West End, TN, United States
West End, TN, United States

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Hainsworth J.D.,Sarah Cannon Research Institute SCRI | Hainsworth J.D.,Tennessee Oncology PLLC | Greco F.A.,Sarah Cannon Research Institute SCRI | Greco F.A.,Tennessee Oncology PLLC | And 7 more authors.
Clinical Lymphoma, Myeloma and Leukemia | Year: 2014

Introduction/Background Inhibition of tumor angiogenesis by the interruption of VEGF pathway signaling is of therapeutic value in several solid tumors. Preclinical evidence supports similar importance of the pathway in non-Hodgkin lymphoma. In this randomized phase II trial, we compared the efficacy and toxicity of rituximab with bevacizumab versus single-agent rituximab, in patients with previously-treated follicular lymphoma. Patients and Methods Patients (n = 60) were randomized (1:1) to receive rituximab (375 mg/m2 intravenously [I.V.] weekly for 4 weeks) either as a single agent or with bevacizumab (10 mg/kg I.V. on days 3 and 15). Patients with an objective response or stable disease at week 12 received 4 additional doses of rituximab (at months 3, 5, 7, and 9); patients who received rituximab/ bevacizumab also received bevacizumab 10 mg/kg I.V. every 2 weeks for 16 doses. Results After a median follow-up of 34 months, PFS was improved in patients who received rituximab/bevacizumab compared with patients who received rituximab alone (median 20.7 vs. 10.4 months respectively; HR, 0.40 (95% confidence interval [CI], 0.20-0.80); P =.007). Overall survival was also improved numerically (73% vs. 53% at 4 years), but did not reach statistical significance (HR, 0.40 (95% CI, 0.15-1.05); P =.055). The addition of bevacizumab increased the toxicity of therapy, but both regimens were well tolerated (no grade 4 toxicity). Conclusion The addition of bevacizumab to rituximab significantly improved PFS. The role of angiogenesis inhibition in the treatment of follicular lymphoma requires further definition in larger clinical trials. © 2014 Elsevier Inc. All rights reserved.

Bendell J.C.,Sarah Cannon Research Institute SCRI | Bendell J.C.,Tennessee Oncology PLLC | Meluch A.,Tennessee Oncology | Peyton J.,Tennessee Oncology | And 4 more authors.
Clinical Advances in Hematology and Oncology | Year: 2012

Purpose: To evaluate the efficacy of bevacizumab (Avastin, Genentech) and erlotinib (Tarceva, Genentech/Roche) when added to preoperative chemoradiation therapy with paclitaxel, carboplatin, and infusional 5-fluorouracil (5-FU) in the treatment of localized cancers of the esophagus or gastroesophageal (GE) junction. The primary endpoint was the pathologic complete response (pCR) rate. Methods: Eligible patients had previously untreated localized squamous cell, adenocarcinoma, or adenosquamous carcinoma of the esophagus or GE junction, and were considered surgical candidates at enrollment. Daily erlotinib (100 mg orally) was administered on days 1-42 of preoperative treatment. Patients received paclitaxel (200 mg/m2 intravenously [IV]), carboplatin (area under the curve [AUC] 5.0 IV), and bevacizumab (15 mg/kg IV) on days 1 and 22, and 5-FU by continuous infusion (225 mg/m2/day IV) on days 1-35, with radiation therapy in 1.8-Gy single fractions, Monday-Friday (to a total of 45 Gy). Those who were deemed surgical candidates proceeded to resection during weeks 12-14. Results: Between February 2007 and September 2009, 62 patients (median age, 64 years; 92% male; 94% adenocarcinoma) were enrolled; 44 patients (71%) completed neoadjuvant treatment and proceeded to surgery. Eighteen patients (29%) achieved pCR, with partial pathologic remission in an additional 22 patients (35%). Common grade 3/4 toxicities included leukopenia (64%), neutropenia (44%), mucositis/stomatitis (42%), diarrhea (27%), and esophagitis (27%). There were 40 instances of treatment-related hospitalization, and 2 postoperative deaths. Conclusions: The addition of bevacizumab and erlotinib to neoadjuvant chemoradiation did not demonstrate survival benefit or improved pCR rate over similar regimens. While the overall rates of toxicity were not increased, targeted agent-specific toxicity was evident. Further study of this specific regimen is not warranted.

Varadhachary G.R.,University of Houston | Karanth S.,University of Houston | Qiao W.,University of Houston | Carlson H.R.,University of Houston | And 5 more authors.
International Journal of Clinical Oncology | Year: 2014

Background: Carcinoma of unknown primary with a "gastrointestinal profile" is an emerging, favorable entity. Distinguishing this entity is of increasing significance given the progress in the treatment of colorectal cancer. Patients and methods: 74 carcinoma of unknown primary (CUP) patients with CDX2+ tumors were chosen from the databases at M.D. Anderson and Sarah Cannon Cancer Centers between 2004 and 2010. Data on clinical and pathological characteristics including therapy and survival were recorded. Results: 20 patients had ascites on presentation; the predominant sites of metastases included liver (30 %), carcinomatosis (50 %), and nodes (51 %). Based on immunohistochemistry, 2 cohorts were created: Cohort 1-"consistent with lower GI profile" included 34 patients [CDX-2+, CK20+, CK7-] and Cohort 2-"probable lower GI profile" included 40 patients [CDX2+, irrespective of CK7/CK20 status]. Excluding 6 outliers, Cohorts 1 and 2 had 32 and 36 patients, respectively; their median survivals were 37 and 21 months, respectively. On multivariate Cox regression analysis, only liver metastases were found to negatively influence survival. Conclusions: Our retrospective study provides encouraging indications that CUP patients with gastrointestinal profiles benefit from site-specific therapy. We recommend all CUP patients, especially those with abdominal nodes, isolated carcinomatosis or liver metastases, to undergo optimal immunohistochemistry (IHC) to check for a gastrointestinal profile of CUP. © 2013 Japan Society of Clinical Oncology.

Tall fescue (Festuca arundinacea) forms a mutualistic symbiosis with the fungal endophyte Neotyphodium coenophialum which produces ergot alkaloids toxic to grazing animals. One approach to reduce pathological effects has been to introduce an exotic endophyte that does not produce toxic compounds yet still confers host-plant benefits. We measured biomass accumulation and competition between two tall fescue cultivars with different endophytes grown in close proximity and tested if compounds from endophytes can diffuse from one plant to another. Ky31 (tall fescue with natural endophyte) and MaxQ (tall fescue with introduced exotic endophyte) were grown separately and together in a pot experiment under greenhouse conditions. The cultivars had comparable biomass production in monoculture, but when grown in mixed-culture MaxQ had a significantly lower tiller number (2.92 ± 0.15 tillers/plant) and size (0.048 g ± 0.003) than Ky31 (4.06 ± 0.16 tillers/plant) (0.072 ± 0.002 g). Aqueous endophyte preparations were made and applied topically to E+ and E- Ky31. E- plants receiving doses of this preparation produced significantly more tillers (3 ± 0.18 tillers/plant) and larger tillers (0.074 ± 0.006 g) than untreated control plants (2.2 ± 0.13 tillers/plant) (0.0428 ± 0.0072 g). These observations suggested that a diffusible compound might induce a growth benefit conferred by the tall fescue endophyte. © 2012 Blackwell Publishing Ltd.

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