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Phase I and pharmacokinetic study of docetaxel, irinotecan, and celecoxib in patients with advanced non-small cell lung cancer

Argiris, Athanassios ; Kut, Victoria ; Luong, Lynn ; Avram, Michael J

Investigational new drugs, 2006-05, Vol.24 (3), p.203-212 [Periódico revisado por pares]

United States: Springer Nature B.V

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Título:
Phase I and pharmacokinetic study of docetaxel, irinotecan, and celecoxib in patients with advanced non-small cell lung cancer
Autor: Argiris, Athanassios ; Kut, Victoria ; Luong, Lynn ; Avram, Michael J
Assuntos: Adult ; Aged ; Anticancer properties ; Antineoplastic Agents, Phytogenic - administration & dosage ; Antineoplastic Agents, Phytogenic - adverse effects ; Antineoplastic Agents, Phytogenic - pharmacokinetics ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Antitumor activity ; Camptothecin - administration & dosage ; Camptothecin - adverse effects ; Camptothecin - analogs & derivatives ; Camptothecin - pharmacokinetics ; Cancer therapies ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - metabolism ; Cardiovascular disease ; Celecoxib ; Cell division ; Chemotherapy ; Coronary artery ; Coronary artery disease ; COX-2 inhibitors ; Cyclooxygenase 2 Inhibitors - administration & dosage ; Cyclooxygenase 2 Inhibitors - adverse effects ; Cyclooxygenase 2 Inhibitors - pharmacokinetics ; Cyclooxygenase-2 ; Cytotoxicity ; Diarrhea ; Docetaxel ; Drug dosages ; Drug Interactions ; Enzymes ; FDA approval ; Female ; Health risks ; Heart diseases ; Humans ; Irinotecan ; Kinases ; Laboratories ; Lung cancer ; Lung Neoplasms - drug therapy ; Lung Neoplasms - metabolism ; Male ; Metastasis ; Middle Aged ; Myocardial infarction ; Nausea ; Neutropenia ; Non-small cell lung carcinoma ; Patients ; Pharmaceuticals ; Pharmacokinetics ; Pharmacology ; Pneumonitis ; Pyrazoles - administration & dosage ; Pyrazoles - adverse effects ; Pyrazoles - pharmacokinetics ; Response rates ; Risk analysis ; Risk factors ; Small cell lung carcinoma ; Sulfonamides - administration & dosage ; Sulfonamides - adverse effects ; Sulfonamides - pharmacokinetics ; Taxoids - administration & dosage ; Taxoids - adverse effects ; Taxoids - pharmacokinetics ; Toxicity
É parte de: Investigational new drugs, 2006-05, Vol.24 (3), p.203-212
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Descrição: We studied the toxicities, potential pharmacokinetic interactions, and preliminary antitumor activity of the combination of docetaxel and irinotecan with celecoxib, a selective cyclooxygenase-2 inhibitor. Eligible patients had advanced non-small lung cancer (NSCLC) with measurable disease, good performance status, and adequate end organ function. Docetaxel and irinotecan were administered intravenously on days 1 and 8, every 21 days, and their doses were escalated on successive patient cohorts at three dose levels: 30/50, 30/60, and 35/60 (doses in mg/m2). Celecoxib was administered at a starting dose of 400 mg orally twice daily without interruption, beginning on day 2 of cycle 1. Pharmacokinetic studies were performed on day 1 of cycle 1 and day 1 of cycle 2. Seventeen patients with advanced NSCLC were enrolled and collectively received 78 cycles of therapy. Diarrhea was the most common toxicity; it was noted in 13 patients (76%). Dose-limiting toxicities occurred at dose level 1 (myocardial infarction in a patient with multiple coronary artery disease risk factors) and dose level 3 (grade 4 neutropenia with fatal urosepsis). Other major toxicities were: grade 3 neutropenia (2 patients); grade 3/4 diarrhea (3/1); grade 3 nausea (2); grade 2 rash (1); and grade 3 pneumonitis (1). The maximum tolerated dose was at dose level 3, i.e., docetaxel 35 mg/m2 and irinotecan 60 mg/m2 on days 1 and 8, plus celecoxib 400 mg twice daily, repeated every 21 days. Five of 15 evaluable patients achieved an objective response. The pharmacokinetics of docetaxel were not altered by celecoxib. However, we observed an 18% increase in the average elimination clearance of irinotecan coincident with the addition of celecoxib. The addition of celecoxib to docetaxel and irinotecan was generally well tolerated but unpredictable fatal toxicity occurred. Diarrhea was the most common toxicity. Antitumor activity was promising. The alteration of irinotecan pharmacokinetic parameters observed may not be clinically relevant.
Editor: United States: Springer Nature B.V
Idioma: Inglês

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Phase I and pharmacokinetic study of docetaxel, irinotecan, and celecoxib in patients with advanced non-small cell lung cancer

Argiris, Athanassios ; Kut, Victoria ; Luong, Lynn ; Avram, Michael J

United States: Springer Nature B.V

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