Section of Oncology, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Sweden.
Acta Oncol. 2011 Apr;50(3):441-7. doi: 10.3109/0284186X.2010.499370. Epub 2010 Aug 11.
Inhibition of the Insulin-like Growth Factor-1 receptor (IGF-1R) has resulted in extensive anti-tumor effects. Picropdophyllin (PPP, AXL1717) is a small-molecule inhibitor of the IGF-1R without inhibition of closely related receptors including the insulin receptor and has shown extensive effects against a wide range of tumors in animals. PPP is currently tested as an orally administrated single agent treatment in an open-label combined Phase I/II clinical study in advanced cancer patients with solid tumors which progress in spite of several lines of treatment.
The first part (Phase IA) consisted of single day BID dosing every three weeks with consecutive dose escalations. The second part (Phase IB) consists of seven days or longer BID dosing every three weeks, dosing range being 520-700 mg BID. Non-progressing patients could continue treatment within a compassionate use setting.
The present report describes our experience with the four patients with progressive squamous non-small cell lung cancer (NSCLC) that have received treatment with PPP. Despite more than seven months of PPP treatment as third or fourth line treatment, the reported patients did not develop any additional metastases. Furthermore, CT scans as well as (18)FDG-Positron Emission Tomography (PET) scans of the patients demonstrated large central necrotic areas, which may suggest tumor response. At the same time, the study drug is so far well tolerated. The phenomenon of necrosis in the tumors suggestive of tumor response has not been reported before in anti-IGF-1R treatment and will be subject to further studies in the present clinical trial.
抑制胰岛素样生长因子-1 受体（IGF-1R）已产生广泛的抗肿瘤作用。 Picropdophyllin（PPP，AXL1717）是 IGF-1R 的小分子抑制剂，不会抑制密切相关的受体，包括胰岛素受体，并在动物中对广泛的肿瘤显示出广泛的作用。PPP 目前作为一种口服单药治疗，在一项开放标签的联合 I/II 期临床研究中，在进展期癌症患者中进行测试，这些患者尽管接受了多线治疗，但仍有实体瘤进展。
第一部分（IA 期）包括每三周连续剂量递增的单日 BID 给药。第二部分（IB 期）包括每三周 BID 给药 7 天或更长时间，剂量范围为 520-700mg BID。非进展患者可以在同情使用的情况下继续治疗。
本报告描述了我们在接受 PPP 治疗的 4 例进展性鳞状非小细胞肺癌（NSCLC）患者中的经验。尽管作为三线或四线治疗，患者接受了超过七个月的 PPP 治疗，但未发现任何额外的转移。此外，患者的 CT 扫描以及（18）FDG-正电子发射断层扫描（PET）扫描显示出较大的中央坏死区域，这可能提示肿瘤反应。同时，研究药物到目前为止耐受性良好。在抗 IGF-1R 治疗中，肿瘤坏死提示肿瘤反应的现象以前没有报道过，将在本临床试验中进一步研究。
