Phase I dose-escalation study of aflibercept in combination with docetaxel and cisplatin in patients with advanced solid tumours
| Autor: | Karen Soussan-Lazard, Nicolas Isambert, P Fumoleau, Gilles Freyer, Véronique Trillet-Lenoir, Benoit You, Sylvie Zanetta, Claire Falandry, S Assadourian, Samira Ziti-Ljajic, Laure Favier |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Oncology Cancer Research medicine.medical_specialty Neutropenia Recombinant Fusion Proteins Docetaxel Pharmacology Drug Administration Schedule angiogenesis chemistry.chemical_compound Neoplasms Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Dose escalation Humans In patient neoplasms Fatigue Aged Aflibercept Cisplatin business.industry aflibercept Middle Aged medicine.disease Vascular endothelial growth factor Clinical trial Receptors Vascular Endothelial Growth Factor chemistry Clinical Study anti-VEGF therapy Female Taxoids business therapeutics VEGF trap medicine.drug |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/bjc.2012.304 |
| Popis: | Background: This phase I cohort study investigated aflibercept (vascular endothelial growth factor (VEGF) trap) plus docetaxel and cisplatin in patients with advanced solid tumours. Methods: Patients received intravenous aflibercept 4, 5, or 6 mg kg−1 with docetaxel and cisplatin (75 mg m−2 each) on day 1 of a 3-week cycle until progressive disease or unacceptable toxicity. Primary objectives were determining cycle 1 dose-limiting toxicities (DLTs) and the aflibercept recommended phase II trial dose (RP2D) for this combination. Results: During the dose-escalation phase (n=16), there were two DLTs of febrile neutropenia (at 4 and 5 mg kg−1). Granulocyte colony-stimulating factor prophylaxis was subsequently recommended. The RP2D of aflibercept was established at 6 mg kg−1 and administered to 14 additional patients. The most frequent grade 3/4 adverse events (AEs) were neutropenia (43.3%), stomatitis (20.0%), asthenia/fatigue (20.0%), and hypertension (16.7%). All-grade AEs associated with VEGF blockade included epistaxis (83.3%), dysphonia (70.0%), proteinuria (53.3%), and hypertension (50.0%). There were five partial responses (16.7%) and 18 cases of stable disease (60.0%) (lasting >3 months in 10 patients). There were no pharmacokinetic (PK) interactions between the three drugs. Conclusion: Aflibercept 6 mg kg−1 with docetaxel and cisplatin 75 mg m−2 every 3 weeks is the RP2D based on tolerability, antitumour activity, and PKs. |
| Databáze: | OpenAIRE |
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