Author(s): Dominique Leveque, Luc Gigou and Jean Pierre Bergerat
Page: [51 - 55] Pages: 5
* (Excluding Mailing and Handling)
Trastuzumab is a monoclonal antibody that targets the extracellular domain of HER2, a member of the epidermal growth factor receptor (EGFR) family. Trastuzumab is currently approved for the treatment of breast cancer overexpressing HER2, given alone or in combination with paclitaxel or docetaxel. Trastuzumab pharmacokinetics are characterized by a low systemic clearance, a low volume of distribution (4l) and a very long half-life (28 days) comparable to that of endogenous immunoglobulins G. The elimination pathways are not yet defined and the clinical relevance of trastuzumab kinetic variability is unknown. Whether exposure might correlate with toxic effects or inadequate response has not been explored. No drug-drug interactions have been reported. This is not surprising because based on the current knowledge, no monoclonal antibody (including trastuzumab) has been found to interact with major molecular pharmacokinetic determinants such enzymes, drug transporters or orphan nuclear receptors. Dosage regimens of trastuzumab are similar either it is used in the adjuvant setting (postoperative) or in metastatic disease. According to the official labelling, trastuzumab is given by intravenous perfusion at a dose based on body weight, weekly (metastatic, adjuvant) or 3-weekly (adjuvant). The schedule also includes a loading dose at the initiation of the treatment. The recommended duration of treatment is currently one year (adjuvant) or until the progression of the disease (metastatic). Regarding the adjuvant setting, different dosage regimens have been tested (from 9 weeks to 2 years) but the optimal duration of treatment is unknown. The short course of trastuzumab (9 weeks) appears promising in terms of activity, tolerance and cost but should be compared to 1 or 2-years treatments. In addition, dosing regimens might be optimized by integrating pharmacokinetic elements. In the adjuvant setting, given the more favorable kinetic situation (absence of tumor penetration), a less intense dosage regimen might be appropriate when compared with that used in metastatic disease. Further body weight is weakly related to trastuzumab exposure and it is not proven that it significantly affects clinical activity. These pharmacokinetic considerations may support the use of fixed doses given monthly, on short periods, for the treatment of early breast cancer.
Keywords: Trastuzumab, breast cancer, pharmacokinetics, dosage regimen
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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,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59852242 and j.to_ip >=59852242 )) and ((j.from_date <= 1736967750 and j.to_date >= 1736967750 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 11120)
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select * from `article` where `first_page` < '51' and is_uploaded = 1 and issue_id = 2186 order by cast(first_page as SIGNED) desc limit 1
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select * from `article` where `last_page` > '55' and is_uploaded = 1 and issue_id = 2186 order by cast(first_page as SIGNED) asc limit 1
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select `language_id` from `multilanguage` where `short_code` = 'en'
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select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
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select `id` from `multilanguage_article` where `article_id` = 11120 limit 1
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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` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 12 and `b`.`banner_from_date` <= 1736967750 and `b`.`banner_to_date` >= 1736967750 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
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select count(*) as aggregate from `uc_cart_products` where cart_id='fd3e609ef245362181ea0ad19eed2b4c'
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|
200
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