Phase II study of amrubicin combined with carboplatin for refractory relapsed small-cell lung cancer: North Japan Lung Cancer Group Trial 0802.
BACKGROUND
Amrubicin (AMR), a new anthracycline agent, has shown promising results for advanced small-cell lung cancer (SCLC), although the efficacy of AMR alone against refractory relapsed SCLC is insufficient. This study was conducted to evaluate the safety and efficacy of the combination of AMR and carboplatin (CBDCA) in patients with refractory relapsed SCLC.


METHODS
Patients with advanced SCLC who relapsed within 90 days after the completion of first-line chemotherapy received AMR (30mg/m(2), days 1-3) and CBDCA (area under the curve 4.0mgmL(-1)min(-1), day 1) every 3 weeks. The primary endpoint of this study was the overall response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival, and the toxicity profile. Assuming that an ORR of 45% in eligible patients would indicate potential usefulness and an ORR of 20% would be the lower limit of interest, with α=0.10 and β=0.10, at least 24 patients were required.


RESULTS
Among 29 eligible patients, the ORR was 34% (90% confidence interval, 20-48). The median PFS was 3.5 months, whereas the median survival time was 7.3 months. The most common grade 3-4 toxicity was neutropenia (79%), although only one patient (3%) suffered from febrile neutropenia. Non-hematological toxicities were of moderate severity and no treatment-related death was observed.


CONCLUSIONS
This is the first prospective study of AMR combined with CBDCA for refractory relapsed SCLC, which was effective and well tolerated. However, further investigation of this regimen is warranted.
Department of Pulmonary Medicine, Sendai Kousei Hospital, 4-15 Hirose-machi, Aoba-ku, Sendai 980-0873, Japan. Electronic address: yousukekawashima3@yahoo.co.jp.
Yosuke
Y
Kawashima
Department of Respiratory Medicine, Tohoku University Hospital, 1-1 Seiryou-machi, Aoba-ku, Sendai 980-8574, Japan. Electronic address: akinoue@idac.tohoku.ac.jp.
Akira
A
Inoue
Department of Pulmonary Medicine, Sendai Kousei Hospital, 4-15 Hirose-machi, Aoba-ku, Sendai 980-0873, Japan. Electronic address: swara357@cat-v.ne.jp.
Shunichi
S
Sugawara
First Department of Medicine, Hokkaido University School of Medicine, Kita 15-jo Nishi 7-chome, Kita-ku, Sapporo 060-8638, Japan. Electronic address: soizumi@med.hokudai.ac.jp.
Satoshi
S
Oizumi
Department of Respiratory Medicine, Miyagi Cancer Center, 47-1 Nodayama, Medeshima-shiote, Natori 981-1293, Japan. Electronic address: maemondo-ma693@miyagi-pho.jp.
Makoto
M
Maemondo
Department of Respiratory Medicine, Hirosaki Central Hospital, 3-1 Yoshino-machi, Hirosaki 036-8188, Japan. Electronic address: hppokudera@gmail.com.
Koichi
K
Okudera
Department of Respiratory Medicine, Isawa Hospital, 61 Ryugababa, Mizusawa-ku, Oshu 023-0864, Japan. Electronic address: toshi@isawa-hosp.mizusawa.iwate.jp.
Toshiro
T
Suzuki
Division of Respirology, NTT Medical Center Tokyo, 5-9-22 Higashi Gotanda, Shinagawa-ku, Tokyo 141-8625, Japan. Electronic address: usui@east.ntt.co.jp.
Kazuhiro
K
Usui
Department of Respiratory Medicine, Hokkaido Cancer Center, 2-3-54 Kikusui 4-jo, Shiroishi-ku, Sapporo 003-0804, Japan. Electronic address: mharada@sap-cc.go.jp.
Masao
M
Harada
Division of Pulmonary Medicine, Allergy, and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka 020-8505, Japan. Electronic address: carcinoma@nifty.com.
Naoto
N
Morikawa
Department of Respiratory Medicine, Aomori Prefectural Central Hospital, 2-1-1 Higashitukurimichi, Aomori 030-8553, Japan. Electronic address: yukihiro_hasegawa@med.pref.aomori.jp.
Yukihiro
Y
Hasegawa
Department of Respiratory Medicine, Tohoku University Hospital, 1-1 Seiryou-machi, Aoba-ku, Sendai 980-8574, Japan. Electronic address: beambitious0529@yahoo.co.jp.
Ryota
R
Saito
Department of Pulmonary Medicine, Sendai Kousei Hospital, 4-15 Hirose-machi, Aoba-ku, Sendai 980-0873, Japan. Electronic address: ishimoto@crest.ocn.ne.jp.
Osamu
O
Ishimoto
Department of Respiratory Medicine, Tohoku University Hospital, 1-1 Seiryou-machi, Aoba-ku, Sendai 980-8574, Japan. Electronic address: sakatomo@idac.tohoku.ac.jp.
Tomohiro
T
Sakakibara
First Department of Medicine, Hokkaido University School of Medicine, Kita 15-jo Nishi 7-chome, Kita-ku, Sapporo 060-8638, Japan. Electronic address: asahinah@huhp.hokudai.ac.jp.
Hajime
H
Asahina
South Miyagi Medical Center, 38-1 Nishi, Ogawara, Shibata 989-1253, Japan. Electronic address: toshinkw47@gmail.com.
Toshihiro
T
Nukiwa
D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011446:Prospective Studies; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy*; D016896:Treatment Outcome
D018943:Anthracyclines; C055866:amrubicin; D016190:Carboplatin
Amrubicin; Phase II trial; Refractory relapse; Small-cell lung cancer