tbuckley/cabot-search huggingface dataset:
Capecitabine plus gemcitabine in thymic epithelial tumors: Final analysis of a phase II trial.
Authors: Carlo Buonerba, Margaret Ottaviano, Piera Federico, Filomena Calabrese, Claudia Von Arx, Simona Iaccarino, Lucia Nappi, Irene Tucci, Giuseppe di Lorenzo, Elide Matano, Vincenzo Damiano, Giovannella Palmieri
Journal: Journal of Clinical Oncology (2014)

7528 Background: Thymic epithelial tumors (TETs) are rare malignancies, with an estimated incidence of about 3 cases per 100,000 inhabitants. No standard treatment is available for recurrent disease. In 2005, a multi-institutional phase II trial was started on the combination of gemcitabine and capecitabine in pretreated patients with TETs. Final results of this phase II study are presented. Methods: Eligibility criteria for the study were mainly the following: histologic diagnosis of TET by central review; at least one prior systemic chemotherapy treatment; progressive disease. Treatment consisted of oral capecitabine (650 mg/mq twice daily on days 1–14) and i.v. gemcitabine (1000 mg/mq on days 1 and 8) every 3 weeks. The radiographic response rate was chosen as primary end point and employed to calculate the study sample. Secondary end points were progression-free survival, toxicity, and overall survival. Results: Thirty patients (18 men, 12 women; median age 57 years, range 48–61 years)were enrolled in this phase II trial from November, 2005 to June 2013. The majority of patients (73%) had thymoma, while the remaining had thymic carcinoma.Of note, 63% of patients showed disease progression within 2 months from the last dose of the last systemic therapy received. The most important grade 3 toxicity was neutropenia in eight patients. Twelve patients had a response (three complete responses and eight partial responses). Among thymic carcinoma patients, we observed three partial responses. Median PFS was 11 months (95% CI 3–17 months). The PFS for patients with thymoma and thymic carcinoma was 11 months (95% CI 6–17 months) and 6 months (95% CI 3–11 months), respectively. Thirteen patients are dead at the time of the analysis (median OS, 16 months). Conclusions: Capecitabine and gemcitabine is a highly active combination therapy in thymic epithelial tumors and should be routinely included in the managment of recurrent/metastatic disease.
Phase II study of pazopanib and weekly paclitaxel in metastatic or locally advanced squamous penile carcinoma patients previously treated with cisplatin-based chemotherapy: PAZOPEN study.
Authors: Miguel Angel Climent, Javier Puente, Sergio Vazquez-Estevez, María José Méndez-Vidal, Enrique Gonzalez-Billalabeitia, Nuria Laínez, José Pablo Maroto Rey, Juan Francisco Rodriguez-Moreno, Xavier Garcia del Muro
Journal: Journal of Clinical Oncology (2015)

TPS4584 Background: Metastatic or locally advanced squamous penile carcinoma (MLASPC) is an infrequent disease, with extremely bad prognosis. Platinum based chemotherapy is the most active treatment with a response rate (RR) of 30% and only 12 months of overall survival. New active agents are urgently needed. The combination of the antiangiogenic agent Pazopanib and paclitaxel have been tested in transitional carcinoma and melanoma with high number of responses and good tolerance profile. The aim of this study is to test the activity and safety of the combination in patients (pts) with MLASPC progressing to platinum based regimens. Methods: Phase II open label, single arm, multicentre study. Main inclusion criteria are: diagnosis of squamous penile carcinoma, ECOG 0-1, measurable disease by RECIST criteria, progressive disease after previous platinum based treatment, either in neoadyuvant, adyuvant or metastatic setting, adequate hepatic, renal and haematological function. Patients will receive treatment with pazopanib 800 mg p.o daily and paclitaxel 65 mg/m2/weekly D1, 8 and 15 every four weeks cycle. Main objective is RR (complete (CR) and partial response (PR) measured by RECIST criteria). Secondary objectives: Clinical benefit rate, (CR+ PR + SD), progression-free survival, response duration, overall survival, toxicity and tolerance profile. Whole exome sequencing will be performed to describe most frequent alterations in penile cancer. This is a two stage Simon optimal design for phase II trials. Considering an estimated 30% RR with P0 = 10%, (alpha error 5%, beta 20%), 10 patients will be included in first stage and if 2 or more responses are observed, then 19 additional patients will be included in second stage. If more than 5 responses are observed efficacy of treatment will be considered. The sample size, taking into account a 10% drop out rate will be 32 pts. Trial will be performed in 8 hospital centres of the SOGUG group. Study has been approved by ethic committees and health authorities. Funded by a grant from GlaxoSmithKline. NCT02279576. Clinical trial information: NCT02279576.
Second-line therapies in patients with KRAS wild-type metastatic colorectal cancer (mCRC) after first-line therapy with FOLFIRI in combination with cetuximab or bevacizumab in the AIO KRK0306 (FIRE 3) trial.
Authors: Dominik Paul Modest, Sebastian Stintzing, Ludwig Fischer Von Weikersthal, Thomas Decker, Alexander Kiani, Ursula Vehling-Kaiser, Salah-Eddin Al-Batran, Tobias Heintges, Christian A. Lerchenmuller, Christoph Kahl, Gernot Seipelt, Frank Kullmann, Martina Stauch, Werner Scheithauer, Swantje Held, Clemens Albrecht Giessen, Andreas Jung, Thomas Kirchner, Volker Heinemann
Journal: Journal of Clinical Oncology (2014)

3558^ Background: AIO KRK0306 (FIRE 3) trial compared first-line therapy with FOLFIRI plus either cetuximab (arm A) or bevacizumab (arm B) in 592 patients with KRAS exon 2 wild-type metastatic colorectal cancer (mCRC). We investigated choice and duration of second-line therapies, as well as overall survival (OS) and OS from beginning of second-line therapy according to second-line treatment. Methods: The protocol recommended second-line therapy with FOLFOX plus bevacizumab vs. irinotecan plus cetuximab in arm A vs. B, but physician were free to choose any regimen. second-line treatment was defined as any new anticancer drug for mCRC following first-line therapy. Duration of second-line therapy was calculated as time from first to last application of second-line treatment. Results: There were 260/297 patients in arm A and 250/295 patients in arm B who were alive after first-line therapy. Of those, 78.5% of patients arm A and 76.4% in arm B received second-line therapy so far. First-line progression free survival (PFS) according to second-line antibody use was associated with 9.2 (anti-vascular endothelial growth factor [VEGF]), comparing to 9.7 (anti-epidermal growth factor receptor [EGFR]) and 11.3 months (no mAB); p=0.001. Correspondingly, OS was 25.2 (anti-VEGF) vs. 23.7 (anti-EGFR) vs. 30.8 months (no mAB), p=0.02. First-line PFS according to seconnd-line oxaliplatin (Ox) use was associated with 9.9 (Ox), comparing to 9.9 months (no Ox); p=0.56. OS according to Ox-use was 27.1 (ox) vs. 29.1 months (no Ox); p=0.10. 2nd-line therapy was administered for a median of 17.2 weeks in arm A and 14.0 weeks in arm b (p=0.08). Second-line regimens with antibody-crossover were administered for a median of 23.9 weeks in arm A and 16.1 weeks arm B (p=0.06). Updated results might be presented at the annual meeting. Conclusions: This retrospective analysis indicates that second-line application of antibodies was favoured in patients with shorter first-line PFS, suggesting that preplanned second-line therapy may not reflect therapeutic reality. Correspondingly, second-line treatment without antibodies compared to antibody-based regimens was associated with longer OS. A trend towards longer second-line therapy was observed in favour of patients receiving cetuximab as first-line therapy. Clinical trial information: NCT00433927.
Nab-paclitaxel and gemcitabine in advanced pancreatic cancer: The one-year experience of the National Cancer Institute of Naples.
Authors: Alessandro Ottaiano, Monica Capozzi, Chiara De Divitiis, Claudia Von Arx, Elena Di Girolamo, Guglielmo Nasti, Ernesta Cavalcanti, Fabiana Tatangelo, Giovanni Romano, Salvatore Tafuto
Journal: Journal of Clinical Oncology (2017)

497 Background: Pancreas adenocarcinoma is the sixth cause of cancer-related death worldwide and the mortality is increasing in the Western Countries. Recently, the association between nab-paclitaxel (nab-P) and gemcitabine (GEM) has significantly improved progression-free (PFS) and overall survival (OS) compared to GEM monotherapy (PFS: 5.5 vs 3.7 months; OS: 8.5 vs 6.7 months). Methods: Patients affected by metastatic pancreas adenocarcinoma were treated at the Department of Abdominal Oncology of the National Cancer Institute of Naples from July 2015 to July 2016 with nab-P at 125 mg per square meter of body-surface area followed by GEM at 1000 mg per square meter on days 1, 8, and 15 every 4 weeks. Computed tomography (CT) was done every three months of therapy. Toxicity was graded with NCI-CTC criteria v4.0. Objective responses were evaluated with RECIST. Analysis of time-to-progression is only descriptive. Pain was evaluated with a visual analogic scale. Results: Twenty-three patients were treated. Median age was 67 years (range: 45-81); 8 patients were ≥ 70 years old. Performance Status (PS) ECOG was 2 in 8 patients, 1 in 10 and 0 in 5. Twelve patients presented with diffuse hepatic metastases, 4 with carcinosis, 7 with more than one organ involvement. They received a median number of 13 administrations (range: 3-32) of therapy. During therapy Nab-P was reduced at 100 mg per square meter in all patients. The most common G3/G4 adverse events were neutropenia (13.0% G4, 8.6% G3, none was febrile), neuropathy (30.4% G3) and asthenia (G3 17.3%). The disease control rate was 43.4% (PR+SD 10/23); PR was registered in three patients (response rate: 13.0%). Twelve patients progressed and seven dead at September 20. The median time-to-progression was 7.9 months (95% confidence interval 5.8-11.2). After three months of therapy the PS improved in 14 patients as well as pain in 18 patients. Conclusions: We present an experience with nab-P and GEM association in a series with poor PS and highly metastatic disease relatively to the previous randomized study. The schedule is feasible with nab-P at 100 mg per square meter and it achieves a good disease control rate as well as a clinical benefit.
Social inequality in survival after lung cancer: The attribution of stage at diagnosis, receipt of treatment, and comorbidity in a Danish nationwide clinical database study.
Authors: Susanne O. Dalton, Marianne Steding-Jessen, Erik Jakobsen, Joachim Schuz, Christoffer Johansen
Journal: Journal of Clinical Oncology (2013)

6570 Background: Survival after lung cancer depends on stage, treatment, and patient-specific factors as comorbidity. These factors are potentially influenced by social position (SEP). We previously reported a lower risk for advanced-stage lung cancer among persons with higher SEP and we investigate the association between SEP (education, income and cohabiting status) on receipt of 1 st line treatment and overall survival in a population-based cohort of lung cancer patients in Denmark. Methods: This registry-based cohort study links data on prognostic factors and treatment from the Danish Lung Cancer Registry to individual socioeconomic information in Statistics Denmark and comorbidity from the National Hospital Discharge Registry for 13,659 persons diagnosed with lung cancer 2004-2011. Results: ORs for receipt of 1 st line treatment were higher with longer education and higher income and for patients living with a partner in both men and women with low (T1-3N0M0; T0-3N1M0) and advanced-stage (T0-3N2-3M0; T4N0-3M0; TxNxM1) lung cancer although not statistically significant for all estimates. Among low-stage patients all-cause mortality was 15% higher in patients with short vs higher education, 26% higher for low vs high income and 23% higher for living alone vs living with a partner. In advanced-stage patients, differences in all-cause mortality was 11%, 14% and 8% for education, income and cohabitation status. Stage, treatment, Charlson Comorbidity Score and Performance Score attenuated associations but did not eliminate the association between low income (HR, 1.12; 95% CI, 1.05-1.19) and living alone (HR, 1.15; 95 CI, 1.06-1.25) in low stage lung cancer patients while no social differences in adjusted HR remained in advanced-stage patients. Conclusions: We show that even in a country with free and equal access to health care disparities exist in access to lung cancer treatment both of curative and of palliative intent. Differences in stage, treatment and presence of comorbidity by social position explained most of the social inequality in lung cancer survival although differences remained in the short term for low-stage patients.
Effect of 12-week home-based exercise program on fasting insulin in stage II-III colorectal cancer survivors: A randomized controlled trial.
Authors: MI KYUNG LEE, Ji Young Kim, Ji-Hye Park, Junga Lee, Dong-il Kim, Dongwoo Kang, Minsuk Oh, Ki-Yong An, Ji-Won Lee, Sanghui Chu, Nam Kyu Kim, Jeffrey A. Meyerhardt, Lee Jones, Justin Y Jeon
Journal: Journal of Clinical Oncology (2014)

3588 Background: High insulin levels may be associated with an increased risk of colorectal cancer (CRC) development and recurrence. However, the effect of exercise on fasting insulin level in colorectal cancer survivors has not been fully studied. We conducted a randomized control trial to determine the effect of a 12-week home based exercise program on fasting insulin, body composition, and fitness in stage II-III CRC survivors. Methods: 123 stage II-III CRC survivors between 4 and 102 weeks after standard cancer therapy (surgery, chemotherapy, and/or radiation therapy) were randomly assigned to either the 12-week home-based exercise (n=62) or usual care (n=61) group. The goal of the home-based exercise was to increase the level of physical activity of the participants to 18-27 MET hours per week. The primary outcome measurement was fasting insulin and secondary outcome measurements were body composition and fitness level. Results: A total of 99 (80.5%) participants completed the trial. After 12 week of home-based exercise program, fasting insulin level was significantly reduced in exercise group while it did not change in control group (Ex, 6.09±3.96 vs. 4.93±3.41 µU/ml; Con, 6.74±3.40 vs. 6.73±3.01 µU/ml, between group p=0.045). Furthermore, percent body fat was significantly reduced (Ex, 27.53±8.59 vs. 26.83±8.41%; Con, 27.18±7.02 vs. 27.85±7.11 %, between group p=0.033), and 6-min walk test (Ex, 580.72±82.09 vs. 611.54±74.51 m; Con, 598.06±65.03 vs. 606.03±58.26 m, between group p=0.041), Chair Stand test (Ex, 19.71±6.53 vs. 23.08±5.06; Con, 23.87±6.20 vs. 23.83±4.31, between group p=0.004), and push up (Ex, 15.21±9.68 vs. 20.89±11.83; Con, 15.44±13.03 vs. 12.59±10.98, between group p <0.000) were significantly improved in exercise group. Conclusions: The 12-week home based exercise intervention decreased fasting insulin and percent body fat, and improved fitness in stage II-III CRC survivors. The current study was supported by the National Research Foundation of Korea (2013K2A1A2054437) and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (1120230).
Investing in a novel shorter treatment regimen for multidrug-resistant tuberculosis: to be repeated
Authors: Mohammed A. Yassin, Ernesto Jaramillo, Eliud Wandwalo, Dennis Falzon, Anna Scardigli, Osamu Kunii, Karin Weyer
Journal: European Respiratory Journal (2017)

Tuberculosis (TB) patients with multidrug-resistant (resistance to isoniazid and rifampicin) (MDR-TB) or rifampicin-resistant strains (MDR/RR-TB) do not respond to the standardised first-line TB regimen which is highly effective in other TB patients, requiring much longer and toxic second-line treatment [1]. In fact, only about a half of all MDR/RR-TB patients placed on these regimens worldwide complete them successfully, attesting to the difficulties in scaling up such regimens satisfactorily [2]. Even if only about 4% of new TB patients globally have MDR/RR-TB, they account for over half a million new individuals annually, challenging the constrained resources available for TB care in the low- and middle-income countries where most of them live. Donor support of innovative interventions such as operational research can reap rapid benefits for TB control <http://ow.ly/wcXM3091P9H> Authors’ contributions: all authors contributed substantively to the ideation and writing of the manuscript and approved its final version. M.A. Yassin, E. Wandwalo, A. Scardigli and O. Kunii are staff members of the Global Fund to Fight AIDS, Tuberculosis and Malaria. D. Falzon, E. Jaramillo and K. Weyer are staff members of the World Health Organization. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions or policies of WHO and the Global Fund.
A multicenter, randomized, double-blind, phase III study of ramucirumab (IMC-1121B; RAM) and best supportive care (BSC) versus placebo (PBO) and BSC as second-line treatment in patients (pts) with hepatocellular carcinoma (HCC) following first-line therapy with sorafenib (SOR).
Authors: Andrew X. Zhu, Ian Chau, Jean-Frédéric Blanc, Takuji Okusaka, Maria Rojas, Ling Yang, Ingo Von Broen
Journal: Journal of Clinical Oncology (2012)

TPS4146 Background: Blockade of vascular endothelial growth factor (VEGF) signaling in HCC has been shown in preclinical models with monoclonal antibodies and small molecule multikinase inhibitors, and in clinical trials with SOR, to have anti-tumor activity and improve survival. RAM, a fully human monoclonal antibody, binds to the VEGF receptor-2 (VEGFR-2), potently blocks the binding of the VEGF ligand to VEGFR-2, inhibits VEGF-stimulated activation of VEGFR-2, and neutralizes VEGF-induced mitogenesis of human endothelial cells. In a single-arm, Phase 2 study of RAM as 1st-line monotherapy in 42 pts with advanced HCC (Zhu, ILCA 2010, abstr. O-033), preliminary results included median progression-free survival (PFS) of 4 months (m), time to progression (TTP) of 4.2 m, overall survival (OS) of 12 m and disease control rate of 70% (best overall response: 10% partial response, 60% stable disease). Methods: Pts with HCC with disease progression during or following 1st-line therapy with SOR (or who were intolerant to SOR) are randomized 1:1 to receive RAM (8 mg/kg) or PBO once every 2 weeks, with BSC, until disease progression or intolerable toxicity. Eligibility includes prior SOR as 1st-line systemic treatment for HCC, Child-Pugh A, B7 or 8 cirrhosis, ECOG PS 0-1, bilirubin &lt; 3 mg/dL, transaminases ≤ 5 × upper limit of normal (ULN), creatinine ≤ 1.2 × ULN, and platelets ≥ 75×10 3 /µL. The primary endpoint is OS. Secondary endpoints include PFS, best objective response rate, TTP, patient-reported outcome measures of disease-specific symptoms and health-related quality of life, safety, and RAM pharmacokinetics, pharmacodynamics, and immunogenicity. With 544 patients, this study is designed to detect an increase in OS (median 6 m with PBO to 8 m with RAM; 1-sided α= 2.5%, 85% power). As of 18 January 2012, approximately 52% of planned pts have been randomized. The IDMC reviewed this study on 21 June and 3 November 2011 and recommended the study to continue unmodified.
Financial burden of cancer clinical trials: Impact of an equity program intervention.
Authors: Ryan David Nipp, Daniel Finkelstein, Elizabeth Powell, Lisa Vittorio, Nicole Birrer, Bruce Allan Chabner, Hang Lee, Beverly Moy
Journal: Journal of Clinical Oncology (2015)

6501 Background: Cancer patients (pts) often experience financial burden, but little is known about the additional burden of clinical trial (CT) participation. Additionally, CT enrollment among underserved groups is lacking. We sought to examine the impact of a cancer care equity program (CCEP) on CT enrollment and to assess pt-reported barriers to CT participation. Methods: We implemented a CCEP at Massachusetts General Hospital (MGH) in 2014 to help fund non-clinical expenses related to CTs (e.g. travel, lodging). To determine the impact of the CCEP on CT enrollment, we compared CT enrollment in 2014 (after initiating the CCEP) to 2012 and 2013. We used multiple regression analysis to evaluate changes in CT enrollment. To assess financial barriers to CT participation, we administered surveys to CCEP pts and a comparison group of non-CCEP pts. We used chi-square tests to compare CCEP and non-CCEP pts. Results: In 2014, cancer CT enrollment increased by 17% and 40% compared to 2012 and 2013. Adjusting for CT availability, phase, and cancer type, CT enrollment increased significantly from 2013 to 2014 (p = 0.02). In 2014, CT enrollment increased among racial minorities (p < 0.01) and those living > 50 miles from MGH (p < 0.01). Comparing CT pts who enrolled in CCEP to those who did not, more CCEP pts were female (68% vs 51%, p < 0.01), under age 65 (74% vs 64%, p = 0.05), with metastatic disease (90% vs 72%, p < 0.01), incomes < $50k/yr (24% vs 15%, p = 0.03), and in phase I CTs (76% vs 50%, p < 0.01). Of 87 pts who completed the financial barriers survey (61% response rate), we received responses from 49 CCEP pts and 38 non-CCEP pts. More CCEP pts reported financial concerns (56% vs 11%, p < 0.01). Compared to non-CCEP pts, more CCEP pts reported concerns with medical costs (47% vs 14%, p < 0.01), travel (69% vs 11%, p < 0.01), lodging (60% vs 9%, p < 0.01), and insurance coverage (43% vs 14%, p = 0.01) related to CT participation. Conclusions: CT enrollment increased after the implementation of a CCEP, particularly among underserved groups. While CTs often represent the best option for pts with cancer, pts served by the CCEP report significant financial barriers to CT participation. These findings stress the need to recognize and address the financial burden of CT participation.