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- Title
Pharmacokinetic parameters of gefitinib predict efficacy and toxicity in patients with advanced non-small cell lung cancer harboring EGFR mutations.
- Authors
Mizoguchi, Kosuke; Nakamura, Yoichi; Sano, Kazumi; Sato, Shuntaro; Ikegami, Yoji; Motoshima, Kohei; Takemoto, Shinnosuke; Ogawara, Daiki; Senju, Hiroaki; Sugasaki, Nanae; Ikeda, Takaya; Yamaguchi, Hiroyuki; Nakatomi, Katsumi; Fukuda, Minoru; Izumikawa, Koichi; Mukae, Hiroshi
- Abstract
<bold>Purpose: </bold>The relationship between plasma concentration and antitumor activity of gefitinib was assessed in patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations.<bold>Patients and Methods: </bold>Plasma trough levels of gefitinib were measured on days 2 (D2) and 8 (D8) by high-performance liquid chromatography in 31 patients. Plasma concentrations of gefitinib were also measured 10 h after the first administration in 21 of these patients to calculate the elimination half-life of gefitinib.<bold>Results: </bold>The median trough levels were: 197 ng/ml 10 h from the first administration of gefitinib; 113 ng/ml on D2; and 358 ng/ml on D8. The median D8/D2 ratio was 2.709, and the median elimination half-life was 15.7 h. The median progression-free survival (PFS) was 273 days, and the median overall survival (OS) was 933 days. A high D8/D2 ratio was significantly correlated with better PFS, though the plasma trough levels on D2 and D8 were not significantly related to PFS. The elimination half-life was not a significant factor for PFS, but it was significantly correlated with high-grade adverse events. Pharmacokinetic parameters were not significantly correlated with OS.<bold>Conclusions: </bold>A high D8/D2 ratio, but not elimination half-life, might be a predictor of better PFS in patients with NSCLC harboring EGFR mutations treated with gefitinib. On the other hand, long elimination half-life was related to high-grade adverse events in these patients. Clinical Trial Registration UMIN000001066.
- Subjects
PHARMACOKINETICS; GEFITINIB; SMALL cell lung cancer; ANTINEOPLASTIC agents; TOXICITY testing; CLINICAL trials; COMPARATIVE studies; EPIDERMAL growth factor; HETEROCYCLIC compounds; HIGH performance liquid chromatography; LUNG cancer; LUNG tumors; RESEARCH methodology; MEDICAL cooperation; GENETIC mutation; PROGNOSIS; RESEARCH; SURVIVAL; TIME; EVALUATION research
- Publication
Cancer Chemotherapy & Pharmacology, 2016, Vol 78, Issue 2, p377
- ISSN
0344-5704
- Publication type
journal article
- DOI
10.1007/s00280-016-3097-4