Document Type
Article
Publication Date
12-1-2019
Abstract
PURPOSE: Oral mucositis (OM) remains a common, debilitating toxicity of radiation therapy (RT) for head and neck cancer. The goal of this phase IIb, multi-institutional, randomized, double-blind trial was to compare the efficacy and safety of GC4419, a superoxide dismutase mimetic, with placebo to reduce the duration, incidence, and severity of severe OM (SOM).
PATIENTS AND METHODS: A total of 223 patients (from 44 institutions) with locally advanced oral cavity or oropharynx cancer planned to be treated with definitive or postoperative intensity-modulated RT (IMRT; 60 to 72 Gy [≥ 50 Gy to two or more oral sites]) plus cisplatin (weekly or every 3 weeks) were randomly assigned to receive 30 mg (n = 73) or 90 mg (n = 76) of GC4419 or to receive placebo (n = 74) by 60-minute intravenous administration before each IMRT fraction. WHO grade of OM was assessed biweekly during IMRT and then weekly for up to 8 weeks after IMRT. The primary endpoint was duration of SOM tested for each active dose level versus placebo (intent-to-treat population, two-sided α of .05). The National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, was used for adverse event grading.
RESULTS: Baseline patient and tumor characteristics as well as treatment delivery were balanced. With 90 mg GC4419 versus placebo, SOM duration was significantly reduced (P = .024; median, 1.5 v 19 days). SOM incidence (43% v 65%; P = .009) and severity (grade 4 incidence, 16% v 30%; P = .045) also were improved. Intermediate improvements were seen with the 30-mg dose. Safety was comparable across arms, with no significant GC4419-specific toxicity nor increase of known toxicities of IMRT plus cisplatin. The 2-year follow-up for tumor outcomes is ongoing.
CONCLUSION: GC4419 at a dose of 90 mg produced a significant, clinically meaningful reduction of SOM duration, incidence, and severity with acceptable safety. A phase III trial (ROMAN; ClinicalTrials.gov identifier: NCT03689712) has begun.
Recommended Citation
Anderson, Carryn M.; Lee, Christopher M; Saunders, Deborah P.; Curtis, Amarinthia; Dunlap, Neal; Nangia, Chaitali; Lee, Arielle S.; Gordon, Sharon M.; Kovoor, Philip; Arevalo-Araujo, Roberto; Bar-Ad, Voichita; Peddada, Abhinand; Colvett, Kyle; Miller, Douglas; Jain, Anshu K.; Wheeler, James; Blakaj, Dukagjin; Bonomi, Marcelo; Agarwala, Sanjiv S.; Garg, Madhur; Worden, Francis; Holmlund, Jon; Brill, Jeffrey M.; Downs, Matt; Sonis, Stephen T.; Katz, Sanford; and Buatti, John M., "Phase IIb, Randomized, Double-Blind Trial of GC4419 Versus Placebo to Reduce Severe Oral Mucositis Due to Concurrent Radiotherapy and Cisplatin For Head and Neck Cancer." (2019). Department of Radiation Oncology Faculty Papers. Paper 126.
https://jdc.jefferson.edu/radoncfp/126
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
PubMed ID
31618127
Language
English
Comments
This article is the author’s final published version in Journal of Clinical Oncology, Volume 37, Issue 34, December 2019, Pages 3256-3265.
The published version is available at https://doi.org/10.1200/JCO.19.01507. Copyright © Anderson et al.