Frontiers in Anti-Cancer Drug Discovery

Volume: 1

Older and New Formulations of Cladribine: Pharmacology and Clinical Efficacy in Hematological Malignancies

Author(s): Tadeusz Robak, Anna Korycka, Ewa Robak

Pp: 497-524 (28)

DOI: 10.2174/978160805161811001010497

* (Excluding Mailing and Handling)

Abstract

The purine nucleoside analog (PNA) - cladribine (2-CdA, 2-chlorodeoxyadenosine) is a cytotoxic agent of high efficacy in lymphoid and myeloid malignancies. This drug was approved by the FDA for treatment of hairy cell leukemia and in some European countries for treatment of refractory/relapsed chronic lymphocytic leukemia. 2-CdA is usually administered as continuous or intermittent intravenous infusion. Recently however, new formulations of this agent have been developed for subcutaneous and oral administration. In contrast to other PNA, 2-CdA is equally cytotoxic to both proliferating and quiescent cells and several pathways may be responsible for the mechanism of its action. In addition, recent data indicate that 2-CdA combined with other cytotoxic agents and monoclonal antibodies show synergistic proapoptotic and cytotoxic activity on lymphoid and myeloid neoplastic cells. This review article summarizes recent achievements in the understanding of 2-CdA mechanism of action, pharmacokinetics of different pharmaceutical formulations and its approved and possible future applications in the treatment of hematological malignancies.

The most important recent patents concerning oral formulations of 2-CdA have been presented.


Keywords: Cladribine, oral, subcutaneous, pharmacokinetics, leukemia, lymphoma, systemic mastocytosis, Langerhans cell histiocytosis, acute myeloid leukemia

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      • 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 <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1739834824 and j.to_date >= 1739834824 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 1783) 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 <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1739834824 and j.to_date >= 1739834824 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 1783) 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 <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1739834824 and j.to_date >= 1739834824 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 1783)
      580μsalphaeurekaselec_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` = 919 and `b`.`banner_from_date` <= 1739834824 and `b`.`banner_to_date` >= 1739834824 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.06msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 919
      • 3: 1739834824
      • 4: 1739834824
      • 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='5735bcf8085db1a8c3666e645f72668c'
      230μsalphaeurekaselec_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
    9Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        cFyY1ptoTRTn6ugovaPXjsaHiTYFuA7yzDRvlGi9
        uc_cart_id
        5735bcf8085db1a8c3666e645f72668c
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/1783" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/1783
        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:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6IjV0bHN2dEtkTHM1ZVpWQm55Rko3TVE9PSIsInZhbHVlIjoiR2JqRjdwMWZ1ZjNYV0JMbzU4Qmk1SzRhcUEyRTN4MlZ6SG9tUGc0RUlTST0iLCJtYWMiOiIwYjJiMTc1NmFkN2UyZTM5ZDZlMmYwOGM4NmRmZDI2ODkwZGNlMzU1MWI2YTRmZjU5MzE2NGQyYjJlZDMwMDg3IiwidGFnIjoiIn0%3D; XSRF-TOKEN=eyJpdiI6ImVMdjU4VU9tcm5yZ2pjVmtTb2J4U0E9PSIsInZhbHVlIjoiUzFJZXAvQkJLNlVXVlU4NTNoNE1mTmhDU2M5VlU3TWtZZU92Ym1QYjJWS2d1N1dmV0tBSjdVMXFYL2Y1V2l6eDNlaXVXV0l3N3VDMk9IN2ZZeklqVktWY1FNOXhYNmFqRmp6Rjlwamk0M1hmWm5Bcm41VVhCKzNlTGVNVTVvamMiLCJtYWMiOiIyYTA5YmY2ZTE3ODQyZGQzZmI4ODQxZjNmMjM2NzgwM2UwOWYwZDY4ODhjZjA3MGQ2MDY5Yjc0ODAzZDY0MTg1IiwidGFnIjoiIn0%3D; alphaeurekaselectnet_session=eyJpdiI6IlgrcnhmZ3IzNnppVVhNUFZWVUJxYXc9PSIsInZhbHVlIjoiZ0RkMWJXNTY3dmsxcDFBREVYLzBsTHQ4L3gvT25tdlFoTC83YXJqSkJMbkVCUXdwN0JoQ05HaFlBS2JzL2xuVW1BdVVlTzFGSnE3NGhYZnUzenNrSW5ZbHhaY2lZUVhRWExRNzMvdnNINW1PQy94ckN3cGJhUXE1OFNFVDVxUW8iLCJtYWMiOiJkMTgxNmNhNGMwNDBlMDU4MjBmNzJmZWZmOTI1ZTFjNzJhMjA0MjA5YzBiNTEyMDczM2E5Mzc1NTljMTViZWY1IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6IjV0bHN2dEtkTHM1ZVpWQm55Rko3TVE9PSIsInZhbHVlIjoiR2JqRjdwMWZ1ZjNYV0JMbzU4Qmk1SzRhcUEyRTN4MlZ6SG9tUGc0RUlTST0iLCJtYWMiOiIwYjJiMTc1NmFkN2Uy" ] "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
        0 of 0
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        response_headers
        0 of 0
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        session_attributes
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        array:5 [ "_token" => "cFyY1ptoTRTn6ugovaPXjsaHiTYFuA7yzDRvlGi9" "uc_cart_id" => "5735bcf8085db1a8c3666e645f72668c" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/1783" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-17 23:27:04GET/chapter/17831121911