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Baltimore Highlands, MD, United States

Keizman D.,Sidney Kimmel Comprehensive Cancer Center | Zahurak M.,Sidney Kimmel Comprehensive Cancer Center | Sinibaldi V.,Sidney Kimmel Comprehensive Cancer Center | Carducci M.,Sidney Kimmel Comprehensive Cancer Center | And 7 more authors.
Clinical Cancer Research | Year: 2010

Purpose: To evaluate the safety and activity of 6 months of treatment with lenalidomide at 5 or 25 mg/d in nonmetastatic biochemically relapsed prostate cancer. Experimental Design: Sixty men with non-castrate, nonmetastatic, biochemically relapsed prostate cancer were stratified by prostate-specific antigen (PSA) doubling time, surgery/radiation therapy, prior androgen deprivation therapy (ADT), and randomized to lenalidomide 5 mg (n = 26) or 25 mg/d (n = 34) for 3 weeks repeated monthly for 6 months or until dose-limiting toxicity or disease progression. Toxicity was evaluated monthly, and PSAs and X-rays/scans every 6 months. Study size was determined to detect a progression rate of 40% at 6 months in either arm with 85% power (compared with a rate of 80% in the population receiving no treatment). Changes in PSA slopes were calculated using the regression of the log PSA for each patient before and during the initial 6 months and compared by t test. Results: Baseline variables were balanced between arms. Grade 3/4 toxicity rates were 12% (n = 3) with 5 mg and 29% (n = 10) with 25 mg (P = 0.1), most commonly neutropenia (five patients, all on 25 mg). Two patients per arm had thromboembolic events. The change in PSA slope was greater with 25 mg versus 5 mg [-0.172 (-0.24 to -0.11) versus -0.033 (-0.11 to 0.04); P = 0.005]. With a mean follow-up of 31.4 months (range 14-44), five patients on 25 mg and one patient on 5 mg remain on the study. Conclusions: Lenalidomide has acceptable toxicity and is associated with long-term disease stabilization and PSA declines. Randomized studies evaluating conventional clinical disease end points in this patient population are planned. ©2010 AACR.

Keizman D.,Sidney Kimmel Comprehensive Cancer Center | Eisenberger M.,Bunting Blaustein Cancer Research Building
Current Opinion in Supportive and Palliative Care | Year: 2010

Purpose of review Prognostic clinical, pathological, and molecular parameters identify patients with nonmetastatic prostate cancer that are at risk for the development of future metastatic disease and shorter survival. In metastatic castration-resistant prostate cancer, docetaxel-based chemotherapy prolongs survival and improves quality of life, and is the standard of care. It may be rational to hypothesize that early utilization of chemotherapy may delay the onset of distant metastasis and prolong survival in the earlier nonmetastatic disease. A discussion on ongoing clinical trials and natural history aspects applicable to clinical trials design in this setting are presented herein. Recent findings Preliminary data suggest that chemotherapy is well tolerated, feasible, and potentially active in nonmetastatic prostate cancer. However, results from prospective randomized trials were not published yet. Summary In nonmetastatic prostate cancer, application of chemotherapy remains an open question awaiting prospective validation and should be routinely applied outside of clinical trials. In view of the long natural history, evaluation of conventional endpoints as time to distant metastasis and survival are challenging even in the high-risk patients. Appropriate patient selection based on predictive biomarkers and surrogate endpoints may provide critical information for patient selection and study design. Copyright © Lippincott Williams & Wilkins.

Kelly R.J.,Bunting Blaustein Cancer Research Building
JNCCN Journal of the National Comprehensive Cancer Network | Year: 2013

A better understanding of the biology of both thymomas and thymic carcinomas has occurred in recent years thanks to advanced technologies such as comparative genomic hybridization, expression array analysis, and next-generation sequencing. Gene expression profiling and genomic clustering studies have shown that thymic tumors as classified by the 2004 WHO system do have different molecular features. Because of the rarity of these tumors, there is a paucity of high-quality clinical research data, and treatment decisions are often guided by the small amount of prospective trial data, retrospective series, and individual case reports. The literature does report on several advanced thymic tumors that have responded to new targeted agents, indicating that across the spectrum of thymic malignancies there may be clinically relevant molecular subsets. Genomic profiling distinguishes type B3 thymoma and thymic carcinoma from type A and B2 thymomas. Furthermore, type B2 thymomas can be separated from other subgroups in that it has a more distinctly lymphocytic component than the other groups in which epithelial cells predominate. The presence of KIT mutations in thymic carcinomas rather than in thymomas further adds to a growing body of evidence showing that underlying tumor biology may in the future lead to molecular classifications, which may enhance therapies for these rare tumors. Copyright © 2013 by the National Comprehensive Cancer Network. All rights reserved.

Doan N.T.Q.,Copenhagen University | Paulsen E.S.,Copenhagen University | Sehgal P.,University of Aarhus | Moller J.V.,University of Aarhus | And 5 more authors.
Steroids | Year: 2015

The skin irritating principle from Thapsia garganica was isolated, named thapsigargin and the structure elucidated. By inhibiting the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) thapsigargin provokes apoptosis in almost all cells. By conjugating thapsigargin to peptides, which are only substrates for either prostate specific antigen (PSA) or prostate specific membrane antigen (PSMA) prodrugs were created, which selectively affect prostate cancer cells or neovascular tissue in tumors. One of the prodrug is currently tested in clinical phase II. The prodrug under clinical trial has been named mipsagargin ©2014 Elsevier Inc. All rights reserved.

Okuno S.,Rochester College | Bailey H.,University of Wisconsin - Madison | Mahoney M.R.,Rochester College | Adkins D.,University of Washington | And 4 more authors.
Cancer | Year: 2011

BACKGROUND: The primary goal of this trial was to evaluate the confirmed response rate of temsirolimus (CCI-779), a mammalian target of rapamycin in patients with advanced soft tissue sarcomas (STS). METHODS: Patients ≥18 years with measurable advanced STS, no prior chemotherapy for metastatic disease (adjuvant and neoadjuvant chemotherapy allowed), adequate organ function, and performance status of ≤2 were eligible. After premedication with an antihistamine, CCI-779 was given intravenously at 25 mg over 30 minutes on Days 1, 8, 15, and 22, repeated every 4 weeks. The primary endpoint was confirmed response rate per Response Evaluation Criteria in Solid Tumors. RESULTS: Between June 2004 and November 2005, a total of 41 patients were enrolled and began treatment; 40 patients are evaluable for response and adverse events. The median age was 62 years (range, 28-72 years) with 56% women. Eighty percent had high-grade STS, and 22% had prior adjuvant chemotherapy. There were 2 patients (5%; 95% confidence interval [CI], 1-17) (undifferentiated fibrosarcoma and uterine leiomyosarcoma) who achieved a confirmed partial response lasting 3 and 17 months, respectively. Thirty-nine (95%) patients have progressed, with a median time to progression of 2.0 months (95% CI, 1.8-3.5). The median overall survival was 7.6 months (95% CI, 6.1-15.9). Forty-three percent experienced grade 3+ adverse events that were possibly related to therapy. CONCLUSIONS: Temsirolimus in this patient population of STS had limited clinical activity and had moderate toxicities. © 2011 American Cancer Societyy.

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