Journal article
Dose finding, bioavailability, and PK-PD of oral triapine with concurrent chemoradiation for locally advanced cervical cancer and vaginal cancer (ETCTN 9892)
Cancer chemotherapy and pharmacology, v 95(1), p4
01 Dec 2025
PMID: 39673591
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background
The addition of IV triapine to chemoradiation appeared active in phase I and II studies but drug delivery is cumbersome. We examined PO triapine with cisplatin chemoradiation.
Methods
We implemented a 3 + 3 design for PO triapine dose escalation with expansion, starting at 100 mg, five days a week for five weeks while receiving radiation with weekly IV cisplatin for locally advanced cervical or vaginal cancer. Maximum tolerated dose (MTD), dose limiting toxicity (DLT), adverse events, pharmacokinetics (PK), pharmacodynamics (PD), and metabolic complete response (mCR) were assessed.
Results
19/21 patients were DLT evaluable. DLTs included grade 4 neutropenia (
n
= 2), leukopenia (
n
= 2), lymphopenia (
n
= 2), and hypokalemia (
n
= 1). Grade 3 toxicities at least possibly related were as expected for cisplatin chemoradiation: lymphopenia (
n
= 12), anemia (
n
= 10), neutropenia (
n
= 4), leukopenia (
n
= 8), decreased platelets (
n
= 2), hypertension (
n
= 1), and hyponatremia (
n
= 1). MTD and RP2D were established at 100 mg. 8/13 evaluable patients had a mCR. Triapine had a bioavailability of 59%. Methemoglobin levels correlated with triapine exposure. Smoking almost doubled CYP1A2 mediated triapine clearance.
Conclusions
Oral triapine is safe when given with cisplatin chemoradiation, convenient, bioavailable. Exposure is negatively impacted by smoking, and methemoglobin is a biomarker of exposure.
Clinical trial registration
NCT02595879.
Metrics
9 Record Views
Details
- Title
- Dose finding, bioavailability, and PK-PD of oral triapine with concurrent chemoradiation for locally advanced cervical cancer and vaginal cancer (ETCTN 9892)
- Creators
- Sarah E. Taylor - University of PittsburghSarah Behr - UPMC Hillman Cancer CenterKristine L. Cooper - UPMC Hillman Cancer CenterHaider Mahdi - University of PittsburghDenise Fabian - Markey Cancer CenterHolly Gallion - Markey Cancer CenterFrederick Ueland - Markey Cancer CenterJohn Vargo - UPMC Hillman Cancer CenterBrian Orr - University of PittsburghEugenia Girda - Rutgers, The State University of New JerseyMadeleine Courtney-Brooks - University of PittsburghAlexander B. Olawaiye - University of PittsburghLeslie M. Randall - Virginia Commonwealth UniversityDebra L. Richardson - University of Oklahoma Health Sciences CenterStephanie A. Sullivan - Virginia Commonwealth UniversityMarilyn Huang - University of VirginiaSusan M. Christner - UPMC Hillman Cancer CenterSushil Beriwal - UPMC Hillman Cancer CenterYan Lin - UPMC Hillman Cancer CenterAman Chauhan - Sylvester Comprehensive Cancer CenterEdward Chu - Montefiore Medical CenterElise C. Kohn - National Cancer InstituteCharles Kunos - Sylvester Comprehensive Cancer CenterS. Percy Ivy - National Cancer InstituteJan H. Beumer - University of Pittsburgh
- Publication Details
- Cancer chemotherapy and pharmacology, v 95(1), p4
- Publisher
- Springer Berlin Heidelberg; NEW YORK
- Number of pages
- 12
- Grant note
- UM1CA186690; P30CA047904; P30CA047904; U24CA247643 / national cancer institute
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Radiation Oncology (and Nuclear Medicine)
- Web of Science ID
- WOS:001379091400001
- Scopus ID
- 2-s2.0-85211898238
- Other Identifier
- 991022004881304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Oncology
- Pharmacology & Pharmacy