title: A phase I pilot study of the insulin-like growth factor 1 receptor pathway modulator AXL1717 in combination with gemcitabine HCl and carboplatin in previously untreated, locally advanced, or metastatic non-small cell lung cancer.
abstract: AXL1717 is an orally bioavailable IGF-1R pathway modulator that has been shown to have anti-tumoral effects. The objectives of the present study were to define maximum tolerated dose and the recommended phase II dose (RPTD) of AXL1717 in combination with gemcitabine HCl and carboplatin in non-small cell lung cancer (NSCLC). Patients with previously untreated, locally advanced, or metastatic NSCLC (squamous cell cancer or adenocarcinoma) in good performance status and with preserved major organ functions were enrolled in the study. The study was an open-label phase I study with planned cohorts of three patients per dose level of AXL1717 (215, 290, and 390 mg BID). In total, 12 patients were enrolled in the study, and of these, two were prematurely excluded. AXL1717 was administered at one dose level, 215 mg BID. A total number of 81 unique adverse events were reported. Bone marrow toxicity was reported in 10 out of 12 patients, and this organ class showed the largest number of related events. AXL1717 in combination with gemcitabine HCl and carboplatin is a possible treatment approach in previously untreated, locally advanced, or metastatic non-small cell lung cancer. However, due to the bone marrow toxicity profile shown in the present study, further dose increases of AXL1717 above 215 mg BID will probably not be feasible. Therefore, 215 mg BID constitutes maximum tolerated dose and RPTD.
authors: Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden, georg.h@telia.com.
authors: Georg
authors: G
authors: Holgersson
authors: Stefan
authors: S
authors: Bergström
authors: Johan
authors: J
authors: Harmenberg
authors: Magnus
authors: M
authors: Ringbom
authors: Maria
authors: M
authors: Klockare
authors: Markus
authors: M
authors: Jerling
authors: Simon
authors: S
authors: Ekman
authors: Kristina Lamberg
authors: KL
authors: Lundström
authors: Hirsh
authors: H
authors: Koyi
authors: Eva
authors: E
authors: Brandén
authors: Olle
authors: O
authors: Larsson
authors: Michael
authors: M
authors: Bergqvist
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000556:secondary; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D014018:Tissue Distribution; D000093542:Gemcitabine
chemical_list: C415032:picropodophyllin; D003841:Deoxycytidine; D016190:Carboplatin; D017526:Receptor, IGF Type 1; D011034:Podophyllotoxin; D000093542:Gemcitabine