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Protective Agent Dramatically Cuts Post-Radiation Mucositis

By MedImaging International staff writers
Posted on 26 Sep 2018

A novel agent could dramatically reduce the incidence of severe oral mucositis in patients with head and neck cancer undergoing radiation therapy (RT), according to a new study.

Researchers at the University of Iowa (Iowa City, USA), Galera Therapeutics (Malvern, PA, USA), and other institutions conducted a study to determine whether GC4419, a superoxide dismutase mimetic (SDM) that converts superoxide to molecular oxygen (O2) and hydrogen peroxide (H2O2), could reduce the incidence, duration, and severity of radiation-induced oral mucositis. The study included 223 patients undergoing intensity modulated radiation therapy (IMRT) for locally advanced, non-metastatic squamous cell carcinoma of the head and neck, limited to the oral cavity or the oropharynx.

The patients were divided into three treatment groups; Group A received 30 mg of GC4419 per day, concurrent with daily fractions of IMRT, for a total of 60-72 Gy over approximately seven weeks, plus cisplatin administered at 80-100 mg/m2 once every three weeks, or 30-40 mg/m2 once weekly for six to seven doses. Group B received 90 mg GC4419 per day with the same protocol; and Group C received placebo daily, again with the same protocol.

The results revealed that GC4419 reduced the duration of severe radiation-induced oral mucositis by 92%. When analyzed by group, the median number of days of severe oral mucositis (grade 3 or 4) was 19 days for patients who received placebo, eight days for those who received 30 mg, and just 1.5 days for those receiving 90 mg. Beyond suffering from severe oral mucositis, the placebo group also required insertion of a gastrostomy tube for feeding. The study was presented at the American Chemical Society (ACS) annual meeting, held during August 2018 in Boston (MA, USA).

“Roughly 50% of all solid tumors are treated with radiation therapy. It has many beneficial effects, but a major side effect is inflammation, and normal tissue toxicity is the key limitation to tumor targeting,” said senior study co-author Dennis Riley, PhD, chief science officer at Galera Therapeutics. “Hydrogen peroxide is very toxic to cancer cells, so in a way we shifted the paradigm. We remove superoxide, which is toxic to normal cells, and convert it to hydrogen peroxide, which is toxic to cancer cells. So we believe we can transform radiotherapy and treatment of solid tumors.”

During RT, inflammation develops because the radiation breaks the oxygen-hydrogen (OH) bonds of water in the body, creating superoxide, which is toxic at high concentrations. Consequently, nearly all organisms living in the presence of oxygen contain SOD superoxide-scavenging enzymes. SOD has powerful antinflammatory activity, as it decreases reactive oxygen species (ROS) and oxidative stress, and thus inhibits endothelial activation.

Related Links:
University of Iowa
Galera Therapeutics

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68 (63.896179199219): SELECT fid FROM jos_deeppockets WHERE id=294775029 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294775029 AND published='1' LIMIT 1

69 (45.061111450195): SELECT id,name,sponsor_text FROM jos_deeppockets dp left outer join jos_channel_sponsor cs on dp.id=cs.fid WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id=213 ORDER BY `ordering`

70 (407.21893310547): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294775029 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

71 (383.13865661621): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294775029 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

72 (59.843063354492): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`

73 (81.062316894531): SELECT show_live FROM jos_com_show_setting LIMIT 1

74 (54.121017456055): SELECT show_live FROM jos_com_show_setting LIMIT 1

75 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1

76 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

77 (42.915344238281): SELECT show_live FROM jos_com_show_setting LIMIT 1

78 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1

79 (72.002410888672): SELECT show_live FROM jos_com_show_setting LIMIT 1

80 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1

81 (40.054321289062): SELECT show_live FROM jos_com_show_setting LIMIT 1

82 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

83 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1

84 (32.901763916016): SELECT show_live FROM jos_com_show_setting LIMIT 1

85 (34.809112548828): SELECT show_live FROM jos_com_show_setting LIMIT 1

86 (34.093856811523): SELECT show_live FROM jos_com_show_setting LIMIT 1

87 (72.002410888672): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294775029 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

88 (40.054321289062): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294775029 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

89 (44.107437133789): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`

90 (79.870223999023): SELECT show_live FROM jos_com_show_setting LIMIT 1

91 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1

92 (39.815902709961): SELECT show_live FROM jos_com_show_setting LIMIT 1

93 (38.14697265625): SELECT show_live FROM jos_com_show_setting LIMIT 1

94 (37.908554077148): SELECT show_live FROM jos_com_show_setting LIMIT 1

95 (39.100646972656): SELECT show_live FROM jos_com_show_setting LIMIT 1

96 (49.114227294922): SELECT show_live FROM jos_com_show_setting LIMIT 1

97 (37.908554077148): SELECT show_live FROM jos_com_show_setting LIMIT 1

98 (37.908554077148): SELECT show_live FROM jos_com_show_setting LIMIT 1

99 (38.14697265625): SELECT show_live FROM jos_com_show_setting LIMIT 1

100 (42.915344238281): SELECT show_live FROM jos_com_show_setting LIMIT 1

101 (43.153762817383): SELECT show_live FROM jos_com_show_setting LIMIT 1

102 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1

103 (43.869018554688): SELECT show_live FROM jos_com_show_setting LIMIT 1

104 (110.86463928223): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

105 (91.075897216797): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

106 (99.897384643555): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294775029 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

107 (67.949295043945): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294775029 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

108 (92.983245849609): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

109 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

110 (80.108642578125): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294775029 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

111 (693.79806518555): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294775029 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

112 (787.01972961426): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1

113 (628.94821166992): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1

114 (200.03318786621): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

115 (93.936920166016): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

116 (90.837478637695): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

117 (66.995620727539): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

118 (130.89179992676): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

119 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

120 (387.19177246094): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`

121 (!!!!! 28883.934020996): SELECT * FROM jos_deeppockets WHERE jos_deeppockets.cat = 10 AND jos_deeppockets.type = 'deeppockets_item' AND jos_deeppockets.published = 1 AND jos_deeppockets.created + INTERVAL 14 DAY >= NOW() ORDER BY jos_deeppockets.hits DESC LIMIT 7

122 (181.91337585449): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

123 (73.909759521484): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

124 (669.00253295898): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294775029 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294775029 AND type='deeppockets_item' AND published='1' LIMIT 1

125 (!!!!! 686548.94828796): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3

126 (164.98565673828): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3

127 (64.13459777832): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294800513 LIMIT 1

128 (51.021575927734): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294800513 LIMIT 1

129 (72.956085205078): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294800359 LIMIT 1

130 (42.915344238281): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294800359 LIMIT 1

131 (156.16416931152): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294800361 LIMIT 1

132 (47.922134399414): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294800361 LIMIT 1

133 (756.02531433105): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

134 (582.93342590332): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

135 (312.08992004395): SELECT name FROM jos_deeppockets WHERE id=213

136 (46.968460083008): SELECT name FROM jos_deeppockets WHERE id=213

137 (648.02169799805): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))213((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

138 (586.03286743164): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))213((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

139 (98.943710327148): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

140 (74.148178100586): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

141 (!!!!! 11857.032775879): TRUNCATE TABLE jos_trademed_module

142 (124.21607971191): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294775029 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

143 (75.101852416992): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294775029 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

144 (!!!!! 1198.0533599854): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

145 (86.784362792969): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

146 (140.90538024902): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

147 (74.863433837891): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

148 (!!!!! 1626.9683837891): SELECT jos_item.* FROM jos_item INNER JOIN jos_number ON jos_item.numberID=jos_number.id WHERE 1=1 AND (jos_item.imgMini<>'') AND jos_item.type='L' AND jos_item.numberID= ( SELECT jos_number.id FROM jos_number WHERE jos_number.journalID IN (10) and jos_number.id in (select distinct jos_number.id from jos_number join jos_item on jos_item.numberid=jos_number.id where jos_item.type='P') ORDER BY (CONVERT(SUBSTRING(issue,1,2),SIGNED) + (CONVERT(SUBSTRING(issue,3,2),SIGNED)*100)) DESC LIMIT 0,1 ) ORDER BY RAND() DESC LIMIT 6

149 (100.13580322266): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

150 (68.902969360352): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

151 (59.127807617188): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294775029 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294775029 AND type='deeppockets_item' AND published='1' LIMIT 1

152 (67.949295043945): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=213 or channel_id is null)

153 (45.061111450195): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=213 or channel_id is null)

154 (54.836273193359): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1

155 (114.91775512695): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

156 (95.844268798828): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294775029 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294775029 AND published='1' LIMIT 1

157 (52.928924560547): select jos_twitters.link from jos_twitters where cat=10

158 (46.014785766602): select jos_facebook.link from jos_facebook where cat=10

159 (61.988830566406): select jos_google_plus.link from jos_google_plus where cat=10

160 (40.054321289062): select jos_linkedin.link from jos_linkedin where cat=10

161 (437.97492980957): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)

162 (!!!!! 1767.8737640381): insert into jos_banners_delta values (14615,'2025-04-30 07:32:36','3.146.206.0','view'),(14202,'2025-04-30 07:32:36','3.146.206.0','view'),(14203,'2025-04-30 07:32:36','3.146.206.0','view')

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