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T. Harada, A. Hamada, M. Shimokawa, K. Takayama, S. Kudoh, K. Maeno, S. Saeki, H. Miyawaki, A. Moriyama, K. Nakagawa, Y. Nakanishi, A Phase I/II Trial of Irinotecan Plus Amrubicin Supported with G-CSF for Extended Small-cell Lung Cancer, Japanese Journal of Clinical Oncology, Volume 44, Issue 2, February 2014, Pages 127–133, https://doi.org/10.1093/jjco/hyt198
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Abstract
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.
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.
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.
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.
- select the dosage, dosage form or route of administration
- small cell carcinoma of lung
- chemotherapy regimen
- neutropenia
- diarrhea
- granulocyte colony-stimulating factor
- biological markers
- phase 2 clinical trials
- granulocytes
- irinotecan
- febrile neutropenia
- toxic effect
- generalized illness
- amrubicin
- partial response