Study of paclitaxel and dose escalation of cisplatin in patients with advanced non-small cell lung cancer.
BACKGROUND
We conducted a dose-finding and feasibility study in which we administered a fixed dose 3-h infusion of paclitaxel and an escalating dose of cisplatin in Japanese patients with advanced non-small cell lung cancer.


METHODS
Chemotherapy consisted of fixed dose (210 mg/m(2)) paclitaxel given over 3 h on day 1 and an escalating dose of cisplatin on day 2, every 3-4 weeks. The dose of cisplatin was 40 mg/m(2) at level 1, 60 mg/m(2) at level 2 and 80 mg/m(2) at level 3.


RESULTS
Between October 1999 and February 2001, 24 patients were enrolled and 58 cycles were administered. The major hematological toxicities were leukopenia and neutropenia. Grade 4 neutropenia developed in 83.3%, 66.7% and 83.3% of patients at the dose levels of 1, 2 and 3, respectively. The major non-hematological toxicities consisted of alanine aminotransferase (ALT) elevation and peripheral neuropathy. Grade 3 ALT elevation was observed in two of the 12 patients at level 3, but both recovered within 3 days. The peripheral neuropathy was sensory-dominant and frequent, and it was almost tolerable. The maximum tolerated dose was not identified even at the highest dose of paclitaxel (210 mg/m(2)) and cisplatin (80 mg/m(2)) administered in the study. The recommended dose was determined to be paclitaxel 210 mg/m(2) on day 1 and cisplatin 80 mg/m(2) on day 2, every 3-4 weeks. Seven partial responses were observed in the 24 patients.


CONCLUSIONS
The combination of paclitaxel 210 mg/m(2) and cisplatin 80 mg/m(2) was found to be a well-tolerated active regimen in Japanese patients with advanced non-small cell lung cancer.
Watanabe
Hirokazu
H
Division of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan.
Yamamoto
Noboru
N
Tamura
Tomohide
T
Shimoyama
Tatsu
T
Hotta
Katsuyuki
K
Inoue
Akira
A
Sawada
Masahiro
M
Akiyama
Yoshiko
Y
Kusaba
Hitoshi
H
Nokihara
Hiroshi
H
Sekine
Ikuo
I
Kunitoh
Hideo
H
Ohe
Yuichiro
Y
Kodama
Tetsuro
T
Saijo
Nagahiro
N
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced
D017239:Paclitaxel; D002945:Cisplatin