Frontiers in Drug Design and Discovery

Volume: 4

Important Drug Interactions for Clinical Oncologists

Author(s): Hiroshi Ishiguro, Ikuko Yano and Masakazu Toi

Pp: 97-121 (25)

DOI: 10.2174/978160805202810904010097

* (Excluding Mailing and Handling)

Abstract

Drug interactions can cause severe side effects and lead to early termination of drug development, refusal of drug approval, prescribing restrictions or drug withdrawal from the market. Of drugs used to treat humans, cytotoxic anti-neoplastic drugs have a particularly strong action. Furthermore, they have a complex pharmacological profile, a narrow therapeutic window, and a steep dose-toxicity curve, and are associated with considerable inter- and intrapatient pharmacokinetic and pharmacodynamic differences. The recommended dose is usually close to the maximally tolerated dose in order to achieve the maximum therapeutic effect. Thus, some adverse effects are usually inevitable, so these drugs are approved for usage based on a clinical risk to benefit ratio. Therefore, drug interactions affecting the pharmacokinetics of anti-neoplastic drugs are of particular concern. Any physicians treating oncology patients must understand the pharmacokinetic behavior (absorption, distribution, metabolism, excretion, etc.) of a drug, as well as the factors affecting its pharmacokinetic behavior, for example the effects of concomitantly administered drugs, and hepatic and renal function. Medical oncologists must have expertise in achieving a good balance between safety and efficacy in medical treatment, with a proper knowledge of supportive care and an understanding of pharmacokinetics, pharmacodynamics and pharmacogenomics. We summarize the drug interactions that are important in day-to-day oncology practice. We cover pharmaceutical interactions as well as the interactions at the levels of absorption, distribution, metabolism and excretion. This review is the one of the most comprehensive to date in the field of clinical oncology, where the level of understanding of drug interactions can directly affect patient management.

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      • 14. app/Http/Controllers/ChapterController.php:1518
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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 <= 59885649 and j.to_ip >=59885649 )) and ((j.from_date <= 1740515485 and j.to_date >= 1740515485 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 2204) 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 <= 59885649 and j.to_ip >=59885649 )) and ((j.from_date <= 1740515485 and j.to_date >= 1740515485 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 2204) 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 <= 59885649 and j.to_ip >=59885649 )) and ((j.from_date <= 1740515485 and j.to_date >= 1740515485 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 2204)
      530μsalphaeurekaselec_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` = 945 and `b`.`banner_from_date` <= 1740515486 and `b`.`banner_to_date` >= 1740515486 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.03msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 945
      • 3: 1740515486
      • 4: 1740515486
      • 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='8a36436cb926b7521332e0498e418ea9'
      180μsalphaeurekaselec_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\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        X4j5kxWDOAD9TiGUeRLWCFKf7TgL7H7R3im4AyFT
        uc_cart_id
        8a36436cb926b7521332e0498e418ea9
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/2204" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/2204
        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=eyJpdiI6IlBFK0ZucjlVV2lyZlhNTU52VmttYUE9PSIsInZhbHVlIjoiK2J0TTFOcFVBdUJabStnck5mWCtjeTlMaVN1bDJIc2YvUWd6MjRqcDVGaz0iLCJtYWMiOiIxM2RhMjJjY2U1ZWVjZmFkN2ViOTI4MmU0ZjNiNmMxYjVlYTZlYjZlMjdlZjU1OTE2MmE3YmJmYzMzOWE5YTgwIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6IlBFK0ZucjlVV2lyZlhNTU52VmttYUE9PSIsInZhbHVlIjoiK2J0TTFOcFVBdUJabStnck5mWCtjeTlMaVN1bDJIc2YvUWd6MjRqcDVGaz0iLCJtYWMiOiIxM2RhMjJjY2U1ZWVj" ] "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
        array:1 [ "wayfindertarget" => null ]
        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 20:31:26 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InB3YjNQeUJBRVdkd3cveStSWlBNRnc9PSIsInZhbHVlIjoiMjJ6eWhnR3h0Qm8vSVJSN0V3dHI2VTBrN1JSSTRhRFdpUHhOTFhNdHVMTlVySEhlcjBRWkdQYkh6UVVZZlhJdnV5QVc0cll3ZW0yUmJIV01uT3dXZXk4NFFnVVlGRGZ1RTBzb0JPd2VMbEs3NkJ1UWx1SFl4a0dkNCtjeFNtL0siLCJtYWMiOiI0YWQ4MTQ2ZmRkOTI0N2Q5YTczYzk0NmFmMzg1YWYxYzRkMDU4NjJmZTc4MTRhNTIwNTQxMDVhMjRkNjA2N2UzIiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 08:31:26 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6InB3YjNQeUJBRVdkd3cveStSWlBNRnc9PSIsInZhbHVlIjoiMjJ6eWhnR3h0Qm8vSVJSN0V3dHI2VTBrN1JSSTRhRFdpUHhOTFhNdHVMTlVySEhlcjBRWkdQYkh6UVVZZlhJdnV5QVc0c" 1 => "alphaeurekaselectnet_session=eyJpdiI6IllQL1FhRHZwWVUzYnE3ZnhZSG9LclE9PSIsInZhbHVlIjoiZVRDejJoRHY2dlF2bEhnUnFvaWpoWEVHTGVPMytUS1VMbncwamd3aEZQVmVOWUFYRTlLZmdWVGlJSThTenNRbTIxRDN1b3o1RTZCZk93dHFzK25RTDVPQmRNUW1YS2M3YkFISHdiMm9mN29QWWN0YUNOZFFwVGhkbzgyU3lYRjgiLCJtYWMiOiI3YmJlNzk4Y2U4Mzc0YTQyNjJiODQ4OTBhZTQyN2NmYjY0NDUyNjMwMjJiMGUxZWY1MzI1NzRlYzI1ZjY5YmUyIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IllQL1FhRHZwWVUzYnE3ZnhZSG9LclE9PSIsInZhbHVlIjoiZVRDejJoRHY2dlF2bEhnUnFvaWpoWEVHTGVPMytUS1VMbncwamd3aEZQVmVOWUFYRTlLZmdWVGl" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InB3YjNQeUJBRVdkd3cveStSWlBNRnc9PSIsInZhbHVlIjoiMjJ6eWhnR3h0Qm8vSVJSN0V3dHI2VTBrN1JSSTRhRFdpUHhOTFhNdHVMTlVySEhlcjBRWkdQYkh6UVVZZlhJdnV5QVc0cll3ZW0yUmJIV01uT3dXZXk4NFFnVVlGRGZ1RTBzb0JPd2VMbEs3NkJ1UWx1SFl4a0dkNCtjeFNtL0siLCJtYWMiOiI0YWQ4MTQ2ZmRkOTI0N2Q5YTczYzk0NmFmMzg1YWYxYzRkMDU4NjJmZTc4MTRhNTIwNTQxMDVhMjRkNjA2N2UzIiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 08:31:26 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6InB3YjNQeUJBRVdkd3cveStSWlBNRnc9PSIsInZhbHVlIjoiMjJ6eWhnR3h0Qm8vSVJSN0V3dHI2VTBrN1JSSTRhRFdpUHhOTFhNdHVMTlVySEhlcjBRWkdQYkh6UVVZZlhJdnV5QVc0c" 1 => "alphaeurekaselectnet_session=eyJpdiI6IllQL1FhRHZwWVUzYnE3ZnhZSG9LclE9PSIsInZhbHVlIjoiZVRDejJoRHY2dlF2bEhnUnFvaWpoWEVHTGVPMytUS1VMbncwamd3aEZQVmVOWUFYRTlLZmdWVGlJSThTenNRbTIxRDN1b3o1RTZCZk93dHFzK25RTDVPQmRNUW1YS2M3YkFISHdiMm9mN29QWWN0YUNOZFFwVGhkbzgyU3lYRjgiLCJtYWMiOiI3YmJlNzk4Y2U4Mzc0YTQyNjJiODQ4OTBhZTQyN2NmYjY0NDUyNjMwMjJiMGUxZWY1MzI1NzRlYzI1ZjY5YmUyIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IllQL1FhRHZwWVUzYnE3ZnhZSG9LclE9PSIsInZhbHVlIjoiZVRDejJoRHY2dlF2bEhnUnFvaWpoWEVHTGVPMytUS1VMbncwamd3aEZQVmVOWUFYRTlLZmdWVGl" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "X4j5kxWDOAD9TiGUeRLWCFKf7TgL7H7R3im4AyFT" "uc_cart_id" => "8a36436cb926b7521332e0498e418ea9" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/2204" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 20:31:26GET/chapter/2204112192