Phase I-II study of amrubicin and cisplatin in previously untreated patients with extensive-stage small-cell lung cancer.
BACKGROUND
Amrubicin, a totally synthetic 9-amino-anthracycline, demonstrated excellent single-agent activity for extensive-stage small-cell lung cancer (ED-SCLC). The aims of this trial were to determine the maximum-tolerated doses (MTD) of combination therapy with amrubicin and cisplatin, and to assess the efficacy and safety at their recommended doses (RD).


METHODS
Eligibility criteria were patients having histologically or cytologically proven measurable ED-SCLC, no previous systemic therapy, an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ function. Amrubicin was administered on days 1-3 and cisplatin on day 1, every 3 weeks.


RESULTS
Four patients were enrolled at dose level 1 (amrubicin 40 mg/m(2)/day and cisplatin 60 mg/m(2)) and three patients at level 2 (amrubicin 45 mg/m(2)/day and cisplatin 60 mg/m(2)). Consequently, the MTD and RD were determined to be at level 2 and level 1, respectively. The response rate at the RD was 87.8% (36/41). The median survival time (MST) was 13.6 months and the 1-year survival rate was 56.1%. Grade 3/4 neutropenia and leukopenia occurred in 95.1% and 65.9% of patients, respectively.


CONCLUSIONS
The combination of amrubicin and cisplatin has demonstrated an impressive response rate and MST in patients with previously untreated ED-SCLC.
Ohe
Y
Y
Department of Internal Medicine, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. yohe@ncc.go.jp
Negoro
S
S
Matsui
K
K
Nakagawa
K
K
Sugiura
T
T
Takada
Y
Y
Nishiwaki
Y
Y
Yokota
S
S
Kawahara
M
M
Saijo
N
N
Fukuoka
M
M
Ariyoshi
Y
Y
D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged
D018943:Anthracyclines; C055866:amrubicin; D002945:Cisplatin