Phase II study of Amrubicin combined with carboplatin for thymic carcinoma and invasive thymoma: North Japan Lung Cancer group study 0803.
BACKGROUND
There has been no standard chemotherapy for advanced or recurrent thymic malignancies including thymic carcinoma (TC) and invasive thymoma (IT), though platinum and anthracycline have been reported as effective agents for the treatment of these diseases. The objective of this study was to evaluate the efficacy and safety of the combination of amrubicin (AMR), a new anthracycline agent, and carboplatin (CBDCA) in patients with advanced thymic malignancies.


METHODS
Patients with histologically confirmed thymic malignancies received AMR (35 mg/m, days 1-3) and CBDCA (area under the curve 4.0, day 1) every 3 weeks. Patients who had received previous chemotherapy were treated with a reduced dose of AMR (30 mg/m). The primary end point was objective response rate (ORR), and secondary endpoints were progression-free survival, overall survival, and toxicity profile.


RESULTS
From December 2008 to October 2012, 51 patients (33 TC and 18 IT) were enrolled. The median number of treatment cycles was four in each group. The ORR and progression-free survival were 30% (95% confidence interval, 14-46) and 7.6 months in the TC group, and 17% (95% confidence interval, 0-34) and 7.6 months in the IT group, respectively. The ORR of TC patients without previous chemotherapy (n = 19) was 42%. Although grade 3 or 4 hematological toxicities were common including neutropenia (82%) and febrile neutropenia (22%), these were transient and manageable. Nonhematological toxicities were moderate and no treatment-related death was observed.


CONCLUSIONS
The combination of AMR with CBDCA was active for TC with acceptable toxicity, although it was not effective for IT. Further investigation of this regimen for advanced TC is warranted.
*Department of Respiratory Medicine, Tohoku University Hospital, Sendai, Japan; †Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan; ‡Department of Respiratory Medicine, Hokkaido Cancer Center, Sapporo, Japan; §Department of Respiratory Medicine, Saitama University International Medical Center, Saitama, Japan; ‖Department of Respiratory Medicine, Shikoku Cancer Center, Matsuyama, Japan; ¶Department of Respiratory Medicine, Iwakuni Medical Center, Iwakuni, Japan; #Department of Respiratory Medicine, Miyagi Cancer Center, Natori, Japan; **First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan; ††Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Okayama, Japan; ‡‡Department of Thoracic Surgery, Senboku Kumiai General Hospital, Daisen, Japan; and §§South Miyagi Medical Center, Miyagi, Japan.
Akira
A
Inoue
Shunichi
S
Sugawara
Masao
M
Harada
Kunihiko
K
Kobayashi
Toshiyuki
T
Kozuki
Shoichi
S
Kuyama
Makoto
M
Maemondo
Hajime
H
Asahina
Akiko
A
Hisamoto
Taku
T
Nakagawa
Katsuyuki
K
Hotta
Toshihiro
T
Nukiwa
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D013945:Thymoma / Q000188:drug therapy* / Q000473:pathology; D013953:Thymus Neoplasms / Q000188:drug therapy* / Q000473:pathology
D018943:Anthracyclines; C055866:amrubicin; D016190:Carboplatin