Phase II study of 3-hour infusion of paclitaxel in previously untreated non-small cell lung cancer.
Paclitaxel has clinical activity in non-small cell lung cancer, with response rates of 21 and 24% in a 24-h infusion. Recent clinical studies have shown that a 3-h infusion of the drug with premedication did not result in hypersensitivity reactions, and that neutropenia was milder in the 3-h than in the 24-h schedule. In this Phase II study, we tried to evaluate the efficacy and toxicity of paclitaxel given over 3 h in patients with previously untreated, unresectable stage III or IV non-small cell lung cancer. In addition, we attempted to investigate the pharmacokinetics and pharmacodynamics of the drug. Paclitaxel was administered i.v. over 3 h at a dose of 210 mg/m2 every 3 weeks with premedication of dexamethasone, ranitidine, and diphenhydramine. Heparinized blood samples were obtained from 12 patients for pharmacokinetic studies. Twenty-three (38%) of 60 assessable patients achieved a partial response, with a median duration of 3.2 (range, 2.3-11.1) months. The median survival for all patients was 11.2 months, and the 1-year survival rate was 48%. Thirty (50%) patients developed grade 4 neutropenia. Nonhematological toxicities were mild, except for pulmonary toxicity in one (1.7%) patient who required mechanical ventilatory support for 4 days. The duration of the paclitaxel concentration above 0.1 microM correlated well with the percentage of decrease in the absolute neutrophil count. In conclusion, a 3-h infusion of paclitaxel was safe and probably not less effective than a 24-h infusion.
Sekine
I
I
Division of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa-city, Chiba 277.
Nishiwaki
Y
Y
Watanabe
K
K
Yoneda
S
S
Saijo
N
N
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel