A phase I trial of carboplatin and etoposide for elderly (>or=75 year-old) patients with small-cell lung cancer.
OBJECTIVE
The combination of carboplatin and etoposide is currently considered the most appropriate regimen for treating elderly patients with small-cell lung cancer (SCLC). Previous reports on elderly patients, 70 years or older, found that the recommended dose was close to that of younger patients. Then, we conducted a phase I study of carboplatin and etoposide in elderly patients, 75 years or older, with SCLC. This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT).


METHODS
Twenty-six patients fulfilling the eligibility criteria, chemotherapy-naive, performance status (PS) of 0-2, age>or=75, and adequate organ functions were enrolled. Patients' characteristics were: male/female=21/5; PS 0/1/2=9/11/6; median age (range)=78 (75-82); and limited/extensive stage=16/10. The patients intravenously received carboplatin with a target AUC of 4 or 5 mg min/ml (Chatelut formula) on day 1 and etoposide at 80-120 mg/m2 on days 1, 2 and 3. Therapy was repeated four times in every 4 weeks.


RESULTS
The MTD of carboplatin/etoposide was AUC=5/80, 4/110, and 4/120. The DLTs were thrombocytopenia, neutropenia, leukopenia, and febrile neutropenia. Overall, grade 4 thrombocytopenia, neutropenia (>or=4 days), leukopenia (>or=4 days), and febrile neutropenia occurred in 27, 20, 7, and 13% of cases at MTD levels, respectively, and 0% at other levels. Twenty of 26 patients showed objective responses (2CR, 18PR; RR=77%).


CONCLUSIONS
A dose of carboplatin of AUC=4 and etoposide of 100 mg/m2 was recommended in this regimen.
Fukuda
Minoru
M
Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, and National Ureshino Hospital, Saga, Japan. mifukuda258@nifty.com
Soda
Hiroshi
H
Soejima
Yoshifumi
Y
Fukuda
Masaaki
M
Kinoshita
Akitoshi
A
Takatani
Hiroshi
H
Kasai
Takashi
T
Nagashima
Seiji
S
Kawabata
Shigeru
S
Doi
Seiji
S
Kohno
Shigeru
S
Oka
Mikio
M
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D003875:Drug Eruptions / Q000209:etiology; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007275:Injections, Intravenous; D008111:Liver Function Tests; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
D005047:Etoposide; D003404:Creatinine; D016190:Carboplatin