Clinical Phase I study with an Insulin-like Growth Factor-1 Receptor Inhibitor: Experiences in patients with squamous non-small cell lung carcinoma
2011 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 50, no 3, 441-447 p.Article in journal (Refereed) Published
Background. 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. Patients and methods. 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. Results and discussion. 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.
Place, publisher, year, edition, pages
2011. Vol. 50, no 3, 441-447 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-129608DOI: 10.3109/0284186X.2010.499370ISI: 000288323800017PubMedID: 20698809OAI: oai:DiVA.org:uu-129608DiVA: diva2:344498