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Park Ridge, IL, United States

Samuels B.L.,Kootenai Cancer Center | Chawla S.,Sarcoma Oncology Center | Patel S.,University of Houston | von Mehren M.,Chase Medical | And 5 more authors.
Annals of Oncology | Year: 2013

Background: This expanded access program (EAP) was designed to provide trabectedin access for patients with incurable soft tissue sarcoma (STS) following progression of disease with standard therapy. The outcomes of trial participants accrued over approximately 5 years are reported. Patients and methods: Adult patients with advanced STS of multiple histologies, including leiomyosarcoma and liposarcoma (L-sarcomas), following relapse or disease progression following standard-of-care chemotherapy, were enrolled. Trabectedin treatment cycles (1.5 mg/m2, intravenously over 24 h) were repeated q21 days. Objective response, overall survival (OS), and safety were evaluated. Results: Of 1895 patients enrolled, 807 (43%) had evaluable objective response data, with stable disease reported in 343 (43%) as best response. L-sarcoma patients exhibited longer, OS compared with other histologies [16.2 months (95% confidence interval (CI) 14.1-19.5) versus 8.4 months (95% CI 7.1-10.7)], and a slightly higher objective response rate [6.9% (95% CI 4.8-9.6) versus 4.0% (95% CI 2.1-6.8)]. The median treatment duration was 70 days representing a median of three treatment cycles; 30% of patients received ≥6 cycles. Safety and tolerability in this EAP were consistent with prior clinical trial data. Conclusion: Results of this EAP are consistent with previous reports of trabectedin, demonstrating disease control despite a low incidence of objective responses in advanced STS patients after failure of standard chemotherapy. ClinicalTrials.gov: NCT00210665. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Source

Dressel A.,University of Michigan | Kwari M.,University of Texas M. D. Anderson Cancer Center | McGreal A.M.,Oncology Specialists
Clinical Journal of Oncology Nursing | Year: 2011

Despite improvements in treatment, the outcome for some adult patients with acute or chronic leukemias remains poor. Clofarabine, a second-generation purine nucleoside analog, received U.S. Food and Drug Administration approval in 2004 for the treatment of pediatric patients with relapsed or refractory acute lymphocytic leukemia after at least two previous regimens. In addition, clinical studies have shown encouraging safety and efficacy results with clofarabine in the treatment of adult patients with various hematologic malignancies. Although most adult patients with leukemia receive the first course of clofarabine while hospitalized, many can be subsequently treated as outpatients with proper monitoring, support, and education. The most frequent side effects associated with clofarabine are gastrointestinal-related, myelosuppression, hepatotoxicity, renal dysfunction, and anorexia. Careful patient monitoring is essential to ensure early identification and prompt intervention. Younger patients and those of any age with no comorbid health issues, good performance status, and an adequate support network are more likely to tolerate outpatient clofarabine administration. Early identification and proactive pharmacologic and nonpharmacologic interventions may reduce the severity of these toxicities and prevent their progression. Patient education about strategies for prevention and management of symptoms also is essential. Source

Warso M.A.,MC | Richards J.M.,Oncology Specialists | Mehta D.,MC | Christov K.,MC | And 7 more authors.
British Journal of Cancer | Year: 2013

Background: This first-in-human, phase I clinical trial of p28 (NSC745104), a 28-amino-acid fragment of the cupredoxin azurin, investigated the safety, tolerability, pharmacokinetics and preliminary activity of p28 in patients with p53 + metastatic solid tumours. Methods: A total of 15 patients were administered p28 i.v. as a short infusion three times per week for 4 weeks followed by a 2-week rest under an accelerated titration 3+3 dose escalation design until either a grade 3-related adverse event occurred or the maximum tolerated dose (MTD) was reached. Single-dose and steady-state serum pharmacokinetics were characterised. Assessments included toxicity, best objective response by RECIST 1.1 Criteria, and overall survival.Results:No patients exhibited any dose-limiting toxicities (DLTs), significant adverse events or exhibited an immune response (IgG) to the peptide. The No Observed Adverse Effect Level (NOAEL) and MTD were not reached. Seven patients demonstrated stable disease for 7-61 weeks, three a partial response for 44-125 weeks, and one a complete response for 139 weeks. Three patients are still alive at 158, 140, and 110 weeks post therapy completion. Conclusion: p28 was tolerated with no significant adverse events. An MTD was not reached. Evidence of anti-tumour activity indicates a highly favourable therapeutic index and demonstrates proof of concept for this new class of non-HDM2-mediated peptide inhibitors of p53 ubiquitination. © 2013 Cancer Research UK. All rights reserved. Source

Hersey P.,Newcastle Melanoma Unit | Sosman J.,Vanderbilt Ingram Cancer Center | O'Day S.,Cancer Institute Medical Group | Richards J.,Oncology Specialists | And 8 more authors.
Cancer | Year: 2010

BACKGROUND: The alpha v beta 3 (α vβ3) integrin is involved in intracellular signaling regulating cell proliferation, migration, and differentiation and is important for tumor-induced angiogenesis. METHODS: This phase 2, randomized, open-label, 2-arm study was designed to capture safety data and evaluate the antitumor efficacy of etaracizumab (Abegrin), an IgG1 humanized monoclonal antibody against the αvβ3 integrin, in patients with previously untreated metastatic melanoma. The objective was to evaluate whether etaracizumab ± dacarbazine had sufficient clinical activity to warrant further study in a phase 3 clinical trial. RESULTS: One hundred twelve patients were randomized to receive etaracizumab alone (N = 57) or etaracizumab + dacarbazine (N = 55). Safety of etaracizumab ± dacarbazine was acceptable with infusion-related, gastrointestinal, and metabolic reactions being the most common adverse events (AEs). The majority of AEs were grade 1 or 2 in severity in both study arms; most events were not considered serious, except for cardiovascular (myocardial infarction, atrial fibrillation) and thromboembolic events, which occurred in 3 and 5 patients, respectively. None of the patients in the etaracizumab-alone study arm and 12.7% of patients in the etaracizumab + dacarbazine study arm achieved an objective response. The median duration of objective response in the etaracizumab + dacarbazine study arm was 4.2 months. Stable disease rate, time to progression (TTP), and progression-free survival (PFS) appeared to be similar between the 2 treatment arms. Stable disease occurred in 45.6% of patients in the etaracizumab-alone study arm and 40.0% of patients in the etaracizumab + dacarbazine study arm. Median TTP and median PFS were both 1.8 months in the etaracizumab-alone study arm and 2.5 and 2.6 months in the etaracizumab + dacarbazine study arm, respectively. Median overall survival was 12.6 months in the etaracizumab-alone study arm and 9.4 months in the etaracizumab + dacarbazine study arm. CONCLUSIONS: The survival results in both treatment arms of this study were considered unlikely to result in clinically meaningful improvement over dacarbazine alone. © 2010 American Cancer Society. Source

Schwartzentruber D.J.,Health Goshen Center for Cancer Care | Lawson D.H.,Emory University | Richards J.M.,Oncology Specialists | Conry R.M.,University of Alabama at Birmingham | And 21 more authors.
New England Journal of Medicine | Year: 2011

BACKGROUND: Stimulating an immune response against cancer with the use of vaccines remains a challenge. We hypothesized that combining a melanoma vaccine with interleukin-2, an immune activating agent, could improve outcomes. In a previous phase 2 study, patients with metastatic melanoma receiving high-dose interleukin-2 plus the gp100:209-217(210M) peptide vaccine had a higher rate of response than the rate that is expected among patients who are treated with interleukin-2 alone. METHODS: We conducted a randomized, phase 3 trial involving 185 patients at 21 centers. Eligibility criteria included stage IV or locally advanced stage III cutaneous melanoma, expression of HLA*A0201, an absence of brain metastases, and suitability for high-dose interleukin-2 therapy. Patients were randomly assigned to receive interleukin-2 alone (720,000 IU per kilogram of body weight per dose) or gp100:209-217(210M) plus incomplete Freund's adjuvant (Montanide ISA-51) once per cycle, followed by interleukin-2. The primary end point was clinical response. Secondary end points included toxic effects and progression-free survival. RESULTS: The treatment groups were well balanced with respect to baseline characteristics and received a similar amount of interleukin-2 per cycle. The toxic effects were consistent with those expected with interleukin-2 therapy. The vaccine-interleukin-2 group, as compared with the interleukin-2-only group, had a significant improvement in centrally verified overall clinical response (16% vs. 6%, P = 0.03), as well as longer progression-free survival (2.2 months; 95% confidence interval [CI], 1.7 to 3.9 vs. 1.6 months; 95% CI, 1.5 to 1.8; P = 0.008). The median overall survival was also longer in the vaccine-interleukin-2 group than in the interleukin-2-only group (17.8 months; 95% CI, 11.9 to 25.8 vs. 11.1 months; 95% CI, 8.7 to 16.3; P = 0.06). CONCLUSIONS: In patients with advanced melanoma, the response rate was higher and progression-free survival longer with vaccine and interleukin-2 than with interleukin-2 alone. Copyright © 2011 Massachusetts Medical Society. All rights reserved. Source

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