Frontiers in Anti-Cancer Drug Discovery

Volume: 9

Dabrafenib in Melanoma

Author(s): Meredith McKean and Rodabe N. Amaria

Pp: 64-90 (27)

DOI: 10.2174/9781681087016118090004

* (Excluding Mailing and Handling)

Abstract

Approximately 40% of patients with cutaneous melanoma have an activating mutation in BRAF kinase, leading to constitutive activation of the mitogen-activated protein kinase pathway and unregulated cell growth. Selective inhibitors of the mutated BRAF kinase produce response rates of approximately 50%, median progression free survival of 6 to 7 months, and 5-year OS rate of 20% in patients with BRAF V600E/K mutant metastatic melanoma. BRAF blocking therapies work rapidly, with responses seen within 2 weeks after therapy initiation, and they are associated with generally mild toxicities. Most patients, however, develop resistance to BRAF inhibition. Dual inhibition of BRAF and MEK has demonstrated improved efficacy over single agent therapy with a median overall survival of 25.1 months and long-term follow-up showing 23% five-year overall survival rate. The FDA approved single agent therapy with BRAF inhibitor dabrafenib and in combination with MEK inhibitor trametinib for use in patients with BRAF V600 mutated metastatic melanoma in 2014. Now either targeted therapy or immune checkpoint inhibitors are selected for front-line treatment in the metastatic setting based on individual patient factors since there is no evidence to demonstrate a superior regimen. Sequencing of these agents is currently being explored in clinical trials. Studies are also ongoing to assess the benefit of targeted therapy with BRAF and MEK inhibitors in conjunction with immunotherapy. Additionally, oncogenic BRAF mutations have been identified in other solid tumors including papillary thyroid, colon, and non-small cell lung cancers. BRAF inhibition has been explored in these malignancies leading to FDA approval in non-small cell lung cancer and ongoing investigation of combination therapies. Methods: Pubmed and MESH databases were searched for literature published between 2010-2018 using the keywords of melanoma, dabrafenib, vemurafenib, trametinib, and BRAF.


Keywords: Adjuvant, BRAF Mutation, Central Nervous System, Dabrafenib, Immunotherapy, Ipilimumab, Keratoacanthoma, MEK Inhibition, Melanoma, Neoadjuvant, Nivolumab, Pembrolizumab, Resistance, Targeted Therapy, Trametinib, Vemurafenib.

Related Journals
Related Books
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version194msRequest Duration26MBMemory UsageGET chapter/{id}/{param?}Route
  • warninglog[20:36:19] LOG.warning: Optional parameter $id declared before required parameter $request is implic...
  • Booting (101ms)time
  • Application (93.15ms)time
  • 1 x Booting (52.08%)
    101ms
    1 x Application (47.92%)
    93.15ms
    12 templates were rendered
    • ebook.chapter_detailschapter_details.blade.php#?blade
    • layouts.chapter_header_sectionchapter_header_section.blade.php#?blade
    • ebook.chapter_top_bannerchapter_top_banner.blade.php#?blade
    • ebook.chapter_bottom_bannerchapter_bottom_banner.blade.php#?blade
    • ebook.ebook_right_bannerebook_right_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET chapter/{id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ChapterController@GetChapterDetails
    namespace
    App\Http\Controllers
    where
    as
    chapter
    file
    app/Http/Controllers/ChapterController.php:1350-1704
    19 statements were executed31.4ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('51718564','',1,1740515779,1740515779) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740515779
      1.15msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('51718564','/chapter/12783',1,1740515779,1740515779)
      870μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 51718564 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51718564) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 51718564 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51718564) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 51718564 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51718564) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 51718564 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51718564) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 51718564 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51718564) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 51718564 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51718564) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 51718564 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51718564) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 51718564 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51718564) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 51718564 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51718564) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 51718564 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51718564) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 51718564 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51718564) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 51718564 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51718564) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 51718564 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51718564) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 51718564 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51718564) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 51718564 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51718564) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 51718564 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51718564) limit 1
      20.2msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 51718564
      • 1: 51718564
      • 2: 51718564
      • 3: 51718564
      • 4: 51718564
      • 5: 51718564
      • 6: 51718564
      • 7: 51718564
      • 8: 51718564
      • 9: 51718564
      • 10: 51718564
      • 11: 51718564
      • 12: 51718564
      • 13: 51718564
      • 14: 51718564
      • 15: 51718564
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • select * from `chapter` where `chapter_id` = '12783' limit 1
      340μsalphaeurekaselec_live_10_06_2022ChapterController.php#1406
      Bindings
      • 0: 12783
      Backtrace
      • 16. app/Http/Controllers/ChapterController.php:1406
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`chapter_id` = '12783' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      1.11msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 12783
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ChapterController.php:1411
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `keywords` where `chapter_id` = '12783'
      340μsalphaeurekaselec_live_10_06_2022ChapterController.php#1415
      Bindings
      • 0: 12783
      Backtrace
      • 15. app/Http/Controllers/ChapterController.php:1415
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select * from `ebook` where `ebook_id` = 132 limit 1
      280μsalphaeurekaselec_live_10_06_2022ChapterController.php#1430
      Bindings
      • 0: 132
      Backtrace
      • 16. app/Http/Controllers/ChapterController.php:1430
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select count(*) as aggregate from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `e`.`ebook_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=132) and se.ebook_id!=132 and v.ebook_status='1'
      920μsalphaeurekaselec_live_10_06_2022Subject.php#238
      Backtrace
      • 16. app/Models/Subject.php:238
      • 17. app/Http/Controllers/ChapterController.php:1434
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 19. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select distinct v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `e`.`ebook_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=132) and se.ebook_id!=132 and v.ebook_status='1' limit 10 offset 0
      760μsalphaeurekaselec_live_10_06_2022Subject.php#238
      Backtrace
      • 14. app/Models/Subject.php:238
      • 15. app/Http/Controllers/ChapterController.php:1434
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as aggregate from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=132)
      450μsalphaeurekaselec_live_10_06_2022Subject.php#255
      Backtrace
      • 16. app/Models/Subject.php:255
      • 17. app/Http/Controllers/ChapterController.php:1435
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 19. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select distinct j.nid as journal_nid,j.title,j.subtitle,j.issn,j.eissn,j.keyword,sj.journal_id,j.image_file_name,j.flyer_link from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=132) limit 10 offset 0
      470μsalphaeurekaselec_live_10_06_2022Subject.php#255
      Backtrace
      • 14. app/Models/Subject.php:255
      • 15. app/Http/Controllers/ChapterController.php:1435
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `e`.*, `a`.*, `y`.`year`, `e`.`ebook_volume_id` as `ebook_volume_id`, `a`.`ebook_volume_id` as `ebk_vol_id`, `e`.`ebook_id` as `ebk_ebook_id` from `ebook_volume` as `e` left join `author` as `a` on `e`.`ebook_volume_id` = `a`.`ebook_volume_id` left join `year` as `y` on `y`.`id` = `e`.`year_id` where `e`.`ebook_volume_id` = 2632 and `e`.`is_uploaded` = 1
      550μsalphaeurekaselec_live_10_06_2022EbookVolume.php#271
      Bindings
      • 0: 2632
      • 1: 1
      Backtrace
      • 13. app/Models/EbookVolume.php:271
      • 14. app/Http/Controllers/ChapterController.php:1438
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) rcd from `ebook_volume` where `ebook_id` = 132 and ebook_volume_id <> 2632 limit 1
      300μsalphaeurekaselec_live_10_06_2022EbookVolume.php#999
      Bindings
      • 0: 132
      Backtrace
      • 14. app/Models/EbookVolume.php:999
      • 15. app/Http/Controllers/ChapterController.php:1462
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from ebook_access where content_type_id = '12783' and content_type = 'c' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      360μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1465
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from ebook_access where content_type_id = '2632' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      320μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1478
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"ebook_volume" as access_level,"" as chapter_id from `user_access_ebook_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51718564 and j.to_ip >=51718564 )) and ((j.from_date <= 1740515779 and j.to_date >= 1740515779 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2632) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"ebook_volume" as access_level,"" as chapter_id from `user_access_ebook_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51718564 and j.to_ip >=51718564 )) and ((j.from_date <= 1740515779 and j.to_date >= 1740515779 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2632) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"ebook_volume" as access_level,"" as chapter_id from `user_access_ebook_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51718564 and j.to_ip >=51718564 )) and ((j.from_date <= 1740515779 and j.to_date >= 1740515779 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2632)
      660μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51718564 and j.to_ip >=51718564 )) and ((j.from_date <= 1740515779 and j.to_date >= 1740515779 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12783) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51718564 and j.to_ip >=51718564 )) and ((j.from_date <= 1740515779 and j.to_date >= 1740515779 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12783) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51718564 and j.to_ip >=51718564 )) and ((j.from_date <= 1740515779 and j.to_date >= 1740515779 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12783)
      620μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 2632 and `b`.`banner_from_date` <= 1740515779 and `b`.`banner_to_date` >= 1740515779 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.45msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 2632
      • 3: 1740515779
      • 4: 1740515779
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='24041e77cb21e16eab53123ff24e19fa'
      250μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    16Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        ZBs8mPIRhCazz7SAnO68nS13fKQso4KjhvywE7xc
        uc_cart_id
        24041e77cb21e16eab53123ff24e19fa
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/12783" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/12783
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:16 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 20:36:19 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InNjVzdHaE1WSFZaUk4wY2JkRCtpRFE9PSIsInZhbHVlIjoiMlpMMXo4S0x3UTArd0pPOGRMeG5lL2NQTVd2b1Npazl2L0JkU3RyRVRKajVSRFE4Mi9PanZIbHV6aUFCYmRQK25DckVhY005aklFTU5ORXZMM3hNZ0pLYjc2VDFaWEU3SkM2eFNLUHJ2Y1BaQjZnS2lmNjQyOG9CZnJxZndKb3AiLCJtYWMiOiI4MmMxZTExMDAyNzc3OTMyYTEyYzJjZTdiYmU5Mzg1MTVjODMxMDBlNWQ1M2IzN2VhNDM1YjI2N2FjNzRjYWQ5IiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 08:36:19 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6InNjVzdHaE1WSFZaUk4wY2JkRCtpRFE9PSIsInZhbHVlIjoiMlpMMXo4S0x3UTArd0pPOGRMeG5lL2NQTVd2b1Npazl2L0JkU3RyRVRKajVSRFE4Mi9PanZIbHV6aUFCYmRQK25DckVhY" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkVxWDhhSkVyaDBhc1hvUjVWMi85Unc9PSIsInZhbHVlIjoiVS9FYStSSFdLTHBsT043WEZybVNIWnZ2WGRoY3dLak1Xc2syM0V4UGUzaDNKRlBBNmJoSWo4T3FNWHFBVXpSK0kwTTczOXEveWRMTHFOL2ZkUThnemNpT0lMb3lVdUMyU3RJSm9wZlB3QVV0ZnVDdlJGQkpvU0p2V3ZoZHJKR0QiLCJtYWMiOiJhYzljYmI5MGI4NzI0YWNmMDJmZjA3MTllMjU4ZDZlZGQ2OWEyYTIxYWI0ZGNjYjZiODMzOTJiNjYwZGNhNjEwIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IkVxWDhhSkVyaDBhc1hvUjVWMi85Unc9PSIsInZhbHVlIjoiVS9FYStSSFdLTHBsT043WEZybVNIWnZ2WGRoY3dLak1Xc2syM0V4UGUzaDNKRlBBNmJoSWo4T3F" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InNjVzdHaE1WSFZaUk4wY2JkRCtpRFE9PSIsInZhbHVlIjoiMlpMMXo4S0x3UTArd0pPOGRMeG5lL2NQTVd2b1Npazl2L0JkU3RyRVRKajVSRFE4Mi9PanZIbHV6aUFCYmRQK25DckVhY005aklFTU5ORXZMM3hNZ0pLYjc2VDFaWEU3SkM2eFNLUHJ2Y1BaQjZnS2lmNjQyOG9CZnJxZndKb3AiLCJtYWMiOiI4MmMxZTExMDAyNzc3OTMyYTEyYzJjZTdiYmU5Mzg1MTVjODMxMDBlNWQ1M2IzN2VhNDM1YjI2N2FjNzRjYWQ5IiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 08:36:19 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6InNjVzdHaE1WSFZaUk4wY2JkRCtpRFE9PSIsInZhbHVlIjoiMlpMMXo4S0x3UTArd0pPOGRMeG5lL2NQTVd2b1Npazl2L0JkU3RyRVRKajVSRFE4Mi9PanZIbHV6aUFCYmRQK25DckVhY" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkVxWDhhSkVyaDBhc1hvUjVWMi85Unc9PSIsInZhbHVlIjoiVS9FYStSSFdLTHBsT043WEZybVNIWnZ2WGRoY3dLak1Xc2syM0V4UGUzaDNKRlBBNmJoSWo4T3FNWHFBVXpSK0kwTTczOXEveWRMTHFOL2ZkUThnemNpT0lMb3lVdUMyU3RJSm9wZlB3QVV0ZnVDdlJGQkpvU0p2V3ZoZHJKR0QiLCJtYWMiOiJhYzljYmI5MGI4NzI0YWNmMDJmZjA3MTllMjU4ZDZlZGQ2OWEyYTIxYWI0ZGNjYjZiODMzOTJiNjYwZGNhNjEwIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IkVxWDhhSkVyaDBhc1hvUjVWMi85Unc9PSIsInZhbHVlIjoiVS9FYStSSFdLTHBsT043WEZybVNIWnZ2WGRoY3dLak1Xc2syM0V4UGUzaDNKRlBBNmJoSWo4T3F" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "ZBs8mPIRhCazz7SAnO68nS13fKQso4KjhvywE7xc" "uc_cart_id" => "24041e77cb21e16eab53123ff24e19fa" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/12783" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 20:36:19GET/chapter/127831121918