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

Thorac Cancer. 2022 Aug;13(16):2404-2409. doi: 10.1111/1759-7714.14555. Epub 2022 Jul 8.

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.

Keywords: amrubicin; chemotherapy; radiotherapy; small cell lung cancer.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • 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

Substances

  • Anthracyclines
  • Etoposide
  • amrubicin
  • Cisplatin