Phase II trial of amrubicin for treatment of refractory or relapsed small-cell lung cancer: Thoracic Oncology Research Group Study 0301.
OBJECTIVE
This multicenter, phase II study was conducted to evaluate the activity of amrubicin, a topoisomerase II inhibitor, against refractory or relapsed small-cell lung cancer (SCLC).


METHODS
SCLC patients with measurable disease who had been treated previously with at least one platinum-based chemotherapy regimen and had an Eastern Cooperative Oncology Group performance status of 0 to 2 were eligible. Two groups of patients were selected: patients who experienced first-line treatment failure less than 60 days from treatment discontinuation (refractory group), and patients who responded to first-line treatment and experienced disease progression > or = 60 days after treatment discontinuation (sensitive group). Amrubicin was administered as a 5-minute daily intravenous injection at a dose of 40 mg/m2 for 3 consecutive days, every 3 weeks.


RESULTS
Between June 2003 and December 2004, 60 patients (16 refractory and 44 sensitive) were enrolled. The median number of treatment cycles was four (range, one to eight). Grade 3 or 4 hematologic toxicities comprised neutropenia (83%), thrombocytopenia (20%), and anemia (33%). Febrile neutropenia was observed in three patients (5%). Nonhematologic toxicities were mild. No treatment-related death was observed. The overall response rates were 50% (95% CI, 25% to 75%) in the refractory group, and 52% (95% CI, 37% to 68%) in the sensitive group. The progression-free survival, overall survival, and 1-year survival in the refractory group and the sensitive group were 2.6 and 4.2 months, 10.3 and 11.6 months, and 40% and 46%, respectively.


CONCLUSIONS
Amrubicin exhibits significant activity against SCLC, with predictable and manageable toxicities; this agent deserves to be studied more extensively in additional trials.
Onoda
Sayaka
S
Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Masuda
Noriyuki
N
Seto
Takashi
T
Eguchi
Kenji
K
Takiguchi
Yuichi
Y
Isobe
Hiroshi
H
Okamoto
Hiroaki
H
Ogura
Takashi
T
Yokoyama
Akira
A
Seki
Nobuhiko
N
Asaka-Amano
Yoshiko
Y
Harada
Masao
M
Tagawa
Akihiro
A
Kunikane
Hiroshi
H
Yokoba
Masanori
M
Uematsu
Kazutsugu
K
Kuriyama
Takayuki
T
Kuroiwa
Yumi
Y
Watanabe
Koshiro
K
D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000628:therapy*; D010166:Palliative Care; D011788:Quality of Life; D015996:Survival Rate; D016896:Treatment Outcome
D018943:Anthracyclines; D000970:Antineoplastic Agents; C055866:amrubicin