Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer
Background: Chemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX. Methods: We compared three different doses of q3w nab-...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-02-01
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| Series: | Breast |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0960977620302319 |
| _version_ | 1819160735925665792 |
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| author | Junji Tsurutani Fumikata Hara Masahiro Kitada Masato Takahashi Yuichiro Kikawa Hiroaki Kato Eiko Sakata Yoichi Naito Yoshie Hasegawa Tsuyoshi Saito Tsutomu Iwasa Naruto Taira Tsutomu Takashima Kosuke Kashiwabara Tomohiko Aihara Hirofumi Mukai |
| author_facet | Junji Tsurutani Fumikata Hara Masahiro Kitada Masato Takahashi Yuichiro Kikawa Hiroaki Kato Eiko Sakata Yoichi Naito Yoshie Hasegawa Tsuyoshi Saito Tsutomu Iwasa Naruto Taira Tsutomu Takashima Kosuke Kashiwabara Tomohiko Aihara Hirofumi Mukai |
| author_sort | Junji Tsurutani |
| collection | DOAJ |
| description | Background: Chemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX. Methods: We compared three different doses of q3w nab-PTX (Standard: 260 mg/m2 [SD260] vs Medium: 220 mg/m2 [MD220] vs Low: 180 mg/m2 [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was <0.75 or >1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded. Results: One hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42–1.28) in MD220 vs SD260, 0.77 (95% CI 0.47–1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56–1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180. Conclusions: Intravenous administration of low-dose nab-PTX at 180 mg/m2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC. |
| first_indexed | 2024-12-22T17:01:11Z |
| format | Article |
| id | doaj.art-47ae3af95d7143318f7fa81b47457151 |
| institution | Directory Open Access Journal |
| issn | 1532-3080 |
| language | English |
| last_indexed | 2024-12-22T17:01:11Z |
| publishDate | 2021-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Breast |
| spelling | doaj.art-47ae3af95d7143318f7fa81b474571512022-12-21T18:19:20ZengElsevierBreast1532-30802021-02-01556368Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancerJunji Tsurutani0Fumikata Hara1Masahiro Kitada2Masato Takahashi3Yuichiro Kikawa4Hiroaki Kato5Eiko Sakata6Yoichi Naito7Yoshie Hasegawa8Tsuyoshi Saito9Tsutomu Iwasa10Naruto Taira11Tsutomu Takashima12Kosuke Kashiwabara13Tomohiko Aihara14Hirofumi Mukai15Advanced Cancer Translational Research Institute, Showa University, Tokyo, Japan; Corresponding author.Department of Breast Medical Oncology, Cancer Institute Hospital of JFCR, Koto, Tokyo, JapanDepartment of Breast Disease Center, Asahikawa Medical University Hospital, Asahikawa, JapanNHO Hokkaido Cancer Center, Sapporo, JapanDepartment of Breast Surgery, Kobe City Medical Center General Hospital, Kobe, JapanTeine Keijinkai Hospital, Sapporo, JapanNiigata City General Hospital, Niigata, JapanDepartment of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, JapanDepartment of Breast Surgery, Hirosaki Municipal Hospital, Hirosaki, JapanJapanese Red Cross Saitama Hospital, Saitama, JapanDepartment of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, JapanOkayama University Hospital, Okayama, JapanOsaka City University Graduate School of Medicine, Osaka, JapanClinical Research Promotion Center, The University of Tokyo Hospital, Tokyo, JapanBreast Center, Aihara Hospital, Minoh, JapanNational Cancer Center Hospital East, Kashiwa, Chiba, JapanBackground: Chemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX. Methods: We compared three different doses of q3w nab-PTX (Standard: 260 mg/m2 [SD260] vs Medium: 220 mg/m2 [MD220] vs Low: 180 mg/m2 [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was <0.75 or >1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded. Results: One hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42–1.28) in MD220 vs SD260, 0.77 (95% CI 0.47–1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56–1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180. Conclusions: Intravenous administration of low-dose nab-PTX at 180 mg/m2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC.http://www.sciencedirect.com/science/article/pii/S0960977620302319Nab-paclitaxelNanoparticle albumin–bound paclitaxelMetastatic breast cancerSolvent-base paclitaxelChemotherapy-induced peripheral neuropathy |
| spellingShingle | Junji Tsurutani Fumikata Hara Masahiro Kitada Masato Takahashi Yuichiro Kikawa Hiroaki Kato Eiko Sakata Yoichi Naito Yoshie Hasegawa Tsuyoshi Saito Tsutomu Iwasa Naruto Taira Tsutomu Takashima Kosuke Kashiwabara Tomohiko Aihara Hirofumi Mukai Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer Breast Nab-paclitaxel Nanoparticle albumin–bound paclitaxel Metastatic breast cancer Solvent-base paclitaxel Chemotherapy-induced peripheral neuropathy |
| title | Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer |
| title_full | Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer |
| title_fullStr | Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer |
| title_full_unstemmed | Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer |
| title_short | Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer |
| title_sort | randomized phase ii study to determine the optimal dose of 3 week cycle nab paclitaxel in patients with metastatic breast cancer |
| topic | Nab-paclitaxel Nanoparticle albumin–bound paclitaxel Metastatic breast cancer Solvent-base paclitaxel Chemotherapy-induced peripheral neuropathy |
| url | http://www.sciencedirect.com/science/article/pii/S0960977620302319 |
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