Dotan E.,Chase Medical |
Meropol N.J.,Case Western Reserve University |
Burtness B.,Chase Medical |
Denlinger C.S.,Chase Medical |
And 7 more authors.
Journal of Gastrointestinal Cancer | Year: 2012
Objectives: Dual inhibition of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) demonstrated initial promise in clinical trials. This phase II study tested the efficacy and safety of capecitabine, oxaliplatin, and cetuximab with or without bevacizumab as first-line treatment for metastatic colorectal cancer patients. Methods: Patients were randomized to receive capecitabine 850 mg/m2 PO twice daily for 14 days, oxaliplatin 130 mg/m2 IV day 1, and cetuximab 400 mg/m2 IV loading dose followed by 250 mg/m2 IV days 1, 8, and 15 with (Arm A) or without (Arm B) bevacizumab 7.5 mg/kg IV day 1 every 21 days. Tumor samples were collected and retrospectively analyzed for KRAS mutation status. The primary endpoint was response rate, with time to progression (TTP) and overall survival (OS) as secondary objectives. Results: Twenty-three patients (12 in Arm A, 11 in Arm B) were enrolled onto the study. Median follow-up was 25.9 months. Both treatments were well tolerated, with expected higher rates of grade 1/2 hypertension and bleeding in Arm A. The overall response rate was 54% (36.4% in Arm A and 72.7% in Arm B). Median time to progression was 8.7 months in Arm A and 14.4 months in Arm B. The median survival was 18.0 months in Arm A and 42.5 months in Arm B. The study was prematurely terminated after other studies reported inferior outcomes with dual antibody therapy. Conclusions: Although terminated early, the study supports the detrimental effect of combining VEGF and EGFR inhibition in metastatic colorectal cancer. © 2012 Springer Science+Business Media, LLC.
Aggarwal C.,University of Pennsylvania |
Meropol N.J.,Case Western Reserve University |
Punt C.J.,University of Amsterdam |
Iannotti N.,Hematology Oncology Associates |
And 8 more authors.
Annals of Oncology | Year: 2013
Background: We previously reported results of a prospective trial evaluating the significance of circulating tumor cells (CTCs) in patients with metastatic colorectal cancer (mCRC). This secondary analysis assessed the relationship of the CTC number with carcinoembryonic antigen (CEA) and overall survival. Patients and methods: Patients with mCRC had CTCs measured at baseline and specific time points after the initiation of new therapy. Patients with a baseline CEA value ≥10 ng/ml and CEA measurements within ±30 days of the CTC collection were included. Results: We included 217 patients with mCRC who had a CEA value of ≥10 ng/ml. Increased baseline CEA was associated with shorter survival (15.8 versus 20.7 months, P = 0.012). Among all patients with a baseline CEA value of ≥25 ng/ml, patients with low baseline CTCs (<3, n = 99) had longer survival than those with high CTCs (≥3, n = 58; 20.8 versus 11.7 months, P = 0.001). CTCs added prognostic information at the 3-5- and 6-12-week time points regardless of CEA. In a multivariate analysis, CTCs at baseline but not CEA independently predicted survival and both CTCs and CEA independently predicted survival at 6-12 weeks. Conclusions: This study demonstrates that both CEA and CTCs contribute prognostic information for patients with mCRC. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Pietanza M.C.,Cornell University |
Gadgeel S.M.,Barbara Ann Karmanos Cancer Institute |
Dowlati A.,Case Western Reserve University |
Lynch T.J.,Harvard University |
And 13 more authors.
Journal of Thoracic Oncology | Year: 2012
XL647 is an oral small-molecule inhibitor of multiple receptor tyrosine kinases, including endothelial growth factor receptor (EGFR), vascular endothelial growth factor receptor 2, HER2 and Ephrin type-B receptor 4 (EphB4). We undertook an open-label, multi-institutional Phase II study to investigate the efficacy and safety of XL647 in treatment-naive non-small-cell lung cancer patients clinically enriched for the presence of EGFR mutations. Methods: Eligibility included patients with advanced-stage treatment-naive lung adenocarcinoma with a known sensitizing mutation of EGFR or patients with at least one of the following criteria: being Asian, female, or having minimal or no smoking history. Two dosing schedules were evaluated; in the "intermittent 5 & 9 dosing" cohort, XL647 350 mg for 5 days every 14 days was given; and in the "daily dosing" cohort, XL647 300 mg daily for 28 days was administered. Tumor EGFR mutation status was determined on available tissue. The primary end point was confirmed objective response rate. Results: Forty-one patients were treated on the intermittent 5 & 9 dosing- and 14 on the daily-dosing schedule. The majority of patients were eligible on the basis of smoking history. The response rate and progression-free survival for the two schedules combined were 20% and 5.3 months (90% confidence interval, 3.7-6.7), respectively. Thirty-eight patients (69%) had material available for mutation testing and 14 EGFR-sensitizing mutations were detected. The response rate and progression-free survival for EGFR-mutation-positive patients were 57% (8/14) and 9.3 months (90% confidence interval, 5.5-11.7). The toxicities were comparable between the two schedules; the most common adverse effects being diarrhea, nausea, and fatigue. Conclusions: XL647 administered on an intermittent or daily-dosing schedule demonstrated antitumor activity in patients with EGFR-activating mutations. The adverse-event profile was similar for the two dosing schedules. Copyright © 2012 by the International Association for the Study of Lung Cancer.
Mok T.S.,Chinese University of Hong Kong |
Geater S.L.,Prince of Songkla University |
Iannotti N.,Hematology Oncology Associates |
Thongprasert S.,Chiang Mai University |
And 10 more authors.
Annals of Oncology | Year: 2014
Background: This phase II, open-label study investigated intercalated combinations of eribulin and erlotinib in unselected patients with advanced non-small-cell lung cancer previously treated with platinum-based chemotherapies. Patients and methods: Eligible patients were randomized to eribulin mesylate 2.0 mg/m2 on day 1 with erlotinib 150 mg on days 2-16 (21-day regimen) or eribulin mesylate 1.4 mg/m2 on days 1 and 8 with erlotinib 150 mg on days 15-28 (28-day regimen). The primary end point was objective response rate (ORR). Results: One hundred and twenty-three patients received ≥1 cycle of therapy (63, 21-day regimen; 60, 28-day regimen). ORRs were 13% [95% confidence interval (CI) 6%-24%] and 17% (95% CI 8%-29%), and disease control rates were 48% (95% CI 35%-61%) and 63% (95% CI 50%-75%) for the 21- and 28-day regimens, respectively. The median progression-free survival and overall survival were similar with both regimens. Both regimens were well tolerated with common grade ≥3 toxicities being neutropenia, asthenia/fatigue, and dyspnoea. Sequential administration of erlotinib did not interfere with the pharmacokinetic profile of eribulin. Conclusion: Intercalated combination of eribulin and erlotinib demonstrated modest activity and the addition of erlotinib did not appear to improve treatment outcome in an unselected population. The 28-day regimen is suitable for further investigation. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Pittock S.J.,Mayo Medical School |
Parisi J.E.,Mayo Medical School |
McKeon A.,Mayo Medical School |
Roemer S.F.,Mayo Medical School |
And 8 more authors.
Archives of Neurology | Year: 2010
Background: Opsoclonus-myoclonus syndrome and breast carcinoma were initially described as neurologic and oncologic accompaniments of antineuronal nuclear autoantibody type 2 (ANNA-2, also known as anti-Ri). However, the neurologic spectrum of ANNA-2 autoimmunity is broader, includes a syndrome of jaw dystonia and laryngospasm, and can be accompanied by lung carcinoma. Objective: To describe clinically (with a video) ANNA-2-associated jaw dystonia and laryngospasm, its pathologic correlates, and therapeutic outcomes. Design: Retrospective case series with prospective clinical follow-up. Setting: Mayo Clinic's Neuroimmunology Laboratory, Rochester, Minnesota. Patients: Consecutive patients with ANNA-2 seropositivity identified since January 1, 1990. Main OutcomeMethods: Clinical (in 9 patients) and neuropathologic (in 2 patients) findings were reviewed. Results: Of 48 patients with ANNA-2 seropositivity, 9 (19%) had multifocal neurologic manifestations that included jaw dystonia and laryngospasm. Among 6 patients with jaw dystonia, 5 had severely impaired nutrition, causing profound weight loss. Five patients had documented laryngospasm, which contributed to 1 patient's death. Neuropathologic examination revealed diffuse infiltration by CD8+ T lymphocytes, with axonal loss and gliosis in brain-stem and descending spinal cord tracts. Some patients improved symptomatically after immunosuppressant or cytotoxic therapies; 1 patient improved after treatment with botulinum toxin. One patient who underwent tracheostomy because of recurrent laryngospasm was alive and well longer than 3 years after symptom onset. Conclusions: Jaw dystonia and laryngospasm are common accompaniments of ANNA-2 autoimmunity and are associated with significant morbidity. We propose that selective damage to antigen-containing inhibitory fibers innervating bulbar motor nuclei by CD8 + T lymphocytes (histopathologically observed infiltrating brain-stem reticular formation) is the proximal cause of this syndrome. Early and aggressive therapy offers the prospect of neurologic improvement or stabilization. ©2010 American Medical Association. All rights reserved.
Dewar R.,Beth Israel Deaconess Medical Center |
Chen S.-T.,Clarient |
Yeckes-Rodin H.,Hematology Oncology Associates |
Miller K.,Tufts Medical Center |
And 2 more authors.
Cancer Biology and Therapy | Year: 2011
BCR-ABL is a key mediator in the pathogenesis of all cases of chronic myelogenous leukemia (CML) and a subset of precursor B-acute lymphoblastic leukemia (Ph+ALL). Previous animal and cell-based studies have shown that the expression of members of the Forkhead family of tumor suppressors, including FoxO3, is suppressed in BCR-ABL-expressing cells. Furthermore, it has been reported that the proteasomal degradation pathway plays an important role in suppression of FoxO expression in BCR-ABL-transformed cells. In this study, a patient diagnosed with Ph+ALL and refractory to standard therapies was treated with a proteasome inhibitor (bortezomib)-based chemotherapy regimen. This treatment resulted in complete hematologic, cytogenetic and molecular remission with excellent performance status for >4 years since her initial diagnosis. FoxO3 was not detectable within the blasts of this patient at diagnosis and was 'rescued' following treatment with bortezomib therapy, leading to her recovery. As a next step, in the attempt to propose FoXO3 as a therapeutic target and a theranostic marker, we further validated FoxO3 expression in human bone marrow biopsy samples. Human core biopsy samples of Ph+ALL and Ph-negative-negative ALL, along with uninvolved controls, revealed that FoxO3 downregulation was specific to Ph+ALL. This study provides support that FoxO3 is a good biomarker for BCR-ABL-mediated leukemogenesis. Additionally, proteasomal inhibition by bortezomib may be a promising therapeutic option in Philadelphia-positive ALL, where FoxO3 is downregulated. © 2011 Landes Bioscience.
Winkeljohn D.,Hematology Oncology Associates
Clinical Journal of Oncology Nursing | Year: 2013
Management of immune thrombocytopenia (ITP) requires accurate assessment and evaluation, appropriate treatment strategies, and timely nursing interventions (e.g., monitoring, bleeding prevention, patient education). The overview of ITP in the current article reviews its etiology and provides updates about medical management and key components of nursing care. © Oncology Nursing Society.
Duncan B.P.R.,Hematology Oncology Associates |
Lin J.T.,Hematology Oncology Associates
Journal of Oncology Practice | Year: 2011
Purpose: Genetic cancer risk assessment (GCRA) has become increasingly important in clinical cancer care. Almost all published information on genetic risk assessment has come from academic institutions. However, a majority of patients with cancer are seen in the community practice setting. Methods: We describe the evolution of a community oncology practice GCRA clinic. Results: Over a 10-year period, 445 patients were seen for a possible genetic cancer syndrome. This included 325 patients with family history of breast or ovarian cancer, 92 patients with family history of colorectal cancer or polyposis, and 28 families with another familial cancer predisposition. Fifty-three unique families with a genetic mutation were identified. Conclusion: A GCRA clinic can be incorporated into an oncology practice setting and can enhance the standard of care for the entire community. We present data reflecting a 10-year experience with such a clinic and provide recommendations for establishing a successful one. Copyright © 2011 by American Society of Clinical Oncology.
Winkeljohn D.,Hematology Oncology Associates
Clinical Journal of Oncology Nursing | Year: 2010
This article reviews nursing interventions to increase adherence to oral cancer therapies, such as patient and care-partner education, side-effect and medication management, and safety issues. Data sources included peer-reviewed nursing and medical literature, healthcare Web sites, and published monographs. Oncology nurses are uniquely positioned to promote patient adherence to oral cancer therapies by ensuring that patients understand the goals of treatment, promoting safe prescriptive practices, proactively managing treatment side effects, and identifying and resolving underlying barriers to adherence. When adherence is optimized, clinical outcomes are greatly improved. Primary responsibility for adherence to an oral cancer therapy regimen remains with the patient. Oncology nurses, as part of a healthcare team, can have a significant influence on patient adherence by providing thorough and timely patient and family education and by monitoring and managing side effects of treatment. Monitoring adherence to oral cancer therapies is not a recent phenomenon nor limited to oral cancer treatments but presents an increasing challenge as additional oral therapies enter the marketplace. Oncology nurses should develop and enhance strategies and materials for patient education on oral cancer therapies, improve side-effect management, assist with patient access to medications, and develop practice guidelines to ensure adherence and promote safety.
PubMed | Hematology Oncology Associates
Type: Journal Article | Journal: Clinical journal of oncology nursing | Year: 2013
Management of immune thrombocytopenia (ITP) requires accurate assessment and evaluation, appropriate treatment strategies, and timely nursing interventions (e.g., monitoring, bleeding prevention, patient education). The overview of ITP in the current article reviews its etiology and provides updates about medical management and key components of nursing care.