Pharmacokinetic parameters of gefitinib predict efficacy and toxicity in patients with advanced non-small cell lung cancer harboring EGFR mutations.

Abstract

PURPOSE:

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.

PATIENTS AND METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Kosuke Mizoguchi, Yoichi Nakamura, Kazumi Sano, Shuntaro Sato, Yoji Ikegami, Kohei Motoshima, Shinnosuke Takemoto, Daiki Ogawara, Hiroaki Senju, Nanae Sugasaki, Takaya Ikeda, Hiroyuki Yamaguchi, Katsumi Nakatomi, Minoru Fukuda, Koichi Izumikawa, Hiroshi Mukae
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 78 Issue 2 Pg. 377-82 (Aug 2016) ISSN: 1432-0843 [Electronic] Germany
• PMID: 27339148 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Antineoplastic Agents
• Quinazolines
• ErbB Receptors
• Gefitinib

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage, adverse effects, pharmacokinetics)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, pathology)
• Chromatography, High Pressure Liquid (methods)
• Disease-Free Survival
• ErbB Receptors (genetics)
• Female
• Gefitinib
• Half-Life
• Humans
• Lung Neoplasms (drug therapy, genetics, pathology)
• Male
• Middle Aged
• Mutation
• Quinazolines (administration & dosage, adverse effects, pharmacokinetics)
• Survival Rate