PubMed | National Cancer Center Hospital, Oncology Institute of Southern Switzerland, Sloan Kettering Cancer Center, University of Bologna and 10 more.
Type: | Journal: Nature reviews. Clinical oncology | Year: 2016
The landscape of drugs for the treatment of lymphoma has become crowded in light of the plethora of new agents, necessitating the efficient prioritization of drugs for expedited development. The number of drugs available, and the fact that many can be given for an extended period of time, has resulted in the emergence of new challenges; these include determining the optimal duration of therapy, and the need to balance costs, benefits, and the risk of late-onset toxicities. Moreover, with the increase in the number of available investigational drugs, the number of possible combinations is becoming overwhelming, which necessitates prioritization plans for the selective development of novel combination regimens. In this Review, we describe the most-promising agents in clinical development for the treatment of lymphoma, and provide expert opinion on new strategies that might enable more streamlined drug development. We also address new approaches for patient selection and for incorporating new end points into clinical trials.
Wang J.,87680 Nebraska Medical Center |
Wang J.,Arizona Cancer Center |
McGuire T.R.,86045 Nebraska Medical Center |
Britton H.C.,86495 Nebraska Medical Center |
And 4 more authors.
Clinical and Experimental Metastasis | Year: 2015
Lenalidomide (LEN) and metronomic cyclophosphamide (CTX) regulate angiogenesis and immunosuppressive cells linked to the progression of metastatic castration-resistant prostate cancer (mCRPC). A phase-I/II, dose-escalation trial of LEN plus oral CTX was conducted in patients with previously treated mCRPC. In the phase-I study, CTX was given at 50 mg (day 1–28) and LEN at 10–25 mg (day 1–21) on a 28-day cycle using a “3+3” study design. In phase II, patients received LEN at 25 mg (day 1–21) with CTX at 50 mg PO QD (day 1–28) on a 28-day cycle. Nineteen patients in phase I were evaluable for toxicity. The maximum tolerated dose (MTD) was not observed at any of the dose levels (DLs) tested. Six patients received treatment in phase II before the trial was closed. A ≥ 50 % reduction in PSA was observed in 31.7 % evaluable patients. Radiographically, one patient had a partial response. Stable disease was documented in 68 % of evaluable patients after two therapy cycles. Circulating tumor cells (CTCs) decreased in 22.7 % and remained stable in 31.8 % of patients. Baseline numbers of peripheral MDSCs (MDSC; Lin-DR−CD11b+) were significantly increased in patients versus normal donors, and were decreased by chemotherapy. At baseline, MDSCs correlated directly with CTCs, and inversely with T- and B cell frequency supporting their immunosuppressive activity. The combination of LEN and metronomic CTX can be safely administered, reversing cellular immunosuppression in this group of elderly patients with mCRPC. Further research is required to identify responsive subgroup(s) and validate the biomarkers. © 2015, Springer Science+Business Media Dordrecht.
Bhatt V.R.,87680 Nebraska Medical Center |
Shrestha R.,Memorial Hospital of Rhode Island |
Krishnamurthy J.,University of Nebraska Medical Center |
Mosalpuria K.,University of Nebraska Medical Center |
And 3 more authors.
Therapeutic Advances in Medical Oncology | Year: 2015
Background: The incidence of melanoma in older patients is on the rise. Prior studies have shown disparities in surgical management and poor survival of older patients with melanoma. Methods: This is a retrospective study of adult patients diagnosed with cutaneous invasive and in situ melanoma between 2000 and 2011 in the National Cancer Data Base. Characteristics and management of older patients (≥60 years) were compared with younger patients (20-59 years) using χ2 testing. Results: Of 476,623 total cases, 54% (n = 258,153) were diagnosed among older patients. The reported cases in the older patients increased by 1.74-fold between 2000 and 2011. The majority were white (96%), men (65%), with early-stage disease (76% stage 0-II), and superficial spreading melanoma histology (39%). Older patients, compared with younger patients, were more likely to be men (65% versus 49%, p < 0.0001), and have in situ melanoma (28% versus 21%, p < 0.0001); less likely to have nodal metastases (7% versus 9%, p < 0.0001), receive care in academic centers (30% versus 35%, p < 0.0001), undergo wide excision or major amputation for stage I-III disease (68% versus 72%, p < 0.0001) and systemic therapy for stage III (18% versus 45%, p < 0.0001) and IV disease (30% versus 50%, p < 0.0001). Conclusion: Older patients with melanoma are less likely to receive care in academic centers, undergo wide excision for stage I-III disease and receive systemic therapy for stage III-IV disease. Particularly, the utilization of systemic therapy is markedly low. This disparity is particularly important with the availability of less intense more effective therapies. © The Author(s), 2014.
Thota R.,Creighton University |
Porter J.,Creighton University |
Ganti A.K.,87680 Nebraska Medical Center |
Peters E.,Creighton University
Journal of Thrombosis and Thrombolysis | Year: 2012
Severe hemodynamic collapse after knee surgery from bilateral adrenal hemorrhages is rare. Even rarer is it occurring from adrenal hemorrhage as a complication of heparin induced thrombocytopenia. Due to lack of awareness of this rare complication and associated complex scenario in critically ill patients, diagnosis is often made post mortem. A diagnosis of bilateral adrenal hemorrhage should be considered in any patient presenting with non-specific symptoms of fever, abdominal pain, confusion and rapid hemodynamic collapse not responding to standard therapy. This is crucial especially in the setting of heparin induced thrombocytopenia as thrombosis and not hemorrhage is often the most feared complication of this syndrome. © Springer Science+Business Media, LLC 2011.
Ganti A.K.,University of Nebraska Medical Center |
Ganti A.K.,87680 Nebraska Medical Center |
Siedlik E.,University of Nebraska Medical Center |
Siedlik E.,Creighton University |
And 3 more authors.
American Journal of Clinical Oncology: Cancer Clinical Trials | Year: 2011
Background: The effect of age and/or comorbidities on management decisions in lung cancer patients has been debated. The Charlson Comorbidity Index (CCI) was developed to help predict mortality from chronic medical conditions. This study was undertaken to evaluate whether CCI is correlated with survival in lung cancer. Patients and Methods: A retrospective chart review of 617 lung cancer patients diagnosed between 1994 and 2007 was conducted. CCI was calculated for each patient with and without the inclusion of age. Multivariate Cox proportional hazard regression analysis was used to evaluate the relationship between CCI and survival while adjusting for other prognostic factors. Results: Six patients were excluded from the final analysis due to missing outcome or comorbidity data. The median age at diagnosis was 64 years (range, 16-89 y). Five hundred fourteen patients (84%) had nonsmall cell lung cancer and 97 patients (16%) had small cell lung cancer. Using multivariate analysis, no correlation was found between CCI and risk of death whether or not age was included in the index score. Conclusions: CCI did not provide predictive validity for survival of lung cancer patients. Development of accurate and predictive prognostic models to help estimate a patient's prognosis is needed. Copyright © 2011 by Lippincott Williams & Wilkins.
Barber N.A.,87680 Nebraska Medical Center |
Loberiza Jr. F.R.,87680 Nebraska Medical Center |
Perry A.M.,University of Manitoba |
Bast M.,87680 Nebraska Medical Center |
And 7 more authors.
Clinical Lymphoma, Myeloma and Leukemia | Year: 2013
Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is often associated with concurrent or subsequent development of T-cell/histiocyte-rich large B-cell lymphoma (THR-LBCL). Distinguishing the two is important because their therapies are different. Functional imaging with PET/CT is used to stage both Hodgkin and non-Hodgkin lymphomas. Aggressive lymphomas are usually more PET avid than the indolent subtypes. Therefore, it is possible that PET/CT may help distinguish NLPHL from THR-LBCL. Patients and Methods: Herein, we retrospectively describe the clinical and PET/CT findings of 12 patients with NLPHL or THR-LBCL seen from 2004-2010. Results and Conclusions: Six patients each were identified and the average SUVmax was 6.9 (range, 5.7-7.3) in NLPHL and 16.6 (range, 4-29) in THR-LBCL (p = 0.055). Bone and extranodal involvement was found in one patient with NLPHL compared to four patients with THR-LBCL. This patient failed to respond to ABVD and was subsequently found to have THR-LBCL. We suggest that patients with NLPHL and THR-LBCL have different clinical and PET/CT characteristics. NLPHL patients had lower SUVmax on PET/CT compared to those with THR-LBCL. The presence of bone or extranodal involvement is more common in patients with THR-LBCL. Patients with NLPHL and an uncharacteristically higher SUVmax on PET/CT, or those with bone or extranodal involvement, should alert the clinician to consider the presence of THR-LBCL. © 2013 Elsevier Inc. All rights reserved.