Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer.

Autor: Tsurutani J; Advanced Cancer Translational Research Institute, Showa University, Tokyo, Japan. Electronic address: tsurutaj@med.showa-u.ac.jp., Hara F; Department of Breast Medical Oncology, Cancer Institute Hospital of JFCR, Koto, Tokyo, Japan., Kitada M; Department of Breast Disease Center, Asahikawa Medical University Hospital, Asahikawa, Japan., Takahashi M; NHO Hokkaido Cancer Center, Sapporo, Japan., Kikawa Y; Department of Breast Surgery, Kobe City Medical Center General Hospital, Kobe, Japan., Kato H; Teine Keijinkai Hospital, Sapporo, Japan., Sakata E; Niigata City General Hospital, Niigata, Japan., Naito Y; Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Hasegawa Y; Department of Breast Surgery, Hirosaki Municipal Hospital, Hirosaki, Japan., Saito T; Japanese Red Cross Saitama Hospital, Saitama, Japan., Iwasa T; Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan., Taira N; Okayama University Hospital, Okayama, Japan., Takashima T; Osaka City University Graduate School of Medicine, Osaka, Japan., Kashiwabara K; Clinical Research Promotion Center, The University of Tokyo Hospital, Tokyo, Japan., Aihara T; Breast Center, Aihara Hospital, Minoh, Japan., Mukai H; National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Jazyk: angličtina
Zdroj: Breast (Edinburgh, Scotland) [Breast] 2021 Feb; Vol. 55, pp. 63-68. Date of Electronic Publication: 2020 Dec 09.
DOI: 10.1016/j.breast.2020.12.002
Abstrakt: 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/m 2 [SD260] vs Medium: 220 mg/m 2 [MD220] vs Low: 180 mg/m 2 [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/m 2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC.
Competing Interests: Declaration of competing interest Junji Tsurutani received preclinical research funds from Daiichi Sankyo during this study; and outside the submitted work, received honorarium from Novartis, Taiho, Eisai, Chugai, and Kyowa Kirin; personal fees for participating in advisory boards for Eisai and Asahi Kasei; and support for travel expenses from Daiichi Sankyo. Authors 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 and Hirofumi Mukai have no conflict of interest.
(Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: