A phase I/II trial of irinotecan plus amrubicin supported with G-CSF for extended small-cell lung cancer

T. Harada, A. Hamada, M. Shimokawa, K. Takayama, S. Kudoh, K. Maeno, S. Saeki, H. Miyawaki, A. Moriyama, K. Nakagawa, Yoichi Nakanishi

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Abstract

Objective: This study reports the findings of a Phase I/II, cohort, dose-escalation trial of amrubicin and irinotecan with the support of granulocyte colony-stimulation factor. This study aimed to determine the dose-limiting toxicity of the combination and to define the maximum-tolerated dose, as a recommended dose for Phase II trials. We also sought to obtain preliminary data on the efficacy of this combination as a frontline therapy for extensive-disease small-cell lung cancer. Methods: We included 23 chemo-naïve patients with extensive-disease small-cell lung cancer in the trial. The amrubicin dose was escalated from 35 to 40 mg/m2 (Levels 1 and 2, respectively) to determine the dose-limiting toxicity, with an unchanged dose of irinotecan at 50 mg/m2. Results: Of nine patients, three experienced dose-limiting toxicities at Level 1 of prolonged Grade 4 neutropenia, Grade 3 febrile neutropenia and Grade 3 febrile neutropenia with Grade 3 diarrhea. At Level 2, two patients experienced dose-limiting toxicities of Grade 4 neutropenia and Grade 3 neutropenia with Grade 4 diarrhea. The maximum-tolerated doses and recommended doses for amrubicin and irinotecan were therefore determined to be 35 and 50 mg/m2, respectively. The Level 1 trial was then expanded to 21 patients, 14 (70%) of whom showed partial responses to the recommended dose. The median progression-free and overall survival times were 6.37 and 15.21 months, respectively. Conclusions: The combination of amrubicin and irinotecan with the support of granulocyte colony-stimulation factor produced a potent effect in chemo-naïve extensive-disease small-cell lung cancer patients. The use of biomarkers for this regimen may identify patients who are likely to suffer from treatment-ending severe adverse effects.

Original languageEnglish
Article numberhyt198
Pages (from-to)127-133
Number of pages7
JournalJapanese Journal of Clinical Oncology
Volume44
Issue number2
DOIs
Publication statusPublished - Feb 1 2014

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irinotecan
Small Cell Lung Carcinoma
Granulocyte Colony-Stimulating Factor
Neutropenia
Febrile Neutropenia
Maximum Tolerated Dose
Granulocytes
Diarrhea
Disease-Free Survival
amrubicin
Biomarkers

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Harada, T., Hamada, A., Shimokawa, M., Takayama, K., Kudoh, S., Maeno, K., ... Nakanishi, Y. (2014). A phase I/II trial of irinotecan plus amrubicin supported with G-CSF for extended small-cell lung cancer. Japanese Journal of Clinical Oncology, 44(2), 127-133. [hyt198]. https://doi.org/10.1093/jjco/hyt198

A phase I/II trial of irinotecan plus amrubicin supported with G-CSF for extended small-cell lung cancer. / Harada, T.; Hamada, A.; Shimokawa, M.; Takayama, K.; Kudoh, S.; Maeno, K.; Saeki, S.; Miyawaki, H.; Moriyama, A.; Nakagawa, K.; Nakanishi, Yoichi.

In: Japanese Journal of Clinical Oncology, Vol. 44, No. 2, hyt198, 01.02.2014, p. 127-133.

Research output: Contribution to journalArticle

Harada, T, Hamada, A, Shimokawa, M, Takayama, K, Kudoh, S, Maeno, K, Saeki, S, Miyawaki, H, Moriyama, A, Nakagawa, K & Nakanishi, Y 2014, 'A phase I/II trial of irinotecan plus amrubicin supported with G-CSF for extended small-cell lung cancer', Japanese Journal of Clinical Oncology, vol. 44, no. 2, hyt198, pp. 127-133. https://doi.org/10.1093/jjco/hyt198
Harada, T. ; Hamada, A. ; Shimokawa, M. ; Takayama, K. ; Kudoh, S. ; Maeno, K. ; Saeki, S. ; Miyawaki, H. ; Moriyama, A. ; Nakagawa, K. ; Nakanishi, Yoichi. / A phase I/II trial of irinotecan plus amrubicin supported with G-CSF for extended small-cell lung cancer. In: Japanese Journal of Clinical Oncology. 2014 ; Vol. 44, No. 2. pp. 127-133.
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abstract = "Objective: This study reports the findings of a Phase I/II, cohort, dose-escalation trial of amrubicin and irinotecan with the support of granulocyte colony-stimulation factor. This study aimed to determine the dose-limiting toxicity of the combination and to define the maximum-tolerated dose, as a recommended dose for Phase II trials. We also sought to obtain preliminary data on the efficacy of this combination as a frontline therapy for extensive-disease small-cell lung cancer. Methods: We included 23 chemo-na{\"i}ve patients with extensive-disease small-cell lung cancer in the trial. The amrubicin dose was escalated from 35 to 40 mg/m2 (Levels 1 and 2, respectively) to determine the dose-limiting toxicity, with an unchanged dose of irinotecan at 50 mg/m2. Results: Of nine patients, three experienced dose-limiting toxicities at Level 1 of prolonged Grade 4 neutropenia, Grade 3 febrile neutropenia and Grade 3 febrile neutropenia with Grade 3 diarrhea. At Level 2, two patients experienced dose-limiting toxicities of Grade 4 neutropenia and Grade 3 neutropenia with Grade 4 diarrhea. The maximum-tolerated doses and recommended doses for amrubicin and irinotecan were therefore determined to be 35 and 50 mg/m2, respectively. The Level 1 trial was then expanded to 21 patients, 14 (70{\%}) of whom showed partial responses to the recommended dose. The median progression-free and overall survival times were 6.37 and 15.21 months, respectively. Conclusions: The combination of amrubicin and irinotecan with the support of granulocyte colony-stimulation factor produced a potent effect in chemo-na{\"i}ve extensive-disease small-cell lung cancer patients. The use of biomarkers for this regimen may identify patients who are likely to suffer from treatment-ending severe adverse effects.",
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AU - Kudoh, S.

AU - Maeno, K.

AU - Saeki, S.

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AU - Nakanishi, Yoichi

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