Thomas A. Dahl
Covance
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Thomas A. Dahl.
Journal of Immunotherapy | 2004
Yoo-Joung Ko; Glenn J. Bubley; Robert Weber; Charles H. Redfern; Daniel P. Gold; Lothar Finke; Andreas Kovar; Thomas A. Dahl; Stephen D. Gillies
Abstract: This phase 1 clinical trial was conducted to evaluate the safety and to determine the maximum tolerated dose (MTD) of the immunocytokine EMD 273066 huKS-IL2 and, secondarily, to assess its pharmacokinetics, immunogenic potential, and immunologic activity in patients with androgen-independent prostate cancer (n = 22). EMD 273066 was administered in 3-day cycles (separated by 4 weeks) of once-daily, 4-hour intravenous infusions at a dose determined by an escalation protocol (0.4, 0.7, 1.4, 2.8, 4.3, 6.4, or 8.5 mg/m2/d). Approximately 2/3 of patients received a second cycle of treatment. The results show that the MTD of EMD 273066 [ie, one dose level below that producing dose-limiting toxicity (DLT) in at least 33% of patients in a dosing group] was 6.4 mg/m2/d. EMD 273066 was generally well tolerated up to a dose of 4.3 mg/m2/d. No DLTs, defined as drug-related toxicities ≥ Grade 3 occurring during the first treatment cycle, were observed among patients in the 0.4-, 0.7-, 1.4-, or 4.3-mg/m2/d dosing groups. Four patients treated with 2.8, 6.4, or 8.5 mg/m2/d EMD 273066 experienced DLTs. Titers of both antiimmunocytokine and anti-FcIL-2 antibody responses were observed after the first dose cycle and either decreased or remained stable during a second course of treatment. No hypersensitivity reactions were observed. EMD 273066 exhibited immunologic activity as demonstrated by increases in lymphocyte counts, natural killer cell number and specific activity, and antibody-dependent cellular cytotoxicity activity. On average, Cmax, which was dose-dependent, was achieved within 1 hour after infusion. Mean t½, which was independent of dose, ranged from 4.0 to 6.7 hours across doses. A zero-compartment body model with one-order kinetics best described the concentration-time profiles. These data demonstrate that the novel immunocytokine EMD 273066 is well tolerated at doses above a level of observed systemic biologic activity in patients with androgen-independent prostate cancer.
Clinical Cancer Research | 2007
Anna Berkenblit; Joseph Paul Eder; David P. Ryan; Michael V. Seiden; Noriaki Tatsuta; Matthew L. Sherman; Thomas A. Dahl; Bruce J. Dezube; Jeffrey G. Supko
Purpose: STA-4783 is a new compound that markedly enhances the therapeutic index of paclitaxel against human tumor xenograft models. A phase I clinical trial was undertaken to determine the maximum tolerated dose, toxicity profile, and pharmacokinetics of STA-4783 in combination with paclitaxel. Experimental Design: Adults with refractory solid tumors concurrently received STA-4783 and paclitaxel as a 3-h i.v. infusion at starting doses of 44 and 135 mg/m2, respectively. After increasing paclitaxel to 175 mg/m2, the STA-4783 dose was escalated as permitted by dose-limiting toxicity during the first 21-day cycle. Results: Thirty-five patients were treated with eight dose levels of STA-4783/paclitaxel. In patients receiving 175 mg/m2 paclitaxel, the incidence of severe toxicity increased with escalation of the STA-4783 dose above 263 mg/m2, and 438 mg/m2 was the maximum tolerated dose. All toxicities were typical of paclitaxel, with neutropenia, mucositis, and myalgia/arthralgia being dose limiting. Partial responses were achieved in one patient with Kaposis sarcoma and another with ovarian cancer that progressed during prior treatment with paclitaxel. STA-4783 exhibited linear pharmacokinetics characterized by rapid elimination from plasma (biological half-life, 1.06 ± 0.24 h) and a low steady-state apparent volume of distribution (25.1 ± 8.1 L/m2). The total body clearance of paclitaxel decreased significantly with escalation of the STA-4783 dose. Conclusions: The STA-4783/paclitaxel combination was well tolerated with a toxicity profile similar to single-agent paclitaxel. Enhanced systemic exposure to paclitaxel resulting from a dose-dependent interaction with STA-4783 was associated with increased toxicity. Objective responses in two heavily pretreated patients, both with taxane exposure, have encouraged further clinical evaluation of this regimen.
The Journal of Infectious Diseases | 2000
Bruce J. Dezube; Thomas A. Dahl; Thomas K. Wong; Beryl Chapman; Mitsunori Ono; Naoto Yamaguchi; Stephen D. Gillies; Lan Bo Chen; Clyde S. Crumpacker
FP-21399 is a bis(disulfonaphthalene) derivative that prevents human immunodeficiency virus (HIV) infection of uninfected cells by blocking entry of the virus. FP-21399 shows an affinity for lymph nodes. In this phase I study, FP-21399 was administered intravenously over 1 h as a single dose (0.9, 1.7, 2.8, and 4.2 mg/kg) or as a once-weekly infusion (1, 2, and 3 mg/kg) for 4 consecutive weeks to 34 HIV-1 infected patients with CD4(+) cell counts of 50-400 cells/microL. Concomitant antiretroviral therapy was permitted but not required. The most frequent adverse events involved the transient, dose-dependent appearance of drug- or metabolite-related color in the urine and skin. Plasma drug levels were linear with dose. The drug was cleared, with an elimination half-life of 4 h and a terminal half-life of 1.5-2 days; the terminal half-life represented redistribution and clearance from tissues. FP-21399 administered weekly for 4 weeks was well tolerated. Further studies are necessary to define the role of this fusion inhibitor in the treatment of HIV infection.
The Journal of Infectious Diseases | 2004
Benjamin E. Gewurz; Mark Jacobs; Jo Ann Proper; Thomas A. Dahl; Tamio Fujiwara; Bruce J. Dezube
Capravirine is a nonnucleoside reverse-transcriptase inhibitor (NNRTI) with a unique resistance profile. Although single mutations allow resistance to established NNRTIs, human immunodeficiency virus (HIV)-1 must undergo multiple mutations to achieve resistance to capravirine. In the present phase 1 study, capravirine was administered orally for up to 28 days to 55 HIV-1-infected individuals with CD4+ T lymphocyte counts of 50-500 cells/microL. The most frequent adverse events were diarrhea (5%) and nausea (4%), with no drug-related rashes observed. The day 15 median (mean) HIV-1 load decreased by 1.34 (1.45) log(10) copies/mL in the patients receiving 25 mg/kg/day. Capravirine demonstrated potent antiviral activity, even in antiretroviral-experienced patients.
Clinical Cancer Research | 2002
Stephen D. Gillies; Kin-Ming Lo; Christa Burger; Yan Lan; Thomas A. Dahl; Wai-Keung Wong
Archive | 2006
Thomas A. Dahl; Matthew Mcleod
Archive | 2006
James Barsoum; Zhenjian Du; Thomas A. Dahl; Matthew Mcleod
Journal of Clinical Oncology | 2004
Ravi Salgia; Anna Berkenblit; Bruce J. Dezube; Thomas A. Dahl; K. Koya
Archive | 2006
James Barsoum; Zhenjian Du; Thomas A. Dahl; Matthew Mcleod
Journal of Clinical Oncology | 2005
Anna Berkenblit; Jeffrey G. Supko; David P. Ryan; Michael V. Seiden; M. Nagai; J. Bertin; Thomas A. Dahl; Bruce J. Dezube; Joseph Paul Eder