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
Author
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; Buatti, John M.
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.
Date
2019-12-01
Citation:
APA:
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, & Buatti, John M.. (December 2019).
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.
,
(),
-
. Retrieved from
http://hdl.handle.net/10342/8263
MLA:
Anderson, Carryn M., and Lee, Christopher M., and Saunders, Deborah P., and Curtis, Amarinthia, and Dunlap, Neal, and Nangia, Chaitali, and Lee, Arielle S., and Gordon, Sharon M., and Kovoor, Philip, and Arevalo-Araujo, Roberto, and Bar-Ad, Voichita, and Peddada, Abhinand, and Colvett, Kyle, and Miller, Douglas, and Jain, Anshu K., and Wheeler, James, and Blakaj, Dukagjin, and Bonomi, Marcelo, and Agarwala, Sanjiv S., and Garg, Madhur, and Worden, Francis, and Holmlund, Jon, and Brill, Jeffrey M., and Downs, Matt, and Sonis, Stephen T., and 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". .
. (),
December 2019.
May 17, 2024.
http://hdl.handle.net/10342/8263.
Chicago:
Anderson, Carryn M. and Lee, Christopher M. and Saunders, Deborah P. and Curtis, Amarinthia and Dunlap, Neal and Nangia, Chaitali and Lee, Arielle S. and Gordon, Sharon M. and Kovoor, Philip and Arevalo-Araujo, Roberto and Bar-Ad, Voichita and Peddada, Abhinand and Colvett, Kyle and Miller, Douglas and Jain, Anshu K. and Wheeler, James and Blakaj, Dukagjin and Bonomi, Marcelo and Agarwala, Sanjiv S. and Garg, Madhur and Worden, Francis and Holmlund, Jon and Brill, Jeffrey M. and Downs, Matt and Sonis, Stephen T. and 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," , no.
(December 2019),
http://hdl.handle.net/10342/8263 (accessed
May 17, 2024).
AMA:
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, 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. .
December 2019;
():
.
http://hdl.handle.net/10342/8263. Accessed
May 17, 2024.
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