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
| Autor: | Michael Bergqvist, Georg Holgersson, Johan Harmenberg, Simon Ekman, Hirsh Koyi, Stefan Bergström, Magnus Ringbom, Kristina Lamberg Lundström, Eva Brandén, Olle Larsson, Markus Jerling, Maria Klockare |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Oncology Cancer Research medicine.medical_specialty Lung Neoplasms Maximum Tolerated Dose medicine.medical_treatment Pilot Projects Adenocarcinoma Deoxycytidine Carboplatin Receptor IGF Type 1 Cohort Studies chemistry.chemical_compound Carcinoma Non-Small-Cell Lung Internal medicine Antineoplastic Combined Chemotherapy Protocols Carcinoma Humans Medicine Tissue Distribution Lung cancer Aged Neoplasm Staging Podophyllotoxin Chemotherapy Hematology Performance status business.industry General Medicine Middle Aged Prognosis medicine.disease Gemcitabine chemistry Lymphatic Metastasis Carcinoma Squamous Cell Female business Follow-Up Studies medicine.drug |
| Zdroj: | Medical Oncology. 32 |
| ISSN: | 1559-131X 1357-0560 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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