Unknown

Dataset Information

0

Radiochemotherapy plus 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in advanced-stage cervical and vaginal cancers.


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 3-aminopyridine-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.

SUBMITTER: Kunos CA 

PROVIDER: S-EPMC4260802 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Radiochemotherapy plus 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in advanced-stage cervical and vaginal cancers.

Kunos Charles A CA   Radivoyevitch Tomas T   Waggoner Steven S   Debernardo Robert R   Zanotti Kristine K   Resnick Kimberly K   Fusco Nancy N   Adams Ramon R   Redline Raymond R   Faulhaber Peter P   Dowlati Afshin A  

Gynecologic oncology 20130418 1


<h4>Objective</h4>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.<h4>Methods</h4>We conducted a phase II study evaluating 3× weekly 2-hour intravenous 3-aminopyridine-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  ...[more]

Similar Datasets

| S-EPMC3288125 | biostudies-literature
| S-EPMC3059107 | biostudies-literature
| S-EPMC2921466 | biostudies-literature
| S-EPMC3374975 | biostudies-literature
| S-EPMC8797309 | biostudies-literature
| S-EPMC5949312 | biostudies-literature
| S-EPMC4730960 | biostudies-literature
| S-EPMC7521078 | biostudies-literature
| S-EPMC3014388 | biostudies-literature
| S-EPMC5531959 | biostudies-other