The efficacy and toxicity of cabazitaxel for treatment of docetaxel-resistant prostate cancer correlating with the initial doses in Japanese patients

Naoki Terada,
Toshiyuki Kamoto,
Hiromasa Tsukino,
Shoichiro Mukai,
Shusuke Akamatsu,
Takahiro Inoue,
Osamu Ogawa,
Shintaro Narita,
Tomonori Habuchi,
Shinichi Yamashita,
Koji Mitsuzuka,
Yoichi Arai,
Shuya Kandori,
Takahiro Kojima,
Hiroyuki Nishiyama,
Yoshiaki Kawamura,
Yuki Shimizu,
Toshiro Terachi,
Motohiko Sugi,
Hidefumi Kinoshita,
Tadashi Matsuda,
Yusuke Yamada,
Shingo Yamamoto,
Hiromi Hirama,
Mikio Sugimoto,
Yoshiyuki Kakehi,
Toshihiko Sakurai and
Norihiko TsuchiyaEmail author

BMC Cancer201919:156

https://doi.org/10.1186/s12885-019-5342-9

Received: 19 October 2018
Accepted: 1 February 2019
Published: 15 February 2019

Open Peer Review reports

Abstract

Background

We analyzed the efficacy and toxicity of cabazitaxel (CBZ) at high and low initial doses in Japanese patients with docetaxel-resistant castration-resistant prostate cancer (CRPC).

Methods

We retrospectively evaluated 118 patients who received CBZ for docetaxel-resistant CRPC in 10 university hospitals in Japan between 2014 and 2016. The rate of decrease of prostate-specific antigen (PSA), adverse events, progression-free survival (PFS), and overall survival (OS) were compared between patients receiving initially high (≥22.5 mg/m2, n = 36) and low (≤20 mg/m2, n = 80) CBZ doses. Factors associated with survival and grade 4 neutropenia were evaluated.

Results

PSA values decreased by > 50% in 22 patients (19%), with a higher frequency in the high-dose group than in the low-dose group (29 and 14%, P = 0.073). The median PFS time for the all-patient, high- and low-dose groups was 2.8 months (95% confidence interval [CI] 1.9–4.4), 2.1 months (1.2–5.5), and 3.0 months (2.0–4.4), respectively (P = 0.904). The median OS times were 16.3 months (95% CI 9.7–30.9), 30.9 months (11.8–47.4), and 10.2 months (8.6–20), respectively (P = 0.020). In multivariate analyses, PFS was significantly associated with existing bone metastasis at diagnosis (P = 0.005) and OS with PSA > 100 ng/ml (P = 0.007), hemoglobin < 12 g/dl (P = 0.030), and low initial CBZ dose (P = 0.030). Grade 4 neutropenia occurred in 53 patients (45%) and was associated with a low CBZ dose (hazard ratio 0.21, 95% CI 0.08–0.59, P = 0.002).

Conclusions

CBZ at a higher initial dose may have similar response rate and response duration, but longer survival duration after treatment with higher toxicity than a lower initial dose for docetaxel-resistant CRPC in Japanese patients.