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Japanese Journal of Clinical Oncology Advance Access originally published online on October 23, 2006
Japanese Journal of Clinical Oncology 2007 37(1):44-48; doi:10.1093/jjco/hyl116
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© 2006 Foundation for Promotion of Cancer Research

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

Kenji Kawada1, Koji Murakami2, Takashi Sato2, Yoshiki Kojima2, Hiromichi Ebi1, Hirofumi Mukai1,, Makoto Tahara1, Kaoru Shimokata3 and Hironobu Minami1

1 Department of Oncology/Hematology, National Cancer Center Hospital East, Kashiwa
2 Department of Diagnostic Radiology, National Cancer Center Hospital East, Kashiwa
3 Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan

For reprints and all correspondence: Hironobu Minami, Department of Oncology/Hematology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. E-mail: hminami{at}east.ncc.go.jp

Received June 26, 2006; accepted August 24, 2006

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.

Key Words: FDG-PET • lapatinib • phase I • pharmacodynamics • biomarker


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