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Charles A. Kunos – One of the best experts on this subject based on the ideXlab platform.

  • radiochemotherapy plus 3 Aminopyridine 2 carboxaldehyde thiosemicarbazone 3 ap nsc 663249 in advanced stage cervical and vaginal cancers
    Gynecologic Oncology, 2013
    Co-Authors: Charles A. Kunos, Tomas Radivoyevitch, Steven E Waggoner, Kristine M Zanotti, Nancy Fusco, Ramon Adams, Robert Debernardo, Kimberly Resnick, Raymond W. Redline, Peter Faulhaber
    Abstract:

    Abstract Objective Cervical and vaginal cancers have virally-mediated or mutated defects in DNA damage repair responses, making these cancers sensible targets for ribonucleotide reductase inhibition during radiochemotherapy. Methods We conducted a phase II study evaluating 3× weekly 2-hour intravenous 3Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, 25mg/m 2 ) co-administered with 1× weekly intravenous cisplatin (40mg/m 2 ) and daily pelvic radiation (45Gy) in women with stage I B2 –IV B cervical (n=22) or stage II–IV vaginal (n=3) cancers. Brachytherapy followed (40Gy). Toxicity was monitored by common terminology criteria for adverse events (version 3.0). The primary end point of response was assessed by 3-month posttherapy 2-[ 18 F] fluoro-2-deoxy-d-gld-glucose positron emission tomography (PET/CT) and clinical examination. Results 3-AP radiochemotherapy achieved clinical responses in 24 (96% [95% confidence interval: 80–99%]) of 25 patients (median follow-up 20months, range 2–35months). 23 (96% [95% confidence interval: 80–99%]) of 24 patients had 3-month posttherapy PET/CT scans that recorded metabolic activity in the cervix or vagina equal or less than that of the cardiac blood pool, suggesting complete metabolic responses. The most frequent 3-AP radiochemotherapy-related adverse events included fatigue, nausea, diarrhea, and reversible hematological and electrolyte abnormalities. Conclusions The addition of 3-AP to cisplatin radiochemotherapy was tolerable and produced high rates of clinical and metabolic responses in women with cervical and vaginal cancers. Future randomized phase II and III clinical trials of 3-AP radiochemotherapy are warranted.

  • Radiochemotherapy plus 3Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in advanced-stage cervical and vaginal cancers ☆ ☆☆
    Gynecologic oncology, 2013
    Co-Authors: Charles A. Kunos, Tomas Radivoyevitch, Steven E Waggoner, Kristine M Zanotti, Nancy Fusco, Ramon Adams, Robert Debernardo, Kimberly Resnick, Raymond W. Redline, Peter Faulhaber
    Abstract:

    Cervical and vaginal cancers have virally-mediated or mutated defects in DNA damage repair responses, making these cancers sensible targets for ribonucleotide reductase inhibition during radiochemotherapy. We conducted a phase II study evaluating 3× weekly 2-hour intravenous 3Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, 25 mg/m(2)) co-administered with 1× weekly intravenous cisplatin (40 mg/m(2)) and daily pelvic radiation (45 Gy) in women with stage I(B2)-IV(B) cervical (n=22) or stage II-IV vaginal (n=3) cancers. Brachytherapy followed (40 Gy). Toxicity was monitored by common terminology criteria for adverse events (version 3.0). The primary end point of response was assessed by 3-month posttherapy 2-[(18)F] fluoro-2-deoxy-d-gld-glucose positron emission tomography (PET/CT) and clinical examination. 3-AP radiochemotherapy achieved clinical responses in 24 (96% [95% confidence interval: 80-99%]) of 25 patients (median follow-up 20 months, range 2-35 months). 23 (96% [95% confidence interval: 80-99%]) of 24 patients had 3-month posttherapy PET/CT scans that recorded metabolic activity in the cervix or vagina equal or less than that of the cardiac blood pool, suggesting complete metabolic responses. The most frequent 3-AP radiochemotherapy-related adverse events included fatigue, nausea, diarrhea, and reversible hematological and electrolyte abnormalities. The addition of 3-AP to cisplatin radiochemotherapy was tolerable and produced high rates of clinical and metabolic responses in women with cervical and vaginal cancers. Future randomized phase II and III clinical trials of 3-AP radiochemotherapy are warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

  • a phase i and pharmacokinetic study of oral 3 Aminopyridine 2 carboxaldehyde thiosemicarbazone 3 ap nsc 663249 in the treatment of advanced stage solid cancers a california cancer consortium study
    Cancer Chemotherapy and Pharmacology, 2012
    Co-Authors: Joseph Chao, Timothy W. Synold, Robert J. Morgan, Charles A. Kunos, Jeff Longmate, Heinz-josef Lenz, Dean Lim, Stephen Shibata, Vincent Chung, Ronald G. Stoller
    Abstract:

    Background 3Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) is a novel small-molecule ribonucleotide reductase inhibitor. This study was designed to estimate the maximum tolerated dose (MTD) and oral bioavailability of 3-AP in patients with advanced-stage solid tumors.

Steven E Waggoner – One of the best experts on this subject based on the ideXlab platform.

  • radiochemotherapy plus 3 Aminopyridine 2 carboxaldehyde thiosemicarbazone 3 ap nsc 663249 in advanced stage cervical and vaginal cancers
    Gynecologic Oncology, 2013
    Co-Authors: Charles A. Kunos, Tomas Radivoyevitch, Steven E Waggoner, Kristine M Zanotti, Nancy Fusco, Ramon Adams, Robert Debernardo, Kimberly Resnick, Raymond W. Redline, Peter Faulhaber
    Abstract:

    Abstract Objective Cervical and vaginal cancers have virally-mediated or mutated defects in DNA damage repair responses, making these cancers sensible targets for ribonucleotide reductase inhibition during radiochemotherapy. Methods We conducted a phase II study evaluating 3× weekly 2-hour intravenous 3Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, 25mg/m 2 ) co-administered with 1× weekly intravenous cisplatin (40mg/m 2 ) and daily pelvic radiation (45Gy) in women with stage I B2 –IV B cervical (n=22) or stage II–IV vaginal (n=3) cancers. Brachytherapy followed (40Gy). Toxicity was monitored by common terminology criteria for adverse events (version 3.0). The primary end point of response was assessed by 3-month posttherapy 2-[ 18 F] fluoro-2-deoxy-d-glucose positron emission tomography (PET/CT) and clinical examination. Results 3-AP radiochemotherapy achieved clinical responses in 24 (96% [95% confidence interval: 80–99%]) of 25 patients (median follow-up 20months, range 2–35months). 23 (96% [95% confidence interval: 80–99%]) of 24 patients had 3-month posttherapy PET/CT scans that recorded metabolic activity in the cervix or vagina equal or less than that of the cardiac blood pool, suggesting complete metabolic responses. The most frequent 3-AP radiochemotherapy-related adverse events included fatigue, nausea, diarrhea, and reversible hematological and electrolyte abnormalities. Conclusions The addition of 3-AP to cisplatin radiochemotherapy was tolerable and produced high rates of clinical and metabolic responses in women with cervical and vaginal cancers. Future randomized phase II and III clinical trials of 3-AP radiochemotherapy are warranted.

  • Radiochemotherapy plus 3Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in advanced-stage cervical and vaginal cancers ☆ ☆☆
    Gynecologic oncology, 2013
    Co-Authors: Charles A. Kunos, Tomas Radivoyevitch, Steven E Waggoner, Kristine M Zanotti, Nancy Fusco, Ramon Adams, Robert Debernardo, Kimberly Resnick, Raymond W. Redline, Peter Faulhaber
    Abstract:

    Cervical and vaginal cancers have virally-mediated or mutated defects in DNA damage repair responses, making these cancers sensible targets for ribonucleotide reductase inhibition during radiochemotherapy. We conducted a phase II study evaluating 3× weekly 2-hour intravenous 3Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, 25 mg/m(2)) co-administered with 1× weekly intravenous cisplatin (40 mg/m(2)) and daily pelvic radiation (45 Gy) in women with stage I(B2)-IV(B) cervical (n=22) or stage II-IV vaginal (n=3) cancers. Brachytherapy followed (40 Gy). Toxicity was monitored by common terminology criteria for adverse events (version 3.0). The primary end point of response was assessed by 3-month posttherapy 2-[(18)F] fluoro-2-deoxy-d-glucose positron emission tomography (PET/CT) and clinical examination. 3-AP radiochemotherapy achieved clinical responses in 24 (96% [95% confidence interval: 80-99%]) of 25 patients (median follow-up 20 months, range 2-35 months). 23 (96% [95% confidence interval: 80-99%]) of 24 patients had 3-month posttherapy PET/CT scans that recorded metabolic activity in the cervix or vagina equal or less than that of the cardiac blood pool, suggesting complete metabolic responses. The most frequent 3-AP radiochemotherapy-related adverse events included fatigue, nausea, diarrhea, and reversible hematological and electrolyte abnormalities. The addition of 3-AP to cisplatin radiochemotherapy was tolerable and produced high rates of clinical and metabolic responses in women with cervical and vaginal cancers. Future randomized phase II and III clinical trials of 3-AP radiochemotherapy are warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

  • phase ii trial of pelvic radiation weekly cisplatin and 3 Aminopyridine 2 carboxaldehyde thiosemicarbazone 3 ap nsc 663249 for locally advanced cervical and vaginal cancer
    Journal of Clinical Oncology, 2011
    Co-Authors: Charles A. Kunos, Tomas Radivoyevitch, Steven E Waggoner, Kristine M Zanotti, R Debernardo, Nancy Fusco, A Heugel, J Knazek, Ramon Adams, Afshin Dowlati
    Abstract:

    5034 Background: This on-going clinical trial assesses the safety and clinical activity of 3x weekly intravenous 3Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) co-administer…

Tomas Radivoyevitch – One of the best experts on this subject based on the ideXlab platform.

  • radiochemotherapy plus 3 Aminopyridine 2 carboxaldehyde thiosemicarbazone 3 ap nsc 663249 in advanced stage cervical and vaginal cancers
    Gynecologic Oncology, 2013
    Co-Authors: Charles A. Kunos, Tomas Radivoyevitch, Steven E Waggoner, Kristine M Zanotti, Nancy Fusco, Ramon Adams, Robert Debernardo, Kimberly Resnick, Raymond W. Redline, Peter Faulhaber
    Abstract:

    Abstract Objective Cervical and vaginal cancers have virally-mediated or mutated defects in DNA damage repair responses, making these cancers sensible targets for ribonucleotide reductase inhibition during radiochemotherapy. Methods We conducted a phase II study evaluating 3× weekly 2-hour intravenous 3Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, 25mg/m 2 ) co-administered with 1× weekly intravenous cisplatin (40mg/m 2 ) and daily pelvic radiation (45Gy) in women with stage I B2 –IV B cervical (n=22) or stage II–IV vaginal (n=3) cancers. Brachytherapy followed (40Gy). Toxicity was monitored by common terminology criteria for adverse events (version 3.0). The primary end point of response was assessed by 3-month posttherapy 2-[ 18 F] fluoro-2-deoxy-d-glucose positron emission tomography (PET/CT) and clinical examination. Results 3-AP radiochemotherapy achieved clinical responses in 24 (96% [95% confidence interval: 80–99%]) of 25 patients (median follow-up 20months, range 2–35months). 23 (96% [95% confidence interval: 80–99%]) of 24 patients had 3-month posttherapy PET/CT scans that recorded metabolic activity in the cervix or vagina equal or less than that of the cardiac blood pool, suggesting complete metabolic responses. The most frequent 3-AP radiochemotherapy-related adverse events included fatigue, nausea, diarrhea, and reversible hematological and electrolyte abnormalities. Conclusions The addition of 3-AP to cisplatin radiochemotherapy was tolerable and produced high rates of clinical and metabolic responses in women with cervical and vaginal cancers. Future randomized phase II and III clinical trials of 3-AP radiochemotherapy are warranted.

  • Radiochemotherapy plus 3Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in advanced-stage cervical and vaginal cancers ☆ ☆☆
    Gynecologic oncology, 2013
    Co-Authors: Charles A. Kunos, Tomas Radivoyevitch, Steven E Waggoner, Kristine M Zanotti, Nancy Fusco, Ramon Adams, Robert Debernardo, Kimberly Resnick, Raymond W. Redline, Peter Faulhaber
    Abstract:

    Cervical and vaginal cancers have virally-mediated or mutated defects in DNA damage repair responses, making these cancers sensible targets for ribonucleotide reductase inhibition during radiochemotherapy. We conducted a phase II study evaluating 3× weekly 2-hour intravenous 3Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, 25 mg/m(2)) co-administered with 1× weekly intravenous cisplatin (40 mg/m(2)) and daily pelvic radiation (45 Gy) in women with stage I(B2)-IV(B) cervical (n=22) or stage II-IV vaginal (n=3) cancers. Brachytherapy followed (40 Gy). Toxicity was monitored by common terminology criteria for adverse events (version 3.0). The primary end point of response was assessed by 3-month posttherapy 2-[(18)F] fluoro-2-deoxy-d-glucose positron emission tomography (PET/CT) and clinical examination. 3-AP radiochemotherapy achieved clinical responses in 24 (96% [95% confidence interval: 80-99%]) of 25 patients (median follow-up 20 months, range 2-35 months). 23 (96% [95% confidence interval: 80-99%]) of 24 patients had 3-month posttherapy PET/CT scans that recorded metabolic activity in the cervix or vagina equal or less than that of the cardiac blood pool, suggesting complete metabolic responses. The most frequent 3-AP radiochemotherapy-related adverse events included fatigue, nausea, diarrhea, and reversible hematological and electrolyte abnormalities. The addition of 3-AP to cisplatin radiochemotherapy was tolerable and produced high rates of clinical and metabolic responses in women with cervical and vaginal cancers. Future randomized phase II and III clinical trials of 3-AP radiochemotherapy are warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

  • management of 3 Aminopyridine 2 carboxaldehyde thiosemicarbazone induced methemoglobinemia
    Future Oncology, 2012
    Co-Authors: Charles A. Kunos, Tomas Radivoyevitch, Stephen T Ingalls, Charles L Hoppel
    Abstract:

    The anticancer agent 3Aminopyridine-2-carboxaldehyde thiosemicarbazone is a ribonucleotide reductase inhibitor. It inactivates ribonucleotide reductase by disrupting an iron-stabilized radical in ribonucleotide reductase’s small subunits, M2 and M2b (p53R2). Unfortunately, 3Aminopyridine-2-carboxaldehyde thiosemicarbazone also alters iron II (Fe2+) in hemoglobin. This creates Fe3+ methemoglobin that does not deliver oxygen. Fe2+ in hemoglobin normally auto-oxidizes to inactive Fe3+ methemoglobin at a rate of nearly 3% per day and this is counterbalanced by a reductase system that normally limits methemoglobin concentrations to less than 1% of hemoglobin. This balance may be perturbed by symptomatic toxicity levels during 3Aminopyridine-2-carboxaldehyde thiosemicarbazone therapy. Indications of 3Aminopyridine-2-carboxaldehyde thiosemicarbazone sequelae attributable to methemoglobinemia include resting dyspnea, headaches and altered cognition. Management of methemoglobinemia includes supplemental oxygen…