Phase I study of a weekly infusion of irinotecan hydrochloride (CPT-11) and a 14-day continuous infusion of etoposide in patients with lung cancer: JCOG trial 9408.
BACKGROUND
The aim was to determine the maximum tolerated dose (MTD) and recommended dose of irinotecan hydrochloride (CPT-11) in combination with a 14-day continuous infusion of etoposide in patients with refractory advanced lung cancer (LC), especially small cell lung cancer (SCLC).


METHODS
Etoposide was administered continuously at 25 mg/m2/day for 14 days. The initial dose of CPT-11 was 40 mg/m2 given as a 90 min intravenous infusion on days 1, 8 and 15 and the dose escalation of CPT-11 was planned in increments of 20 mg/m2 until severe or life-threatening toxic effects were observed.


RESULTS
Nine refractory or advanced LC patients (eight at level 1, one at level 2) were entered in this study, of whom two at level 1 were not assessable for toxicity because of patient's refusal and progressive disease. One treatment-related death due to pulmonary toxicity and one patient with hypotension who needed catecholamine for more than 48 h were observed at level 1, a CPT-11 dose of 40 mg/m2. The MTD of CPT-11 was 40 mg/m2. Therapeutic efficacy could be assessed in seven patients, of whom two achieved a partial response.


CONCLUSIONS
This regimen was too toxic and the recommended dose was outside the levels in this study. One has to consider pulmonary toxicity when using CPT-11, especially for patients previously treated with cytotoxic agents for which pulmonary toxicity has been reported.
Fujishiro
M
M
Division of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Shinkai
T
T
Fukuda
M
M
Tamura
T
T
Ohe
Y
Y
Kunitoh
H
H
Nishiwaki
Y
Y
Sekine
I
I
Fukuda
H
H
Saijo
N
N
D000230:Adenocarcinoma / Q000188:drug therapy*; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged
D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D000077146:Irinotecan; D002166:Camptothecin