tbuckley/cabot-search huggingface dataset:
NSABP B-43: A phase III clinical trial to compare trastuzumab (T) given concurrently with radiation therapy (RT) to RT alone for women with HER2+ DCIS resected by lumpectomy (Lx).
Authors: Melody A. Cobleigh, Stewart J. Anderson, Thomas B. Julian, Kalliopi P. Siziopikou, Douglas W. Arthur, Rachel Rabinovitch, Ping Zheng, Eleftherios P. Mamounas, Norman Wolmark
Journal: Journal of Clinical Oncology (2013)

TPS666 Background: A significant amount of DCIS is ER-negative and/or overexpresses HER2. This study will test HER2-targeted therapy in DCIS. Among T-treated HER2+ patients (pts) with DCIS treated with a single dose of T, T is found in ductal aspirates and antibody-dependent cell-mediated cytotoxicity activity for HER2 is increased. T boosts the effectiveness of RT in breast cancer xenograft models and cell lines. T given during whole breast irradiation (WBI) may improve results for HER2+ DCIS treated with lumpectomy (Lx). A trial to examine this question will enhance the understanding of breast tumor biology, the prevention of such tumors, and could possibly extend breast-conserving surgery benefits for women with DCIS. Methods: After Lx for pure DCIS, each pt’s DCIS lesion is centrally tested for HER2 using ASCO/CAP guidelines. HER2+ pts are randomly assigned to receive 2 doses of T, 3 weeks apart during WBI or to WBI alone. Women ≥18 yrs with a margin-clear Lx for pure DCIS, with ECOG status 0/1 who are clinically or pathologically node negative are eligible. ER and/or PR status must be known before random assignment. Primary aims are to determine if T decreases ipsilateral breast cancer (IBC) recurrence, ipsilateral skin cancer recurrence, or ipsilateral DCIS. Secondary aims are to determine the benefit of T in preventing regional or distant recurrence and contralateral invasive breast cancer or DCIS. B-43 will determine if DFS, recurrence-free interval, and/or overall survival can be improved with the use of T. 2000 pts will be accrued over 7.9 yrs, with a definitive analysis of primary endpoints performed at163 IBC events (7.5 - 8 yrs after protocol initiation) with an 80% power to detect a hazard reduction of 36%, from 1.73 IBC events per 100 pt-yrs to 1.11 events per 100 pt-yrs. The 36% observed reduction in the hazard of IIBCR-SCR-DCIS on the T arm is based on a projection of 40% hazard reduction if the compliance were perfect, with a 10% noncompliance rate. As of 1-1-13, 1,127 pts have been randomized into the study. Support: PHS NCI-U10-CA-69651, -12027, and -P30-CA-14599 from the US NCI, and Genentech, Inc. Clinical trial information: NCT00769379.
Correlations of molecular alterations in clinical stage III cutaneous melanoma with clinical-pathological features and patients outcome.
Authors: Piotr Rutkowski, Monika Jurkowska, Aleksandra Gos, Andrzej Tysarowski, Wanda Michej, Tomasz Switaj, Wirginiusz Dziewirski, Marcin Zdzienicki, Slawomir Falkowski, Wlodzimierz Tadeusz Olszewski, Janusz A Siedlecki
Journal: Journal of Clinical Oncology (2012)

8548 Background: To evaluate frequency and type of oncogenic BRAF/NRAS mutations in cutaneous melanoma with clinically detected nodal metastases (stage IIIB,C) in relation to clinicopathologic features and outcome. Methods: We analyzed 221 patients after therapeutic lymphadenectomy-LND (1995-2010) not treated with tyrosine kinase inhibitors and performed molecular characterization of nodal metastases in terms of BRAF/NRAS genes (analyzed by sequencing of respective coding sequences). Median follow-up time was 53 months. Results: BRAF mutations were detected in 139 (63%) cases (127–V600E, 8–V600K, 4-others), mutually exclusive NRAS mutations in 35(15.8%) cases (mainly Q61R and Q61K). BRAF mutation presence correlated with patients' younger age(median 52 vs 60 years for BRAF+ vs. BRAF-, p&lt;0.05), metastases in axillary basin (p&lt;0.05) and less involved nodes (median 3 vs. 4; p&lt;0.05). 5-year overall survival (OS) was 35% and 45% (calculated from date of LND and primary tumor excision, respectively); 5-year recurrence-free survival RFS (from LND) – 29%. We have not found correlation between mutational status and RFS or OS (calculated from date of LND and primary tumor excision) – for BRAF mutated-melanomas prognosis was the same as wild-type melanoma patients(p=0.26) with even trend for better OS for non-V600E mutants. Negative prognostic factors (in univariate and multivariate analysis) for OS and RFS were: male gender (p&lt;0.01), metastatic lymph nodes&gt;1 (p&lt;0.001), nodal metastases extracapsular extension (p&lt;0.001). The interval from diagnosis of first-ever melanoma to regional nodal metastasis (median-10 months) was not significantly different between BRAF-mutant and BRAF wild-type patients (p=0.29). Conclusions: BRAF/NRAS mutational status is not prognostic marker in stage III melanoma patients with macroscopic nodal involvement, what may have implication for potential adjuvant therapy. BRAF status had no impact on disease-free interval from diagnosis of primary melanoma to nodal metastases. Our first-ever comprehensive molecular analysis of clinical stage III melanomas revealed that BRAF-mutants show characteristic clinicopathologic features.
Oral talactoferrin extends survival in patients with refractory NSCLC in a randomized, placebo-controlled, phase 2 trial
Authors: P. K. Parikh, Y. Wang, A. A. Ranade, A. K. Vaid, S. H. Advani, D. Raghunadharao, S. Nag, J. P. Madhavan, A. Varadhachary
Journal: Journal of Clinical Oncology (2007)

7540 Background: Talactoferrin alfa (TLF), an immunomodulatory protein with a novel anti-cancer mechanism of action, was active preclinically and in non-small cell lung cancer (NSCLC) patients in Phase 1b studies. Randomized Phase 2 studies in NSCLC were conducted with TLF as a single agent and combined with chemotherapy. The 110-patient combination therapy study, which was previously presented (ASCO 2006, #7095), met its primary endpoint with an improved BOR over chemotherapy alone. We now present results from the placebo- controlled single agent study. Methods: 100 Stage IIIB/IV NSCLC patients who had progressed after first or second line therapy were enrolled at 10 leading Indian cancer centers, and randomized to receive best supportive care plus either oral TLF (1.5 g bid) or placebo. TLF/placebo was administered until disease progression, for up to three 14-week cycles (12 weeks on, 2 weeks off), in a centrally monitored trial. The primary endpoint was overall survival (OS) with 80% power to detect an improvement in median OS with an a=0.05. Results: All patients had previously received a 1 st line platinum based regimen; 26 also received 2nd line therapy. The TLF and placebo arms enrolled 47 and 53 patients, respectively. Baseline characteristics were similar in both groups, including proportion of patients receiving 1 or 2 prior regimens. All patients were included in the Intent To Treat (ITT) analysis. The trial met its primary endpoint with a 55% increase (2.1 month; p&lt;0.05) in median OS. TLF was well tolerated. Adverse Events (AEs) were generally mild. No drug- related SAEs were reported. Incidence of AEs and Grade 3/4 AEs was similar in both arms. Conclusion: Oral talactoferrin, a promising new anti-cancer agent, significantly improved survival in patients with refractory NSCLC in this randomized, placebo-controlled trial. TLF was well tolerated in this population. Given its favorable toxicity profile, TLF may be particularly attractive in refractory patients with poor performance status. [Table: see text] [Table: see text]
A randomized double-blind phase II trial of platinum (P) plus etoposide (E) with or without concurrent ZD6474 (Z) in patients (pts) with previously untreated extensive-stage (ES) small cell lung cancer (SCLC): Hoosier Oncology Group LUN06-113.
Authors: Rachel E. Sanborn, Jyoti D. Patel, Gregory A. Masters, Nagesh Jayaram, Anthony W. Stephens, Michael J. Guarino, Jamal Ghazi Misleh, Corinne E. Williams, Jingwei Wu, Nasser H. Hanna
Journal: Journal of Clinical Oncology (2014)

7506 Background: Standard treatment with P + E results in median survival for ES SCLC 10 months. Dose escalation, addition of third cytotoxic agents, and maintenance therapy have failed to improve outcomes. Overexpression of VEGF is associated with poor prognosis in SCLC. This trial evaluated the efficacy and tolerability with the addition of Z (dual VEGF and EGFR inhibitor) to PE. Methods: Randomized, double blind, placebo controlled study of P (cisplatin 60 mg/m2 or carboplatin AUC 5) day 1, E (120 mg/m2 with cis or 100 mg/m2with carbo) IV days 1-3, with Z (100 mg) or placebo po daily, q3 wks for 4 cycles. 6 pts were initially enrolled on P+E+Z for safety assessment. Pts with untreated ES SCLC or high grade poorly differentiated neuroendocrine tumors and ECOG 0-1 were eligible. Pts with symptomatic brain metastases (mets) or prolonged QTc were ineligible. 1°endpoint was time to disease progression (TTP). Secondary endpoints were safety, response rate (RR), disease control rate (DCR), and overall survival (OS). VEGF polymorphisms were also evaluated. Results: 74 pts enrolled (33 placebo, arm A; 41 Z, arm B) Median age 63/64 A/B; female/male 48.5%/51.5% A, 41.5%/58.5% B; ECOG 0/1 36%/64% A, 34%/66% B. Brain mets at diagnosis, 30% A, 39% B. Median number of cycles received was 4 (both arms). Cisplatin/carboplatin 51.5%/48.5% A, 61%/39% B. All Grade (Gr) 3-4 toxicity: 37% A, 69% B (heme, 20% A; 30% B, mainly neutropenia both arms; non-heme, 17% A; 33% B). Gr 5 toxicity, 1 each: A, 3 (cardiac infarct, pulmonary hemorrhage, pneumonitis); B, 2 (infection, respiratory failure). No differences were seen in bleeding/hemorrhage (1 gr 3/4 each, 1 gr 5 A). 3 pts had Gr 3/4 hypertension in B (0 in A). RR 65.4% A, 51.4% B; P=0.31. DCR 73% A, 74% B; P=1.0. Median OS 10.2 months (mo) A, 10.7 mo B; P=0.90; HR 0.78 (B v A). Median TTP 5.6 mo A, 5.5 mo B; P=0.66; HR 1.13 (B v A). Conclusions: The addition of Z to PE did not improve TTP, RR, DCR, or OS for patients with extensive SCLC. An increase in toxicity was seen with Z compared with placebo. Z in combination with PE cannot be recommended for further study in unselected pts with ES SCLC. Clinical trial information: NCT00613626.
Giant duodenal hematoma after duodenal biopsy in a patient with suspected acute gastrointestinal graft-versus-host disease
Authors: Robert Henker, Sebastian Schwind, Christine Döhring, Mario Heindl, Maximilian Beimler, Albrecht Hoffmeister, Thomas Karlas
Journal: Endoscopy (2017)

A 21-year-old man developed nausea and weight loss 2 months after undergoing allogenic hematopoietic stem cell transplantation for treatment of acute myeloid leukemia. He was referred to gastrointestinal endoscopy for a duodenal biopsy, which is a procedure commonly used to confirm the diagnosis of acute graft-versus-host disease (GvHD) [1]. His coagulation test results were within the normal ranges and his platelet count was 52 × 109/L. The examination was uneventful and a duodenal biopsy was performed without significant bleeding ([Fig. 1]).
Is neoadjuvant chemotherapy beneficial before radical cystectomy? Examining the external validity of the SWOG-8710 trial.
Authors: Nawar Hanna, Quoc-Dien Trinh, Jesse Sammon, Thomas Seisen, Malte Vetterlein, Raphael Brandao Moreira, Mark A Preston, Stuart R. Lipsitz, Joaquim Bellmunt, Mani Menon, Toni K. Choueiri, Firas Abdollah
Journal: Journal of Clinical Oncology (2017)

331 Background: The use of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) is supported by results from several randomized control trials, including SWOG-8710. We sought to test the applicability of the SWOG-8710 study in the general population. Methods: We used the National Cancer Data Base (NCDB) to identify patients with non-metastatic muscle-invasive urothelial carcinoma of the bladder who underwent RC between 2004 and 2012. The primary endpoint was overall survival (OS). Secondary endpoints were rates of downstaging (pT0), positive pathologic lymph nodes (pN+), margin status, postoperative readmission, length of hospital stay (LOS), and 30 and 90-day postoperative mortality rates. OS comparison using Cox regression analysis was conducted. Furthermore, logistic regression models examining secondary outcomes were fitted. To adjust for potential selection bias, propensity score weighted analyses were performed. Results: Of 8732 patients who underwent RC, 1619 (19%) received NAC. Compared to the SWOG-8710 cohort, our population was older, more commonly female (p=0.002), and had higher clinical stage (p&lt;0.001). Following propensity score adjustment, receipt of NAC was associated with an OS benefit (Hazard Ratio [HR]: 0.88, p=0.017). On secondary outcome analysis, higher downstaging rates (Odds Ratio [OR]: 5.03, p&lt;0.001) and lower 30-day (OR: 0.49, p=0.019) and 90-day (OR: 0.61, p=0.009) postoperative mortality rates were recorded in patients who received NAC. Conclusions: Despite baseline differences between patients from the SWOG-8710 trial and general urologic practice, NAC is associated with an OS advantage relative to RC alone. Continued efforts should focus on promoting the use of NAC in appropriate patients.
A phase I/II study of oral paclitaxel in patients (pts) with advanced gastric cancer.
Authors: Kyung Hee Lee, Young-Iee Park, Dae Young Zang, Keun-Wook Lee, Dongbok Shin, Kyung-Mi Park, Jeewoong Son, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2012)

e14572 Background: Paclitaxel is not absorbed from GI tract because of the over- expression of P-glycoprotein by intestinal cells. In previous study, Oraxol, which composed of paclitaxel solution and HM30181A tablet, a novel P-glycoprotein inhibitor, had been administered to 25 pts with advanced solid cancer. Thereafter, the formulation of Oraxol was changed from paclitaxel slolution to paclitaxel capsule. Methods: Primary objective for Phase I study was to determine the maximum tolerable dose (MTD) or recommended dose (RD) of Oraxol using standard 3+3 dose escalation design at three pre-specified doses (180, 240, 300 mg/m 2 /week of paclitaxel capsule, fixed dose of 15 mg/day HM30181AK tablet). Oraxol was administrated twice a week, total 6 times per cycle (day 1, 2, 8, 9, 15 and 16), every 4 weeks.Eligible ptswere ≥ 19 years with advanced malignancies refractory to standard therapies in Phase I portion. Primary objective for phase II study was to evaluate the clinical response of pts with advanced or metastatic/recurrent gastric cancer after failure of 1 previous chemotherapy. In the phase II study, patients were enrolled in 2 stages Results: In pase I study, 10 pts were enrolled and 4 had treatment-related AEs. One pt had treatment-related grade 3 anemia, 2 pts had treatment-related grade 2 AEs: neutropenia, thrombocytopenia and asthenia. No DLT was observed in the dose range of this study and the RD for phase II was defined at 300 mg/m 2 /week (150 mg/m 2 x 2) based on the safety profiles and plasma concentration profiles. The phase II study is ongoing. Thirty patients have been enrolled to date. Of 25 pts evaluable for efficacy, 1 had complete response (not confirmed) after 8 weeks of therapy, 3 subjects had partial response (duration of treatment: 8.83 mo+, 3.07 mo+, 3.03 mo+), and 10 had stable disease (SD) as best response. Conclusions: Oraxol has been well tolerated and has shown promising efficacy in gastric cancer patients. Updated results will be presented at the meeting.
Phase II multicenter trial of docetaxel+oxaliplatin in stage IV gastroesophageal and/or stomach cancer
Authors: D. A. Richards, L. Wilfong, D. Reznick, D. McCollum, K. A. Boehm, F. Zhan, L. Asmar
Journal: Journal of Clinical Oncology (2006)

4071 Background: The treatment of adenocarcinoma of the gastroesophageal junction /stomach (AGEJ/S) remains a therapeutic challenge. This study was conducted to explore the efficacy and safety profile of the combination of docetaxel+oxaliplatin in patients with previously untreated advanced AGEJ/S. Docetaxel has shown significant single-agent activity and has recently been shown to increase response rates and overall survival when combined with cisplatin plus 5-FU. Oxaliplatin is associated with a more favorable safety profile compared to other platinum-based drugs (ie, cisplatin). Methods: Patients with metastatic (Stage IV) AGEJ/S were eligible. Treatment consisted of docetaxel 60 mg/m 2 over 1 hour IV followed by oxaliplatin 130 mg/m 2 over 2 hours on Day 1 of each 21-day cycle. Patients were treated until disease progression or unacceptable toxicity; primary endpoints are response rate, toxicity, and progression free and overall survival. Results: We have enrolled all planned eligible patients (N = 71). Baseline characteristics include a median age of 59.5 years, 72% male patients, 76% white, and ECOG PS scores 0/1/2 of 45%/49%/6%, respectively. 32.8% of patients had distal gastric cancer (fundus or pylorus). The median number of cycles delivered to date is 6 (range, 1–14). Twenty patients (31%) have required dose reductions primarily due to neutropenia. Grade 3–4 toxicities include neutropenia (69%); vomiting (17%); nausea (16%); dehydration, fatigue, and diarrhea (13%, each), and thrombocytopenia and febrile neutropenia (7%, each). Sixty-six patients have completed ≥2 cycles. The best overall confirmed response rate, by RECIST, was 24 PR (35.6%) for an overall response rate of 35.6%. Median time to response was 2.4 months and median duration of response was 4.1 months. Median survival was 9.2 months and median PFS was 4.4 months. Conclusions: The combination of docetaxel and oxaliplatin is associated with manageable toxicity in this group of patients with AGEJ/S. The best overall response rate of 35% and median survival of 9.2 months is encouraging and comparable to other standard front-line regimens. This research was supported, in part, from a research grant from sanofi-aventis. [Table: see text]
A phase II trial of gefitinib monotherapy in pretreated patients with advanced non-small cell lung cancer not harboring activating EGFR mutations.
Authors: Moon Ki Choi, Jung Yong Hong, Won Jin Chang, Moonjin Kim, Sungmin Kim, Hyun Ae Jung, Sung Hee Lim, Ji Yun Lee, Ingu Do, Yoon-La Choi, Jong-Mu Sun, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Journal: Journal of Clinical Oncology (2014)

e19155 Background: Efficacy of gefitinib therapy strongly depends on epidermal growth factor receptor (EGFR)-mutation status in patients with non-small cell lung cancer (NSCLC). However, cumulative data from many clinical studies demonstrated that some patients with wild-type (WT) EGFR also responded to gefitinib and remained stable. The aim of this trial was to evaluate the efficacy and toxicity of gefitiinb in NSCLC patients who failed previous chemotherapy with WT EGFR tumors. Methods: Patients with advanced or recurrent NSCLC whose tumors have WT EGFR were eligible. Gefitinib (250 mg/day) was administered until disease progression or unacceptable toxicity occurred. The primary end point was disease control rate (DCR) at 8 weeks. Results: Eighty-five patients (53 men and 32 women; median age, 60 years; range, 30-86) were enrolled between October 2010 and May 2013. Seventy-four (87.1%) had adenocarcinoma, nine (10.6%) had squamous cell carcinoma. Forty-one patients (48.2%) were treated with gefitinib as second-line chemotherapy and 34 patients (40.0%) as third-line chemotherapy. Eleven patients showed partial response, and twenty-one had stable disease. Thus, response rate was 12.9%, and DCR was 37.6%. Skin rash was the most common side effect. One patient developed interstitial lung disease (grade 2). The median progression-free survival and overall survival times were 1.9 and 10.9 months, respectively. Conclusions: Gefitinib might be an alternative option for pretreated patients even in those with WT EGFR NSCLC.
A phase I study of EMD 525797, a novel humanized monoclonal antibody to human integrin alpha v, in Japanese patients with solid tumor.
Authors: Toshihiko Doi, Nozomu Fuse, Hideaki Bando, Takashi Kojima, Morihiro Watanabe, Takayuki Yoshino, Atsushi Ohtsu
Journal: Journal of Clinical Oncology (2013)

e13510 Background: Integrin alpha v, in association with several integrin beta subunits, plays critical roles in migration, invasion, proliferation, and survival of both tumor and endothelial cells and represents an attractive target for cancer treatment. EMD 525797 is a humanized monoclonal IgG2 antibody specifically targeting integrin alpha v. Methods: The safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of EMD 525797 were assessed in Japanese patients with advanced solid tumors, treated with intravenous infusions of 250, 500, 1000, or 1500 mg of EMD 525797 (given over 1 h), who received 3 doses (weeks 1, 3, and 5) before response assessment during week 6. Thereafter, patients without progressive disease could receive further doses every 2 weeks. Dose-limiting toxicities (DLTs) were assessed over the first 4 weeks and safety was monitored until 31 days after the last administration of EMD 525797. Results: A total of 27 patients were treated. Regarding the primary site of disease, 17 patients had colorectal cancer, 3 pancreatic cancer, 2 gastrointestinal stromal tumors (GIST), 1 esophageal cancer, 1 gastric cancer, 1 rectal carcinoid, 1 cholangiocarcinoma, 1 hepatocellular carcinoma, and 1 leiomyosarcoma. Twenty-five patients (92.6%) experienced treatment-emergent adverse events (TEAEs); nausea (25.9%), headache (22.2%), pyrexia (22.2%), stomatitis (22.2%), and vomiting (22.2%) were the most common. None of these TEAEs was greater than grade 3 by NCI-CTCAE version 4.0 and no DLT was observed. Fourteen (51.9%) of the TEAEs were possibly related to EMD 525797. Two patients, 1 with GIST and 1 with rectal carcinoid, had longer than expected exposure time (&gt;84 days). EMD 525797 showed a non-linear PK profile. Distribution volume and clearance after EMD 525797 administration did not show apparent ethnic difference considering body weight influence. Conclusions: EMD 525797 was well tolerated in Japanese patients. The safety profile in Japanese patients was comparable to the results from Caucasian patients. In some patients EMD 525797 treatment duration was longer than expected. Clinical trial information: NCT01327313.