751 given once daily x 7 days, every 21 days, and given daily x 21 days every 28 days. A total of 22 subjects (median, 13 yr; range, 5–18 yr) have enrolled. For the 7-day schedule, the starting dose was 100 mg/m2/d (n=4) with escalations to 130 (n=6), 165 (n=6), and 200 (n=3) mg/m2/d. 3 subjects are enrolled on the first dose cohort in the daily x 21 days schedule at 75 mg/m2/d. Plasma and urine samples were collected over 24 h after dosing on Day 1 of the first cycle; ABT-751 and its major metabolites (sulfate and glucuronide) were determined by a validated LC-MS/MS assay. Results: DLTs include grade 2 motor neuropathy (bilateral wrist drop) in 1/6 patients at 130 mg/m2/d and grade 3 constipation in 1/6 patients at 165 mg/m2/d. Non-DLTs include sensory neuropathy, nausea, constipation, and transiently elevated serum transaminases. ABT-751 was rapidly absorbed (Tmax ∼ 2.6 h) and eliminated (t1/2∼ 6.1 h) and AUC increased proportionally with dose. A patient with neuroblastoma (NB) at 100 mg/m2/d has stable disease after >24 cycles, and a 2nd patient with NB at 165 mg/m2/d and disease limited to bone marrow and 123I-MIBG positivity had complete resolution of tumor in all previous disease sites after >14 cycles.Conclusions: ABT-751 is well-tolerated in children at doses exceeding the adult MTD. ABT-751 PK in children were similar to those previously observed in adults. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories Abbott Laboratories
UAB's experience with concurrent capecitabine (CAP) and radiotherapy (RT) in Pts with resected (RES) or locally advanced (LA) pancreatic cancer (Pan Ca)
Authors: M. Joseph, S. Russo, B. Plants, L. Ledbetter, J. Posey, S. Vickers, M. W. Saif
Journal: Journal of Clinical Oncology (2004)

4188 Introduction: Concurrent 5-FU-RT is the standard Rx for RES or LA Pan Ca. CAP is an attractive RT sensitizer due to tumor localization of thymidine phosphorylase (TP), oral administration, and relatively less toxicity. Purpose: To report our clinical experience with CAP-RT in Pan Ca from 04/02 - 09/03. Methods: 27 pts (11M, 16F; Median age: 64y; 6 RES, 21 LA; 25 Adeno, 2 Endocrine) received CAP (600–800mg/m2 PO BID M-F) with RT (5.4Gy) followed by 4-wk rest, then CAP 2500mg/m2 BID x 14d q 3 wks x 6 cycles for RES and until progression in LA dse. Pts were assessed wkly during CAP-RT and q 3 wks during CAP. Follow-up evaluations include toxicity, re-staging CT, and CA 19–9. Results: Median follow-up from time of completion of CAP-RT is 6.5m (1 - 12.5). By 9/30/03, 19 pts are alive and 8 dead with a median survival of 14m (4 - 16). 5 are alive with no evidence of dse (4 RES; 1 LA with resection). 6 are alive with stable dse. 5 LA pts underwent exploratory laparotomy 6 to 9m S/P CAP-RT. Operative findings showed response to Rx with extensive fibrosis, which prohibited all but 1 pt to be resected. 2 RES pts had recurrence in tumor bed. 4 LA pts had local progression within RT port, 3 had local progression with distant mets, and another 6 had distant mets only. Rx-related toxicity is summarized in Table 1. 5 pts developed GI bleeding within RT port as a late complication (3m S/P RT) while on CAP. 2 died from uncontrolled bleeding, 3rd responded to duodenal artery embolization, and 2 required occasional transfusions. Conclusion: There is no data comparing toxicity/efficacy of CAP-RT with 5-FU-RT. Our study shows that CAP-RT had favorable tumor response and survival in LA pts. Acute toxicities are manageable but GI bleeding could manifest as a late toxicity. We speculate that this may represent a “Radiation Recall” related to up-regulation of TP. We recommend caution during CAP therapy after CAP-RT. No significant financial relationships to disclose.
Poly(ADP-ribose) polymerase-1 (PARP-1) expression in patients treated with breast-conserving surgery and radiation therapy (BCS+RT).
Authors: J. Goswami, S. Goyal, H. Wu, M. S. Moran, B. G. Haffty
Journal: Journal of Clinical Oncology (2010)

582 Background: Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein involved in single- and double-stranded DNA break repair. PARP deficiency has been implicated in leading to the development of breast cancer as cells with damaged DNA accumulate. Meanwhile, PARP-1 inhibitors are being developed as a therapeutic option to increase sensitivity to DNA damaging agents. The purposes of this study were to examine PARP-1 expression in early stage breast cancer patients treated with breast-conservation surgery and radiotherapy (BCS+RT) and to determine the prognostic use of PARP-1 in this group of patients. Methods: Paraffin specimens from 504 women with early-stage breast cancer treated with BCT were constructed into a tissue micro-array (TMA). The TMA was stained for ER, PR, HER2, and PARP-1, and read as postitive or negative by a trained, blinded pathologist. Clinical-pathologic data, long term outcomes, and PARP-1 staining results were entered into a database for analysis. Results: PARP-1 expression was evaluable in 457 cases (80%). Staining was highly specific and PARP-1 was expressed in 5% of cases. Of the 457 cases, 61%, 55%, and 13% were ER+, PR+, and HER2+ respectively. Additionally, 24% of patients were triple-negative, PARP-1 over-expression correlated with age > 50 (p < 0.001) but not with race, T stage, N stage, ER, PR, or HER-2 status. PARP-1 over-expression led to significantly reduced cause-specific survival (p < 0.0002) and showed a trend of influencing overall survival (p = 0.1). PARP-1 expression did not correlate to ipsilateral breast tumor recurrence or loco-regional failure. Conclusions: To our knowledge this is the first study to assess the prognostic value of PARP-1 expression in a cohort of early-stage breast cancer patients treated with BCS+RT. We found PARP-1 to be predictive of cause-specific survival but not overall survival. Additional confirmation in larger datasets may elucidate the therapeutic role of PARP-1 inhibition. This research was supported by the Breast Cancer Research Foundation. No significant financial relationships to disclose.
Mtor Complex 1 Plays Critical Roles in Hematopoiesis and Pten-Loss-Evoked Leukemogenesis
Authors: Demetrios Kalaitzidis, Stephen M. Sykes, Natalie Punt, Yuefeng Tang, Steven W. Lane, Clary Clish, D. Gary Gilliland, David T. Scadden, David Guertin, Scott A. Armstrong
Journal: Blood (2011)
Quality of life (QOL) after long-term follow-up in patients with early breast cancer (EBC)
Authors: A. Lot, J. Hernandez, S. Delaloge, M. Spielmann, A. Dunant, M. Di Palma, P. Amiel, S. Dauchy, F. André
Journal: Journal of Clinical Oncology (2008)

20635 Background: Adjuvant anthracyclines-based chemotherapy is effective in EBC to improve the disease-free survival. The initial aim of this study was to assess the QOL of long-term survivors of early breast cancer, especially with regards to anthracycline therapy. Methods: Questionnaires were sent to women of one French hospital who had participated in two randomized trials comparing anthracyclines (CT group) with no chemotherapy (control group) in EBC, and who had no recurrence. Three self-evaluation QOL instruments were used (SF-36, QLQ-C30 and BR23) to compare QOL between the two treatment arms, and with the French general population. Comparisons with the French norms were standardised on sex and age. We selected a priori some scales of interest. All comparisons were made with a p value of 0.01. Results: 932 patients had been enrolled in the primary trials. Among them, 552 were eligible and 155 completed the questionnaires (77 patients in the CT group, 78 in the control group), 14 years on average after randomization. Their mean age at completion was 70 years. Age, tumor and non-chemotherapy treatment characteristics were equally balanced between CT and control group, and between responders and non responders. The two treatment groups did not differ significantly in the “physical functioning”, “social functioning”, “vitality”, and “physical and mental health summary” scales of the SF36 (with differences of 3 points maximum), in the “global QOL scale” of the QLQ (62 in CT group vs 67 in control group, p=0.11) and in the “future perspective” of the BR23 (61 vs 61, p=0.97). However, the 155 patients reported significantly lower SF36 scores than the French female norms for the “role limitation due to physical problems” (52 vs 65, p<0.0001) and “role limitation due to emotional problems” scales (53 vs 71, p<0.0001). Conclusions: This study did not detect any difference in long-term QOL that could be related to adjuvant chemotherapy in patients with breast cancer. Nevertheless, after a long-term follow-up, two a-priori defined parameters were significantly altered in patients who experienced breast cancer as compared to general population. This observation argues for a more in depth analysis of long-term QOL in breast cancer survivors. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer
Docetaxel and cisplatin as induction chemotherapy in stage IIIA N2 non-small cell lung cancer (NSCLC): An EORTC phase II trial (08984)
Authors: C. Manegold, B. Biesma, H. Smit, J. Van Meerbeeck, C. Debruyne, C. Legrand, G. Giaccone
Journal: Journal of Clinical Oncology (2004)

7166 Background: From January 2000 to August 2002, fourty-six chemo- and radiotherapy naïve patients (pts) with pathologically confirmed mediastinoscopy proven stage IIIa/N2 NSCLC were treated with induction Docetaxel and Cisplatin within a 2-stage phase II trial. Based on institutional policy, pts were registered for the EORTC 08941 trial comparing surgical resection with radical radiotherapy after chemotherapy (Splinter, 2000). Methods: Docetaxel was given at a dose of 85 mg/m2 on day 1 as a 1-hour infusion with premedication, followed by Cisplatin at a dose of 40 mg/m2/day given on day 1 and 2. Courses were repeated every 21 days and a maximum of 3 courses were given. Responses were evaluated according to the RECIST criteria. Results: Of the 46 patients registered, about 2/3rd (65.2 %) had a performance status of 0/1 and most of the patients were male (80.4 %). Median age was 60 years (range 27–74), and in the majority of patients the histological subtypes were squamous (43.5%) and adeno (34.8 %). The reported hematological grade 3/4 toxicities were as follows:leucopenia (21 pts), neutropenia (30 pts); there was no grade 3/4 thrombocytopenia or anemia. Eight cases of febrile neutropenia were reported of which one resulted in early death. Other common non-hematological toxicities CTC grade 3/4 were: nausea (8 pts), vomiting (6 pts), fatigue (5 pts) and dyspnoe (5 pts). 39/46 pts (84.8 %) reached the end of treatment as defined by the protocol, 6 pts (13 %) stopped due to toxicity and one pt due to protocol violation before reaching 3 cycles. Considering eligible pts (n=40), a total of 18 responses ( 1 CR and 17 PR) have been reported (RR 45 %; 95 % CI: 29.3 % - 61.5 %). The median survival of all pts was 16.7 months (95 % CI: 12.2 % -21.7 %), and the 1- year-survival rate was 64.6 % (95 % CI: 50.1–79.0). Conclusion: As a result of this international multi-center phase II trial the combination of Docetaxel and Cisplatin seems to be a tolerable and effective regimen for induction chemotherapy of stage IIIa/N2 NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis