tbuckley/cabot-search huggingface dataset:
Phase II clinical trial on docetaxel in the treatment of non-small-cell lung cancer (NSCLC)
Authors: Y. Chen, Y. Zhao, Z. Chen, M. Liao
Journal: Journal of Clinical Oncology (2005)

7352 Purpose: To investigate the efficacy and safety of Docetaxel plus cisplatin regiment every week and every 3 weeks in patents with non-small-cell lung cancer (NSCLC). Methods: Patients with NSCLC were divided into two groups. A group: randomly assigned to receive Docetaxel (Taxotere) 33mg/m2 d1, 8, 15 plus cisplatin 75mg/m2 d1 every 4 weeks. B group: Docetaxel 75mg/m2 d1 plus cisplatin 75mg/m2 d1 every 3 weeks. Results: 14 of patients were evaluable for efficacy. Overall response rates were 50%, group A and B were 40%, 55.5% respectively. Response rate of group B was higher than group A. The major toxicities were neutropenia, nausea, vomiting, alopecia. There was no grade IV bone marrow depression observed in two groups. Neutropenia was common with B than A (P>0.05). Grade IV singultus was observed in one patient and withdraw the study. Hypotension in 1 patient, BP was 90/60mmHg, recovered with treatment. Middle survival time of group A was 25.8 months, 24 months in group B. 1 year survival rate of group A was 100%, 84.6% in group B. Conclusion: Docetaxel plus cisplatin regimens are an effective and well-tolerated in patient with NSCLC. Response of group B was higher than group A, but 1 year survival rate of group A was higher than group B. No significant financial relationships to disclose.
Phase I study of dasatinib in combination with bevacizumab in advanced solid tumors.
Authors: G. Kim, C. M. Annunziata, G. A. Sarosy, L. M. Minasian, S. A. Prindiville, J. Zujewski, L. Otten, J. Squires, N. D. Houston, E. C. Kohn
Journal: Journal of Clinical Oncology (2010)

TPS163 Background: Despite the tremendous promise of new signal transduction and angiogenesis inhibitors, these targeted drugs have met with mixed results so far in the clinic. In solid tumors, inhibition of multiple targets may be necessary for significant clinical effects. Dasatinib is an inhibitor of all SRC-family kinases, as well as BCR-ABL, c-KIT, multiple EPH-family kinases, PDGFβ receptor and other tyrosine kinases. Bevacizumab is a humanized IgG1 monoclonal antibody that binds all biologically active isoforms of human vascular endothelial growth factor (VEGF) with high affinity. Attenuation of both c-Src and VEGF pathways simultaneously provides the potential for synergistic antitumor activity, as there is a extensive interaction between these pathways. VEGFR transmits its downstream signal through multiple pathways involving c-Src (including activation of the prosurvival FAK pathway). Alternatively, VEGF production is known to be Src-mediated (including via STAT5 signaling). Thus, inhibition of c-Src may block the VEGF angiogenic stimulus in at least two independent ways. As they have a largely non- overlapping toxicity profile, we have initiated a Phase I trial combining these two drugs. Methods: Objectives: Determine the safety and toxicity of the combination of dasatinib and bevacizumab. Determine biochemical changes in the src-FAK and src-PLC-g and VEGF signal transduction pathways in tumor and stromal cells in response to treatment at the MTD. Eligibility: Adults with histologically documented solid tumor malignancy that is metastatic or unresectable and for which standard curative therapies do not exist or are no longer effective. Design:This is an open-label phase I dose escalation study. Dasatanib will be orally administered daily and bevacizumab will be given intravenously every two weeks. At the MTD, pharmacodynamic endpoints related to signal transduction pathway alterations and tumor vascularity will be measured with tumor biopsies and DCE-MRI. Approximately 48 patients will be needed to achieve the objectives of the trial. No significant financial relationships to disclose.
Abstract 4037: Combining tyrosine kinase inhibitors and isoflavones to target metastatic activity in prostate cancer cells
Authors: Lori P. Rice, Christine Pampo, Sharon Lepler, Dietmar W. Siemann
Journal: Cancer Research (2014)

Abstract Background: Efforts to impede early steps in the metastatic cascade have led to the development of promising small molecule targeting agents. The purpose of this study was to evaluate the use of Src tyrosine kinase inhibitors known to interfere with cell migration and invasion, in combination with a cytostatic soy isoflavone extract (ISFs) on metastatic activity in prostate cancer cells. Methods: PC-3ML cells (a gift from A. Fatatis, Drexel University), and LNCaP cells treated with a Src inhibitor, ISFs, or a combination, were evaluated for clonogenic cell survival, cell cycle progression, and transwell migration and invasion activity. Results: Src inhibitors and ISFs induced an accumulation of cells in the G1 and G2/M phases of the cell cycle, respectively, with little change in cell viability or survival. Invasion studies with PC-3 ML and LNCaP cells suggest that ISFs can reduce metastatic activity by 39% and 35%, respectively. In addition, ISFs enhance the effectiveness of the Src inhibitors to reduce invasiveness. This may indicate that including ISFs in treatment regimens may allow a lower dose of the targeting agent to be used to achieve optimal response and decrease toxicity. Conclusions: In vitro studies suggested that combining a Src inhibitor and ISFs resulted in greater inhibition of metastatic activity than either alone. Citation Format: Lori P. Rice, Christine Pampo, Sharon Lepler, Dietmar W. Siemann. Combining tyrosine kinase inhibitors and isoflavones to target metastatic activity in prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4037. doi:10.1158/1538-7445.AM2014-4037
Ethnic neutropenia among women of European, African, and Caribbean backgrounds
Authors: V. R. Grann, N. Bowman, Y. Wei, M. Horwitz, C. Joseph, K. Abdul, K. Abdul, H. Barlatier, R. Sandoval, J. Jacobson, D. Hershman
Journal: Journal of Clinical Oncology (2007)

6587 Background: Black women are less likely than white women to receive complete chemotherapy for cancer. One reason for interruption of chemotherapy may be a patient's low white blood count (WBC) or absolute neutrophil count (ANC). In studies of white blood cell count (WBC) and race, white individuals’ WBC has been considered the standard, and 25–40% of non-Hispanic black individuals have been described as having “benign ethnic neutropenia.”. We therefore studied the prevalence and severity of ethnic neutropenia among women in six ethnic groups and of the association between neutropenia and serum cytokine and C-reactive protein (CRP) levels and neutrophil elastase (ELA2) polymorphisms. Methods: Following IRB approval, each participant provided a blood sample that was tested for WBC with differentials, cytokines and CRP levels, and ELA2 polymorphisms. We compared median WBC and ANC using Kruskal-Wallis tests. We used Fisher's exact tests to analyze association of severe neutropenia with ethnicity, cytokine and CRP levels, and ELA2 polymorphisms. Results: We enrolled 263 women 20–70 years old who had no cancer diagnosis.. As the table shows, median WBC and ANC differed by group; Dominicans had significantly higher median WBCs and ANCs than all other groups. Of 12 women with severe neutropenia (ANC = 1,500), none was Dominican or European-American. Subjects with a common upregulating ELA2 promoter polymorphism (C-199A) had lower ANC counts than other subjects. No associations were found between ANC counts and either cytokines or CRP levels. Conclusions: Median WBC and ANC and severe neutropenia were associated with ethnicity. Mild neutropenia is considered clinically benign, but because severe neutropenia may result in decreased doses or delays in chemotherapeutic treatment for malignancies, ethnic neutropenia and its role in treatment decisions requires further investigation. No significant financial relationships to disclose. [Table: see text]
Definitive Results of a Phase II Trial of Cisplatin, Epirubicin, Continuous-Infusion Fluorouracil, and Gemcitabine in Stage IV Pancreatic Adenocarcinoma
Authors: M. Reni, P. Passoni, M. G. Panucci, R. Nicoletti, L. Galli, G. Balzano, A. Zerbi, V. Di Carlo, E. Villa
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To evaluate the efficacy and toxicity of a cisplatin, epirubicin, gemcitabine, and fluorouracil (PEF-G) schedule on stage IV pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients ≤ 70 years, with no prior chemotherapy and with bidimensionally measurable stage IV pancreatic adenocarcinoma, Eastern Cooperative Oncology Group performance status ≤ 2, and adequate bone marrow, kidney, and liver function were eligible for this trial. Eligibility criteria for clinical benefit assessment were pain with at least a daily analgesic consumption of two nonsteroidal anti-inflammatory drugs or Karnofsky performance status between 50 and 70. Treatment consisted of 40 mg/m 2 each of cisplatin and epirubicin day 1, gemcitabine 600 mg/m 2 on days 1 and 8 every 4 weeks, and fluorouracil 200 mg/m 2 /d as a protracted venous infusion. RESULTS: Between April 1997 and April 1999, 49 patients from a single institution were eligible for the study. Altogether, 203 cycles (median, four cycles) of PEF-G were delivered. The objective response rate was 58% in 43 assessable patients and 51% in the intent-to-treat population. Fourteen patients had stable disease. Grade 3 or 4 World Health Organization neutropenia occurred in 51% of cycles, thrombocytopenia in 28%, anemia in 7%, stomatitis in 5%, and diarrhea, and nausea, and vomiting in 2%. The median duration of response was 8.5 months. The median time to tumor progression was 7.5 months. The median survival was 11 months in the assessable population and 10 months in the intent-to-treat population. Clinical benefit was achieved in 22 (78%) of 28 assessable patients. CONCLUSION: PEF-G is a well-tolerated and safe regimen; it obtained a very high rate of durable responses and deserves further evaluation in a phase III trial.
Lenalidomide in relapsed adult T-cell leukaemia-lymphoma or peripheral T-cell lymphoma (ATLL-001): a phase 1, multicentre, dose-escalation study
Authors: Michinori Ogura, Yoshitaka Imaizumi, Naokuni Uike, Norio Asou, Atae Utsunomiya, Toshiki Uchida, Tomohiro Aoki, Kunihiro Tsukasaki, Jun Taguchi, Ilseung Choi, Dai Maruyama, Kisato Nosaka, Nianhang Chen, Shuichi Midorikawa, Tomoko Ohtsu, Kensei Tobinai
Journal: The Lancet Haematology (2016)
Low-dose radiation therapy and reduced chemotherapy in childhood Hodgkin's disease: the experience of the French Society of Pediatric Oncology.
Authors: O Oberlin, G Leverger, H Pacquement, M A Raquin, A Chompret, J L Habrand, M J Terrier-Lacombe, P Bey, Y Bertrand, H Rubie
Journal: Journal of Clinical Oncology (1992)

PURPOSE With the aim of decreasing undesirable side effects of therapy, we investigated the reduction of both chemotherapy and radiation therapy (RT) in children with Hodgkin's disease, and compared Adriamycin (doxorubicin; Farmitalia Carlo Erba, Rueil-Malmaison, France), bleomycin, vinblastine, and dacarbazine (ABVD) alone to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and ABVD in favorable cases and assessed the effectiveness of low-dose RT (20 Gy) after good response to chemotherapy. PATIENTS AND METHODS A French national study began in 1982 that included 238 pediatric patients with Hodgkin's disease. Initial staging was clinical and without laparotomy. In patients with localized disease (IA-IIA), an equivalence trial compared the effectiveness of four cycles of ABVD with two cycles of ABVD that were alternated with two cycles of MOPP. Patients with more advanced disease (IB-IIB-III-IV) received three courses of MOPP that was alternated with three courses of ABVD. All of the patients who achieved a good remission after chemotherapy were administered 20 Gy RT, which was limited to the initially involved areas for localized disease, and encompassed the paraaortic nodes and the spleen as well for more advanced stages. When a good remission was not obtained, 40 Gy RT was administered. RESULTS At the completion of chemotherapy, 227 patients (97%) were considered good responders, whereas 11 did not achieve a good remission. With a median follow-up of 6 years, the 6-year actuarial survival was 92% and the disease-free survival was 86%. The relapse-free survival in favorable stages was 90% in the ABVD arm and was 87% in the MOPP and ABVD arm. In June 1987, inclusion of stage IV patients was discontinued because of poor results. CONCLUSIONS Present findings indicate that (1) in favorable stages, ABVD alone and alternating MOPP and ABVD are equivalent, and (2) chemotherapy followed by 20 Gy RT represents a valid therapeutic approach in the vast majority of children with Hodgkin's disease.
Non-clinical factors associated with intentionally reduced breast cancer chemotherapy doses
Authors: E. Culakova, J. J. Griggs, M. E. Sorbero, D. A. Wolff, M. S. Poniewierski, G. H. Lyman
Journal: Journal of Clinical Oncology (2006)

6020 Background: Breast cancer survival and case-fatality rates are lower in women of lower socioeconomic status (SES) compared to those of higher SES. Disparities in the quality of chemotherapy may contribute to poorer outcomes among women of lower SES. The purpose of this study was to investigate the relation between SES (as measured by both individual and area-level characteristics) and the use of intentionally reduced breast cancer adjuvant chemotherapy doses. Methods: The cohort consisted of 764 breast cancer patients treated with a standard adjuvant chemotherapy regimen for stages I, II, or III enrolled in an IRB approved prospective registry. Information was collected on patient, disease, and treatment characteristics, including chemotherapy doses. Zip code level data on median household income (MHI), and proportions of residents with a high school (HS) or college degree were obtained from the US 2000 Census. Doses for cycle 1 of chemotherapy &lt; 85% of standard were considered to be reduced. Multivariate logistic regression analysis was performed to identify factors associated with the use of reduced first cycle doses. Results: In bivariate analysis, body mass index (BMI) (P=.003), education (P=.002), and region (P &lt; .001) were associated with the use of reduced doses. Race was borderline significant (P=.056). Reduced doses were more commonly administered to patients who lived in zip codes with lower MHI (P &lt; .001), lower education (P=.006), and higher levels of poverty (P &lt; .001). Age, stage, comorbidity, hormone receptor status, insurance, occupation, employment and marital status were not associated with use of reduced doses. In multivariate analysis without practice effects, high BMI (P &lt; .001), education less than HS (P=.009), and geographic region (P &lt; .001) were independently associated with reduced doses. The effect of BMI (P &lt; .001) stayed significant after adjustment for practice site, but education (P=.082) and geographic region (P=.127) became less so. Conclusions: Non-clinical factors, such as educational attainment and area level income, are associated with intentionally reduced doses of adjuvant chemotherapy. Interventions directed at improving quality of chemotherapy may improve breast cancer outcomes in patients of lower SES. No significant financial relationships to disclose.
Response patterns in children and adolescents exploited through sex rings and pornography
Authors: A W Burgess, C R Hartman, M P McCausland, P Powers
Journal: American Journal of Psychiatry (1984)

A study of 66 children and adolescents exploited by adults through sex rings and pornography shows that three-fourths of the victims demonstrated patterns of negative psychological and social adjustment after the rings were exposed. More than 61% of the victims had been ring members for more than a year and slightly more than half of the victims had been used in pornographic photographs. Victims who integrated the exploitation were those who had spent the least amount of time in the ring and who were least likely to have been involved in pornography. Boys were the sexual preference of the adult male ringleaders.
Cisplatin plus gemcitabine with or without vinorelbine as neo-adjuvant therapy for radically treatable stage III non-small cell lung cancer. Results of a randomised study of the Grupo Oncológico del Norte de España
Authors: E. Esteban, N. Villanueva, I. Muñiz, J. De Sande, J. Fra, Y. Fernández, J. Vieitez, M. Luque, P. Jimenez, J. Buesa, A. Lacave
Journal: Journal of Clinical Oncology (2006)

7121 The combinations of cisplatin (C) with gemcitabine (G) and/or vinorelbine (V) have shown to be effective and safe regimens in the first line treatment of NSCLC. This study has been designed to detect a 25% increase in objective response measured by CT scan with the triplet combination (CGV) with respect to cisplatin/gemcitabine combination (CG) administered as neo-adjuvant therapy in patients with radically-treatable stage III NSCLC. With 80% of power and one-sided 5% significant level, the simple size required to confirm this hypothesis is 75 evaluable patients in each arm of treatment. Patients (pts) ≤ 75 years old, Karnofsky index ≥ 70% and adequate haematological, renal and hepatic function are stratified by stage (IIIA versus IIIB) and randomly assigned to: C 50 mg/m 2 i.v. and G 1250 mg/m 2 i.v. d1 and d8 alone (CG) or in combination with V 25 mg/m 2 i.v. d1 and d8 (CGV) both regimens every 3 weeks for 3 consecutive cycles followed by definitive local treatment (LT). From December 1999 to December 2005, a hundred and forty-nine pts have been randomised (CG/CGV); median age 58/58; median Karnofsky index 80/80; stage IIIA 24/26; stage IIIB 51/48; squamous 37/39; adenocarcinoma 31/32; anaplastic 7/3. Major haematological toxicities grade 3–4 were (CG/CGV; %); Anaemia (5/5) neutropenia (31/34); thrombocytopenia (4/5). Two pts in CG (2.7%) and 4 in CGV arm (5.5%) developed neutropenic fever. Major non-haematological toxicities grade 2–3 were: N/Vomiting (31/32) and fatigue (12/20). Global recurrences have been registered in 57% and 54% of pts treated with CG and CGV arm respectively. Exclusive local/ distant failure (%) has been 16/23 in CG and 23/18 in CGV arm. Preliminary results show similar high efficacy associated with moderate toxicity in both groups of treatment. The study is continuing. [Table: see text] No significant financial relationships to disclose.
Examining disparities in colon cancer treatment patterns
Authors: D. M. Hynes, E. Tarlov, T. Lee, R. Perrin, Q. Zhang, M. Ferreira, R. A. Durazo-Arvizu, A. B. Benson III, D. J. Bentrem, C. L. Bennett
Journal: Journal of Clinical Oncology (2008)

6534 Background: Disparities in colon cancer treatment are a national concern, as they are among veterans in particular. Through agreements with eight National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program registries, we linked cancer registry, Medicare, and VA data to examine disparities in colon cancer treatment patterns. Methods: We identified a cohort of colon cancer patients from eight SEER registries who were diagnosed between 1999 and 2001 at age 66 or older and were eligible for VA and Medicare-funded care. We tracked care through 2004 and examined surgery and chemotherapy use and trends in one-year mortality. We used regression models to examine the relationship between age and race/ethnicity and adjuvant chemotherapy use. Results: Among the 2,027 veterans identified with colon cancer, 95% were male; 14% were African American; 17% were diagnosed at a VA facility; 1,788 (88%) underwent colectomy; 358 (20%) underwent colectomy at a VA facility. The one-year mortality rate was 28% overall. Among the 1,788 patients who underwent colectomy, prevalence of chemotherapy use was 9%, 27%, 58%, and 48% in stages I to IV, respectively (p-value <0.0001). Among the 1,074 stage II and III colectomy patients for whom hospital type (VA vs. non-VA) was known, a regression analysis controlling for comorbidity, stage, geographic region, and hospital type revealed that African Americans were less likely than non-African Americans (OR 0.54, CI: 0.34–0.84) and patients age 76-to-85 years and those 86 years or older were less likely than those age 66-to-75 years (OR 0.38, CI: 0.29–0.51 and OR 0.08, CI: 0.03–0.18, respectively) to receive adjuvant chemotherapy. We also found that veterans who underwent colectomy at a non-VA facility were more likely to receive adjuvant chemotherapy (OR 1.78, CI: 1.23–2.58). Conclusions: Among veterans with colon cancer identified in eight SEER registries, older and African American patients were less likely to receive chemotherapy even when stage, comorbidity, and geography were considered. Adherence to adjuvant chemotherapy guidelines among patients treated in VA hospitals warrants additional research. Efforts to better understand and address apparent disparities in colon cancer care are urgently needed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Department of Veterans Affairs
Renal dysfunction associated with the administration of high-dose interleukin-2 in 199 consecutive patients with metastatic melanoma or renal carcinoma.
Authors: A S Guleria, J C Yang, S L Topalian, J S Weber, D R Parkinson, M P MacFarlane, R L White, S M Steinberg, D E White, J H Einhorn
Journal: Journal of Clinical Oncology (1994)

PURPOSE To describe the incidence and management of renal dysfunction associated with the use of high-dose interleukin-2 (IL-2) (as is currently approved) in the treatment of cancer patients. PATIENTS AND METHODS One hundred ninety-nine consecutive patients with metastatic renal carcinoma or melanoma were treated with intravenous bolus infusions of IL-2 alone (720,000 IU/kg) every 8 hours. RESULTS Patients received 310 courses (589 cycles) of therapy and most experienced oliguria, hypotension, and weight gain; 13% of cycles were discontinued due to increased serum creatinine levels. Creatinine values (mean pretherapy, 1.2 mg/dL) increased during therapy and peaked (mean, 2.7 mg/dL) approximately 1 day after discontinuation of the second cycle of IL-2. Off therapy, toxicities reversed promptly and creatinine values returned to baseline. Higher peak creatinine values occurred in patients with renal carcinoma (v melanoma), older patients, males (v females), and those who had undergone prior nephrectomy. These same patient subsets received fewer doses of IL-2, but clinical responses were not associated with creatinine values or number of IL-2 doses administered. Urinalyses showed the appearance of protein, bilirubin, RBCs, WBCs, and granular casts during therapy, which cleared completely on follow-up evaluation. CONCLUSION High-dose IL-2 can be safely administered to cancer patients. The associated renal dysfunction is transient and without evidence of intrinsic long-term renal damage. Practical guidelines for patient management have been identified.