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正电子发射断层扫描用于评估拉帕替尼(一种ErbB1和ErbB2酪氨酸激酶双重抑制剂)在晚期肿瘤患者中活性的前瞻性研究。

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.

作者信息

Kawada Kenji, Murakami Koji, Sato Takashi, Kojima Yoshiki, Ebi Hiromichi, Mukai Hirofumi, Tahara Makoto, Shimokata Kaoru, Minami Hironobu

机构信息

Department of Oncology/Hematology, National Cancer Center Hospital East, Kashiwa, Japan.

出版信息

Jpn J Clin Oncol. 2007 Jan;37(1):44-8. doi: 10.1093/jjco/hyl116. Epub 2006 Oct 23.

Abstract

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.

摘要

背景

为了评估氟代脱氧葡萄糖正电子发射断层扫描(FDG-PET)在评估分子靶向药物抗肿瘤疗效中的作用,我们前瞻性地对接受拉帕替尼(一种ErbB1和ErbB2酪氨酸激酶双重抑制剂)治疗的患者进行了FDG-PET和CT检查以评估疗效。

方法

在一项I期研究中,拉帕替尼以每日一次口服给药,剂量范围为1200至1800毫克。在治疗前、治疗开始后1、2和3个月以及此后每2个月进行CT和FDG-PET检查。

结果

对8例患有各种实体瘤的患者共进行了29次FDG-PET检查,并将肿瘤中的代谢活性评估为SUVmax。通过CT评估的最佳反应如下:1例部分缓解,4例疾病稳定和3例疾病进展。在1例曲妥珠单抗耐药的乳腺癌患者中观察到部分缓解,其SUVmax较基线下降了60%。在最佳反应为疾病稳定的所有4例患者中,治疗开始后1个月SUVmax下降了6%-42%。在1例结肠癌患者中观察到疾病长期稳定(10个月),其SUVmax下降了42%。在疾病进展的患者组中,3例患者中有2例SUVmax升高。

结论

FDG-PET检测到接受拉帕替尼治疗有临床获益的患者肿瘤代谢活性降低。因此,FDG-PET可能有助于评估拉帕替尼等分子靶向药物。

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