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Dose escalation study of amrubicin and cisplatin with concurrent thoracic radiotherapy for limited-disease small cell lung cancer

  • Midori Shimada
  • Hiroyuki Yamaguchi
  • Minoru FukudaEmail author
  • Hiromi Tomono
  • Noritaka Honda
  • Yosuke Dotsu
  • Hirokazu Taniguchi
  • Hiroshi Gyotoku
  • Hiroaki Senju
  • Shinnosuke Takemoto
  • Takaya Ikeda
  • Katsumi Nakatomi
  • Yoichi Nakamura
  • Seiji Nagashima
  • Takuya Yamazaki
  • Hiroshi Mukae
Original Article

Abstract

Background

Amrubicin and cisplatin is one of the active regimens used to treat patients with extensive-disease (ED)-small cell lung cancer (SCLC), whereas combined therapy involving chemotherapy and concurrent thoracic radiotherapy is the standard treatment for limited-disease (LD)-SCLC.

Purpose

This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of amrubicin and cisplatin with concurrent thoracic radiotherapy (TRT) for LD-SCLC.

Patients and methods

Patients that fulfilled the following eligibility criteria were enrolled: being aged ≤ 75 years and chemotherapy-naïve and having a performance status (PS) of 0–1, LD-SCLC, and adequate organ function. The patients received escalating doses of amrubicin on days 1, 2, and 3, and a fixed 60-mg/m2 dose of cisplatin on day 1. Four cycles of chemotherapy were administered, with each cycle lasting 4 weeks. TRT involving 2 Gy/day, once daily, commenced on day 2 of the first cycle of chemotherapy. The initial dose of amrubicin was 20 mg/m2 (level 1), and the dose was escalated to 25 mg/m2 (level 2) and then 30 mg/m2 (level 3).

Results

Eight patients from three institutions were enrolled at three dose levels. The patients’ characteristics were as follows: male/female: 3/5; median age (range): 68.5 (60–73); PS 0/1: 4/4; stage IIIA/IIIB disease: 3/5. Both level 3 patients experienced DLT (grade 4 neutropenia and/or leukopenia lasting > 4 days). Level 3 was defined as the MTD, and level 2 was recommended as the dose for this regimen. Seven patients exhibited partial responses, and 1 displayed progressive disease (response rate: 88%). The median progression-free survival and overall survival periods were 11.1 and 39.5 months, respectively. No treatment-related deaths occurred.

Conclusions

When this regimen was combined with TRT for LD-SCLC, the MTD was 30 mg/m2 for amrubicin and 60 mg/m2 for cisplatin. In addition, neutropenia and leukopenia were DLT, and doses of 25 mg/m2 for amrubicin and 60 mg/m2 for cisplatin are recommended for this regimen.

Keywords

Amrubicin Cisplatin Small cell lung cancer Radiotherapy 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Midori Shimada
    • 1
    • 2
  • Hiroyuki Yamaguchi
    • 2
  • Minoru Fukuda
    • 2
    • 3
    Email author
  • Hiromi Tomono
    • 1
  • Noritaka Honda
    • 4
  • Yosuke Dotsu
    • 2
  • Hirokazu Taniguchi
    • 2
  • Hiroshi Gyotoku
    • 5
  • Hiroaki Senju
    • 2
  • Shinnosuke Takemoto
    • 2
  • Takaya Ikeda
    • 6
  • Katsumi Nakatomi
    • 7
  • Yoichi Nakamura
    • 8
  • Seiji Nagashima
    • 5
  • Takuya Yamazaki
    • 9
  • Hiroshi Mukae
    • 2
  1. 1.Department of Respiratory MedicineSasebo City General HospitalNagasakiJapan
  2. 2.Department of Respiratory MedicineNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  3. 3.Clinical Oncology CenterNagasaki University HospitalNagasakiJapan
  4. 4.Division of Respiratory Diseases, Department of Internal MedicineJapanese Red Cross Nagasaki Genbaku HospitalNagasakiJapan
  5. 5.Department of Respiratory MedicineNational Hospital Organization Nagasaki Medical CenterNagasakiJapan
  6. 6.Department of Thoracic OncologyNational Cancer Center Hospital EastKashiwaJapan
  7. 7.Department of Respiratory MedicineUreshino Medical CenterUreshinoJapan
  8. 8.Department of Internal MedicineTochigi Cancer CenterUtsunomiyaJapan
  9. 9.Department of Radiological Sciences, Graduate School of Biomedical SciencesNagasaki UniversityNagasakiJapan

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