Prospective study of positron emission tomography for evaluation of the activity of lapatinib, a dual inhibitor of the ErbB1 and ErbB2 tyrosine kinases, in patients with advanced tumors.
BACKGROUND
To evaluate the role of FDG-PET in assessing anti-tumor efficacy of molecular targeted drugs, we prospectively performed FDG-PET and CT for response evaluation in patients treated with lapatinib, a dual inhibitor of ErbB1 and ErbB2 tyrosine kinases.


METHODS
Lapatinib was given orally once a day at doses ranging from 1200 to 1800 mg in a phase I study. CT and FDG-PET were performed before treatment, and at 1, 2 and 3 months after the initiation of the treatment and every 2 months thereafter.


RESULTS
A total of 29 FDG-PET examinations were performed in eight patients with various solid tumors and the metabolic activity in the tumor was evaluated as SUVmax. The best responses, as assessed by CT, were as follows; one partial response, four stable disease and three disease progression. The partial response was observed in a patient with trastuzumab-resistant breast cancer, whose SUVmax was decreased by 60% from baseline. In all of the four patients whose best response was stable disease, the SUVmax was decreased by 6-42% one month after the start of treatment. Prolonged stable disease (10 months) was observed in a patient with colon cancer, whose SUVmax was decreased by 42%. In the patient group with disease progression, SUVmax was increased in two out of three patients.


CONCLUSIONS
FDG-PET detected decreases in the metabolic activity of the tumors in patients who experienced clinical benefits on treatment with lapatinib. Thus, FDG-PET may be useful for the evaluation of molecular targeted drugs, such as lapatinib.
Kawada
Kenji
K
Department of Oncology/Hematology, National Cancer Center Hospital East, Kashiwa, Japan.
Murakami
Koji
K
Sato
Takashi
T
Kojima
Yoshiki
Y
Ebi
Hiromichi
H
Mukai
Hirofumi
H
Tahara
Makoto
M
Shimokata
Kaoru
K
Minami
Hironobu
H
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D000077341:Lapatinib; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D066246:ErbB Receptors; D019788:Fluorodeoxyglucose F18; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases