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Safety, pharmacokinetics and efficacy findings in an open-label, single-arm study of weekly paclitaxel plus lapatinib as first-line therapy for Japanese women with HER2-positive metastatic breast cancer

BACKGROUND: Lapatinib is the human epidermal growth factor receptor 2 (HER2) targeting agent approved globally for HER2-positive metastatic breast cancer (MBC). The efficacy, safety and pharmacokinetics (PK) of lapatinib combined with paclitaxel (L+P) were investigated in this study, to establish cl...

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Autores principales: Inoue, Kenichi, Kuroi, Katsumasa, Shimizu, Satoru, Rai, Yoshiaki, Aogi, Kenjiro, Masuda, Norikazu, Nakayama, Takahiro, Iwata, Hiroji, Nishimura, Yuichiro, Armour, Alison, Sasaki, Yasutsuna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Japan 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666271/
https://www.ncbi.nlm.nih.gov/pubmed/25967286
http://dx.doi.org/10.1007/s10147-015-0832-5
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author Inoue, Kenichi
Kuroi, Katsumasa
Shimizu, Satoru
Rai, Yoshiaki
Aogi, Kenjiro
Masuda, Norikazu
Nakayama, Takahiro
Iwata, Hiroji
Nishimura, Yuichiro
Armour, Alison
Sasaki, Yasutsuna
author_facet Inoue, Kenichi
Kuroi, Katsumasa
Shimizu, Satoru
Rai, Yoshiaki
Aogi, Kenjiro
Masuda, Norikazu
Nakayama, Takahiro
Iwata, Hiroji
Nishimura, Yuichiro
Armour, Alison
Sasaki, Yasutsuna
author_sort Inoue, Kenichi
collection PubMed
description BACKGROUND: Lapatinib is the human epidermal growth factor receptor 2 (HER2) targeting agent approved globally for HER2-positive metastatic breast cancer (MBC). The efficacy, safety and pharmacokinetics (PK) of lapatinib combined with paclitaxel (L+P) were investigated in this study, to establish clear evidence regarding the combination in Japanese patients. METHODS: In this two-part, single-arm, open-label study, the tolerability of L+P as first-line treatment in Japanese patients with HER2-positive MBC was evaluated in six patients in the first part, and the safety, efficacy and PK were evaluated in a further six patients (making a total of twelve patients) in the second part. Eligible women were enrolled and received lapatinib 1500 mg once daily and paclitaxel 80 mg/m(2) weekly for at least 6 cycles. RESULTS: The only dose-limiting toxicity reported was Grade 3 diarrhea in one patient. The systemic exposure to maximum plasma concentration and area under the plasma concentration curve (AUC) for lapatinib, as well as the AUC of paclitaxel, were increased when combined. The most common adverse events (AEs) related to the study treatment were alopecia, diarrhea and decreased hemoglobin. The majority of drug-related AEs were Grade 1 or 2. The median overall survival was 35.6 months (95 % confidence interval 23.9, not reached). The response rate and clinical benefit rate were both 83 % (95 % confidence interval 51.6, 97.9). CONCLUSIONS: The L+P treatment was well tolerated in Japanese patients with HER2-positive MBC. Although the PK profiles of lapatinib and paclitaxel influenced each other, the magnitudes were not greatly different from those in non-Japanese patients.
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spelling pubmed-46662712015-12-09 Safety, pharmacokinetics and efficacy findings in an open-label, single-arm study of weekly paclitaxel plus lapatinib as first-line therapy for Japanese women with HER2-positive metastatic breast cancer Inoue, Kenichi Kuroi, Katsumasa Shimizu, Satoru Rai, Yoshiaki Aogi, Kenjiro Masuda, Norikazu Nakayama, Takahiro Iwata, Hiroji Nishimura, Yuichiro Armour, Alison Sasaki, Yasutsuna Int J Clin Oncol Original Article BACKGROUND: Lapatinib is the human epidermal growth factor receptor 2 (HER2) targeting agent approved globally for HER2-positive metastatic breast cancer (MBC). The efficacy, safety and pharmacokinetics (PK) of lapatinib combined with paclitaxel (L+P) were investigated in this study, to establish clear evidence regarding the combination in Japanese patients. METHODS: In this two-part, single-arm, open-label study, the tolerability of L+P as first-line treatment in Japanese patients with HER2-positive MBC was evaluated in six patients in the first part, and the safety, efficacy and PK were evaluated in a further six patients (making a total of twelve patients) in the second part. Eligible women were enrolled and received lapatinib 1500 mg once daily and paclitaxel 80 mg/m(2) weekly for at least 6 cycles. RESULTS: The only dose-limiting toxicity reported was Grade 3 diarrhea in one patient. The systemic exposure to maximum plasma concentration and area under the plasma concentration curve (AUC) for lapatinib, as well as the AUC of paclitaxel, were increased when combined. The most common adverse events (AEs) related to the study treatment were alopecia, diarrhea and decreased hemoglobin. The majority of drug-related AEs were Grade 1 or 2. The median overall survival was 35.6 months (95 % confidence interval 23.9, not reached). The response rate and clinical benefit rate were both 83 % (95 % confidence interval 51.6, 97.9). CONCLUSIONS: The L+P treatment was well tolerated in Japanese patients with HER2-positive MBC. Although the PK profiles of lapatinib and paclitaxel influenced each other, the magnitudes were not greatly different from those in non-Japanese patients. Springer Japan 2015-05-13 2015 /pmc/articles/PMC4666271/ /pubmed/25967286 http://dx.doi.org/10.1007/s10147-015-0832-5 Text en © The Author(s) 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Inoue, Kenichi
Kuroi, Katsumasa
Shimizu, Satoru
Rai, Yoshiaki
Aogi, Kenjiro
Masuda, Norikazu
Nakayama, Takahiro
Iwata, Hiroji
Nishimura, Yuichiro
Armour, Alison
Sasaki, Yasutsuna
Safety, pharmacokinetics and efficacy findings in an open-label, single-arm study of weekly paclitaxel plus lapatinib as first-line therapy for Japanese women with HER2-positive metastatic breast cancer
title Safety, pharmacokinetics and efficacy findings in an open-label, single-arm study of weekly paclitaxel plus lapatinib as first-line therapy for Japanese women with HER2-positive metastatic breast cancer
title_full Safety, pharmacokinetics and efficacy findings in an open-label, single-arm study of weekly paclitaxel plus lapatinib as first-line therapy for Japanese women with HER2-positive metastatic breast cancer
title_fullStr Safety, pharmacokinetics and efficacy findings in an open-label, single-arm study of weekly paclitaxel plus lapatinib as first-line therapy for Japanese women with HER2-positive metastatic breast cancer
title_full_unstemmed Safety, pharmacokinetics and efficacy findings in an open-label, single-arm study of weekly paclitaxel plus lapatinib as first-line therapy for Japanese women with HER2-positive metastatic breast cancer
title_short Safety, pharmacokinetics and efficacy findings in an open-label, single-arm study of weekly paclitaxel plus lapatinib as first-line therapy for Japanese women with HER2-positive metastatic breast cancer
title_sort safety, pharmacokinetics and efficacy findings in an open-label, single-arm study of weekly paclitaxel plus lapatinib as first-line therapy for japanese women with her2-positive metastatic breast cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666271/
https://www.ncbi.nlm.nih.gov/pubmed/25967286
http://dx.doi.org/10.1007/s10147-015-0832-5
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