Pharmacokinetic results of a phase I trial of sorafenib in combination with dacarbazine in patients with advanced solid tumors
| العنوان: | Pharmacokinetic results of a phase I trial of sorafenib in combination with dacarbazine in patients with advanced solid tumors |
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| المؤلفون: | E. Brendel, Matthias Ludwig, Caroline Robert, Chetan Lathia, Jean-Charles Soria, Stanislas Ropert, Jean-Pierre Armand |
| المساهمون: | Bayer HealthCare AG, Research Center, Bayer Corporation, Institut Gustave Roussy (IGR), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Institut Claudius Regaud, CRLCC Institut Claudius Regaud, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) |
| المصدر: | Cancer Chemotherapy and Pharmacology Cancer Chemotherapy and Pharmacology, Springer Verlag, 2010, 68 (1), pp.53-61. 〈10.1007/s00280-010-1423-9〉 Cancer Chemotherapy and Pharmacology, Springer Verlag, 2010, 68 (1), pp.53-61. ⟨10.1007/s00280-010-1423-9⟩ |
| بيانات النشر: | Springer Nature |
| مصطلحات موضوعية: | Male, Cancer Research, Pyridines, Metabolite, Pharmacology, Toxicology, Tyrosine-kinase inhibitor, chemistry.chemical_compound, 0302 clinical medicine, Neoplasms, AIC, Antineoplastic Combined Chemotherapy Protocols, Medicine, heterocyclic compounds, Pharmacology (medical), ComputingMilieux_MISCELLANEOUS, 0303 health sciences, biology, Benzenesulfonates, Sorafenib, 3. Good health, Dacarbazine, Oncology, Enzyme inhibitor, 030220 oncology & carcinogenesis, Disease Progression, Original Article, Female, medicine.drug, Niacinamide, medicine.drug_class, 03 medical and health sciences, Phase I, Pharmacokinetics, Growth factor receptor, Humans, Protein Kinase Inhibitors, 030304 developmental biology, business.industry, Phenylurea Compounds, Cancer, medicine.disease, Aminoimidazole Carboxamide, chemistry, biology.protein, business |
| الوصف: | Purpose Sorafenib, a multikinase inhibitor of Raf and several growth factor receptors, is under investigation in combination with dacarbazine, a commonly used chemotherapeutic agent for the treatment of many cancers. The current phase I study investigates the effects of sorafenib on the pharmacokinetic (PK) profile of dacarbazine and its metabolite 5-amino-imidazole-4-carboxamide (AIC). (AIC is formed in amounts equimolar to the active alkylating moiety, methane diazohydroxide, which is undetectable by known validated assays.) Methods Patients with advanced solid tumors received intravenous dacarbazine 1,000 mg/m2 on day 1 of a 21-day cycle to evaluate the PK of dacarbazine alone. Sorafenib 400 mg was administered twice daily continuously starting at day 2 of cycle 1. The PK of dacarbazine in the presence of sorafenib was assessed on day 1 of cycle 2. Sorafenib PK was also assessed at steady state. Results PK data were available for 15 of 23 patients. With concomitant administration of sorafenib, the mean AUC and Cmax values of dacarbazine were reduced by 23 and 16%, respectively. Mean AUC and Cmax values of AIC were increased by 41 and 45%, respectively, with individual increases of up to 106 and 136%, respectively. The apparent terminal half-lives of the two compounds were not significantly influenced by sorafenib. Based on coefficients of variation, the AUC and Cmax values for sorafenib and its three metabolites were highly variable with dacarbazine coadministration. Conclusions Concomitant administration of sorafenib and dacarbazine as described above may result in decreased dacarbazine exposure but increased AIC exposure. Electronic supplementary material The online version of this article (doi:10.1007/s00280-010-1423-9) contains supplementary material, which is available to authorized users. |
| اللغة: | English |
| تدمد: | 0344-5704 1432-0843 |
| DOI: | 10.1007/s00280-010-1423-9 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dc5923473861a3868da6680831fe2c26Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....dc5923473861a3868da6680831fe2c26 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 03445704 14320843 |
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| DOI: | 10.1007/s00280-010-1423-9 |