Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study
| Autor: | R. Ehrenberg, Klaus Mross, C.-H. Köhne, Gunnar Folprecht, Susanne Hamann, J. Kuhlmann, Martin Kornacker, Dirk Strumberg, Beate Schultheis, R. Fischer, O. Boix, Jürgen Krauss, John Lettieri, U. T. Hacker |
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| Rok vydání: | 2013 |
| Předmět: |
Oncology
Adult Male medicine.medical_specialty Adolescent Organoplatinum Compounds Pyridines Leucovorin colorectal cancer chemotherapy combination therapy Folinic acid chemistry.chemical_compound Young Adult FOLFOX Internal medicine Regorafenib Antineoplastic Combined Chemotherapy Protocols Gastrointestinal Tumors medicine Humans Aged Aged 80 and over business.industry Phenylurea Compounds Hematology Original Articles Middle Aged Chemotherapy regimen digestive system diseases Oxaliplatin Irinotecan Treatment Outcome Tolerability chemistry FOLFIRI Camptothecin Female regorafenib Fluorouracil business Colorectal Neoplasms tyrosine kinase inhibition medicine.drug |
| Zdroj: | Annals of Oncology |
| ISSN: | 1569-8041 |
| Popis: | Background Metastatic colorectal cancer (mCRC) is commonly treated with 5-fluorouracil, folinic acid, and oxaliplatin or irinotecan. The multitargeted kinase inhibitor, regorafenib, was combined with chemotherapy as first- or second-line treatment of mCRC to assess safety and pharmacokinetics (primary objectives) and tumor response (secondary objective). Patients and methods Forty-five patients were treated every 2 weeks with 5-fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h, folinic acid 400 mg/m2, and either oxaliplatin 85 mg/m2 or irinotecan 180 mg/m2. On days 4–10, patients received regorafenib 160 mg orally once daily. Results The median duration of treatment was 108 (range 2–345 days). Treatment was stopped for adverse events or death (17 patients), disease progression (11 patients), and consent withdrawal or investigator decision (11 patients). Six patients remained on regorafenib at data cutoff (two without chemotherapy). Drug-related adverse events occurred in 44 patients [grade ≥3 in 32 patients: mostly neutropenia (17 patients) and leukopenia, hand–foot skin reaction, and hypophosphatemia (four patients each)]. Thirty-three patients achieved disease control (partial response or stable disease) for a median of 126 (range 42–281 days). Conclusion Regorafenib had acceptable tolerability in combination with chemotherapy, with increased exposure of irinotecan and SN-38 but no significant effect on 5-fluorouracil or oxaliplatin pharmacokinetics. |
| Databáze: | OpenAIRE |
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