Gefitinib affects functions of platelets and blood vessels via changes in prostanoids balance.
Prostaglandins (PGs) and thromboxane (TX) produced by cyclooxygenase (COX) have a great influence on vascular systems and platelet functions. The serum levels of epidermal growth factor (EGF) and PGs were measured in patients with lung cancer treated with gefitinib, and the influence of EGF on platelet aggregation was investigated. Twenty patients were investigated. The serum level of TXB(2) increased significantly in all patients who received gefitinib for 2 weeks (before vs. after = 94.1 +/- 47.3 vs. 190.9 +/- 54.3, p<0.01). TXB(2) also increased significantly in responders without concurrent chemotherapy (before vs. after = 79.3 +/- 35.5 vs. 194.5 +/- 58.1, p<0.05), but not in non-responders (before vs. after = 106. 5 +/- 65.8 vs. 162.2 +/- 52.8, N.S.). PG 6-keto F1alpha and PGE(2) did not exhibit significant changes. Furthermore, EGF showed no significant change (after vs. before = 234 +/- 35 vs. 276 +/- 72, N.S.). Although there was no correlation between the levels of EGF and TXB(2) (N.S.), the PG 6-keto F2alpha/TXB(2) ratio decreased significantly (before vs. after = 0.054 +/- 0.018 vs 0.033 +/- 0.015, p<0.05). The secondary platelet aggregation observed after high-dose adenosine diphosphate stimulation was inhibited after a 1-minute preincubation with EGF. Platelet aggregation in patients after gefitinib administration tended to accelerate and secondary aggregation was observed after low-dose adenosine diphosphate stimulation. We conclude that careful observation is needed for patients with chronic obstructive pulmonary disease, pulmonary fibrosis, and thromboembolic diseases receiving gefitinib. Furthermore, measurement of prostanoids may be a good predictor of the beneficial and adverse effects. Moreover, the combination of gefitinib with a COX inhibitor that regulates TXA(2)/PGI(2) balance should be evaluated.
Kanazawa
Shigenori
S
First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Yamaguchi
Kazuyuki
K
Kinoshita
Yoshimi
Y
Muramatsu
Mikiko
M
Komiyama
Yutaka
Y
Nomura
Shosaku
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D001808:Blood Vessels / Q000187:drug effects* / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000097:blood; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000097:blood*; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use
D011453:Prostaglandins; D011799:Quinazolines; D004815:Epidermal Growth Factor; D000077156:Gefitinib