Phase II and tumor pharmacodynamic study of gefitinib in patients with advanced breast cancer.
OBJECTIVE
To evaluate the antitumor activity and pharmacodynamic/biologic effect of gefitinib 500 mg/day monotherapy in patients with previously treated, advanced breast cancer.


METHODS
In this phase II multicenter trial, the primary objective was assessment of the tumor response rate with gefitinib; secondary objectives included analysis of the pharmacodynamic and biologic profiles in healthy and tumor tissue.


RESULTS
while phosphorylation of mitogen-activated protein kinase was inhibited in both tissues, gefitinib treatment induced p27 and a decrease in Ki67 in skin but not in tumors. Furthermore, gefitinib did not inhibit the activated form of Akt in the tumors.


CONCLUSIONS
This study demonstrates a good correlation between the degree of inhibition of EGFR in skin and in breast tumors. The lack of significant clinical activity of gefitinib in our study population is not due to lack of receptor inhibition in these tumors but rather to lack of EGFR dependence in the tested population.
Baselga
José
J
Medical Oncology Service, Vall d'Hebron University Hospital, P. Vall d'Hebron 119-129 08035 Barcelona, Spain. jbaselga@vhebron.net
Albanell
Joan
J
Ruiz
Amparo
A
Lluch
Ana
A
Gascón
Pere
P
Guillém
Vicente
V
González
Sonia
S
Sauleda
Silvia
S
Marimón
Irene
I
Tabernero
Josep M
JM
Koehler
Maria T
MT
Rojo
Federico
F
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011799:Quinazolines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016879:Salvage Therapy; D012983:Soft Tissue Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D011799:Quinazolines; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases; D000077156:Gefitinib