Combination of irinotecan and etoposide for treatment of refractory or relapsed small-cell lung cancer.
OBJECTIVE
To determine the response rate, survival, and toxicity of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with etoposide, a topoisomerase II inhibitor, in refractory or relapsed small-cell lung cancer (SCLC).


METHODS
Twenty-five patients with refractory or relapsed SCLC were entered onto the trial. All 25 patients had been pretreated with some form of cisplatin-based combination chemotherapy and had also received previous etoposide- or anthracyclinecontaining chemotherapy. The median time off chemotherapy was 6.7 months (range, 0.9 to 23.5). Patients were treated at 4-week intervals using CPT-11 (a starting dose of 70 mg/m2 intravenously on days 1, 8, and 15) plus etoposide (80 mg/m2 intravenously on days 1 to 3), with a subsequent dose based on toxicity. In addition, recombinant human granulocyte colony-stimulating factor (rhG-CSF; 2 microg/kg/d) was given from day 4 to day 21, except on the days of CPT-11 administration.


RESULTS
All patients were assessable for toxicity and survival. Twenty-four patients were assessable for response. There were 14 partial responses (PRs) and three complete responses (CRs), for an overall response rate of 71% (95% confidence interval, 53% to 89%). The median response duration was 4.6 months. Median survival was 271 days. Major toxicities were myelosuppression (predominantly leukopenia) and diarrhea. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 56% and 20% of patients, respectively. Grade 3 to 4 diarrhea was observed in 4%. There was one treatment-related death due to severe myelosuppression.


CONCLUSIONS
A combination of CPT-11 and etoposide with rhG-CSF support is an active therapy against refractory or relapsed SCLC and deserves to be studied more extensively in a phase III trial.
Department of Internal Medicine, Osaka Prefectural Habikino Hospital, Japan.
N
N
Masuda
K
K
Matsui
S
S
Negoro
N
N
Takifuji
K
K
Takeda
T
T
Yana
M
M
Kobayashi
T
T
Hirashima
Y
Y
Kusunoki
S
S
Ushijima
I
I
Kawase
T
T
Tada
H
H
Sawaguchi
M
M
Fukuoka
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D016019:Survival Analysis
D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D000077146:Irinotecan; D002166:Camptothecin