Phase I dose escalation study of amrubicin plus paclitaxel in previously treated advanced non-small cell lung cancer.
BACKGROUND
We conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD), the recommended dose (RD) and the safety profile of amrubicin (AMR) plus paclitaxel (PTX) combination regimen for patients with previously treated non-small cell lung cancer (NSCLC).


METHODS
PTX was administered at a fixed dose of 150 mg/m(2)/day on day 1 and AMR was intravenously administered at a starting dose of 25 mg/m(2)/day on days 1-3, and this was repeated every 4 weeks. Doses of each drug were planned as follows-level 0, 20/150; level 1, 25/150; level 2, 30/150; level 3, 30/180 AMR mg/m(2) per day/PTX mg/m(2) per day.


RESULTS
Twelve patients were enrolled in this study. The dose-limiting toxicity (DLT) of the regimen was assessed during the first cycle. At level 1, all three patients developed a DLT due to grade 4 neutropenia lasting >4 days, grade 4 thrombocytopenia and grade 3 febrile neutropenia. Therefore, level 1 was considered the MTD and level 0 was selected as the RD. Objective responses were seen in two patients (response rate 16.7 %). Overall disease control rate was 91.7 %.


CONCLUSIONS
The combination of AMR and PTX is a feasible and well-tolerated regimen for the treatment of patients with previously treated advanced NSCLC. Although our study included a small number of patients, encouraging disease control and progression-free survival were achieved at the recommended doses. Further clinical trials are warranted.
Department of Oncology Clinical Development, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan. kkaira1970@yahoo.co.jp.|Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan. kkaira1970@yahoo.co.jp.
Kyoichi
K
Kaira
Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan.
Noriaki
N
Sunaga
Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan.
Hisao
H
Imai
Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan.
Yosuke
Y
Kamide
Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan.
Yasuhiko
Y
Koga
Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan.
Akihiro
A
Ono
Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan.
Tomohito
T
Kuwako
Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan.
Tomomi
T
Masuda
Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan.
Takeshi
T
Hisada
Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan.|Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Tamotsu
T
Ishizuka
Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan.
Masanobu
M
Yamada
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D061605:Administration, Intravenous; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D016879:Salvage Therapy; D015996:Survival Rate
D018943:Anthracyclines; C055866:amrubicin; D017239:Paclitaxel
Amrubicin; Class III β-tubulin; NSCLC; Paclitaxel; Phase I; Topoisomerase II