Journal article
Phase 1b/2a Trial of the Superoxide Dismutase Mimetic GC4419 to Reduce Chemoradiotherapy-Induced Oral Mucositis in Patients With Oral Cavity or Oropharyngeal Carcinoma
International journal of radiation oncology, biology, physics, Vol.100(2), pp.427-435
02/01/2018
DOI: 10.1016/j.ijrobp.2017.10.019
PMCID: PMC6430109
PMID: 29174131
Abstract
To assess the safety of the superoxide dismutase mimetic GC4419 in combination with radiation and concurrent cisplatin for patients with oral cavity or oropharyngeal cancer (OCC) and to assess the potential of GC4419 to reduce severe oral mucositis (OM).
Patients with locally advanced OCC treated with definitive or postoperative intensity modulated radiation therapy (IMRT) plus cisplatin received GC4419 by 60-minute intravenous infusion, ending <60 minutes before IMRT, Monday through Friday for 3 to 7 weeks, in a dose and duration escalation study. Oral mucositis was assessed twice weekly during and weekly after IMRT.
A total of 46 patients received GC4419 in 11 separate dosing and duration cohorts: dose escalation occurred in 5 cohorts receiving 15 to 112 mg/d over 3 weeks (n=20), duration escalation in 3 cohorts receiving 112 mg/d over 4 to 6 weeks (n=12), and then 3 additional cohorts receiving 30 or 90 mg/d over 6 to 7 weeks (n=14). A maximum tolerated dose was not reached. One dose-limiting toxicity (grade 3 gastroenteritis and vomiting with hyponatremia) occurred in each of 2 separate cohorts at 112 mg. Nausea/vomiting and facial paresthesia during infusion seemed to be GC4419 dose–related. Severe OM occurred through 60 Gy in 4 of 14 patients (29%) dosed for 6 to 7 weeks, with median duration of only 2.5 days.
The safety of GC4419 concurrently with chemoradiation for OCC was acceptable. Toxicities included nausea/vomiting and paresthesia. Doses of 30 and 90 mg/d administered for 7 weeks were selected for further study. In an exploratory analysis, severe OM seemed less frequent and briefer than expected.
Details
- Title: Subtitle
- Phase 1b/2a Trial of the Superoxide Dismutase Mimetic GC4419 to Reduce Chemoradiotherapy-Induced Oral Mucositis in Patients With Oral Cavity or Oropharyngeal Carcinoma
- Creators
- Carryn M Anderson - Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, IowaStephen T Sonis - Biomodels and Division of Oral Medicine, Dana-Farber Cancer Institute, Boston, MassachusettsChristopher M Lee - Cancer Care NorthwestDouglas Adkins - Section of Medical Oncology, Washington University School of Medicine, St. Louis, MissouriBryan G Allen - Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, IowaWenqing Sun - Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, IowaSanjiv S Agarwala - Department of Medical Oncology, St. Luke's University Hospital and Temple University, Easton, PennsylvaniaMadhavi L Venigalla - Lakeland Regional Health Cancer Center, Lakeland, FloridaYuhchyau Chen - Department of Radiation Oncology, Wilmot Cancer Institute, University of Rochester, Rochester, New YorkWeining Zhen - Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NebraskaDiane R Mould - Projections Research Inc., Phoenixville, PennsylvaniaJon T Holmlund - Galera Therapeutics, Inc., Malvern, PennsylvaniaJeffrey M Brill - Galera Therapeutics, Inc., Malvern, PennsylvaniaJohn M Buatti - Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- International journal of radiation oncology, biology, physics, Vol.100(2), pp.427-435
- DOI
- 10.1016/j.ijrobp.2017.10.019
- PMID
- 29174131
- PMCID
- PMC6430109
- NLM abbreviation
- Int J Radiat Oncol Biol Phys
- ISSN
- 0360-3016
- eISSN
- 1879-355X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 02/01/2018
- Academic Unit
- Radiation Oncology; Neurosurgery; Otolaryngology
- Record Identifier
- 9984046820802771
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