Phase I study of amrubicin plus cisplatin and concurrent accelerated hyperfractionated thoracic radiotherapy for limited-disease small cell lung cancer: protocol of ACIST study.

Abstract

BACKGROUND:

Etoposide plus cisplatin (EP) combined with concurrent accelerated hyperfractionated thoracic radiotherapy (AHTRT) is the standard treatment strategy for unresectable limited-disease (LD) small cell lung cancer (SCLC), which has remained unchanged for over two decades. Based on a previous study that confirmed the non-inferiority of amrubicin (AMR) plus cisplatin (AP) when compared with EP for extensive-disease (ED) SCLC, we have previously conducted a phase I study assessing AP with concurrent TRT (2 Gy/time, once daily, 50 Gy in total) for LD-SCLC therapy. Our findings revealed that AP with concurrent TRT could prolong overall survival to 39.5 months with manageable toxicities. Therefore, we plan to conduct a phase I study to investigate and determine the effect of AP combined with AHTRT, recommended dose (RD), maximum tolerated dose (MTD), and dose-limiting toxicity (DLT) of AP in patients with LD-SCLC.

METHODS:

Treatment-naive patients with LD-SCLC, age between 20 and 75 years, who had a performance status of 0 or 1 and adequate organ functions will be enrolled. For chemotherapy, cisplatin 60 mg/m2 /day (day 1) and AMR (day 1 to 3) will be administered with AHTRT (1.5 Gy/time, twice daily, 45 Gy in total). The initial AMR dose is set to 25 mg/m2 /day. RD and MTD will be determined by evaluating toxicities.

DISCUSSION:

Based on our previous study, the initial dose of AMR 25 mg/m2 is expected to be tolerated and acceptable. Here, we aim to determine whether treatment with AP and concurrent AHTRT would be an optimal choice with manageable toxicities for LD-SCLC.

• Authors: Kazumasa Akagi, Hirokazu Taniguchi, Minoru Fukuda, Takuya Yamazaki, Sawana Ono, Hiromi Tomono, Takayuki Suyama, Midori Shimada, Hiroshi Gyotoku, Shinnosuke Takemoto, Hiroyuki Yamaguchi, Yosuke Dotsu, Hiroaki Senju, Hiroshi Soda, Takashi Mizowaki, Yoshio Monzen, Takaya Ikeda, Seiji Nagashima, Yutaro Tasaki, Daisuke Nakamura, Kazutoshi Komiya, Katsumi Nakatomi, Eisuke Sasaki, Koichi Hirakawa, Hiroshi Mukae
• Journal: Thoracic cancer (Thorac Cancer) Vol. 13 Issue 16 Pg. 2404-2409 (08 2022) ISSN: 1759-7714 [Electronic] Singapore
• PMID: 35808894 (Publication Type: Clinical Trial Protocol, Journal Article)
• Copyright: © 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Chemical References

• Anthracyclines
• Etoposide
• amrubicin
• Cisplatin

Topics

• Adult
• Aged
• Anthracyclines
• Chemoradiotherapy (adverse effects)
• Cisplatin (therapeutic use)
• Clinical Trials, Phase I as Topic
• Etoposide
• Humans
• Lung Neoplasms (therapy)
• Middle Aged
• Small Cell Lung Carcinoma (therapy)
• Young Adult