A phase I study of vorinostat in combination with bortezomib in patients with advanced malignancies
| العنوان: | A phase I study of vorinostat in combination with bortezomib in patients with advanced malignancies |
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| المؤلفون: | Joel M. Reid, Dona Alberti, Jill M. Kolesar, Jens C. Eickhoff, Rebecca Marnocha, Renee M. McGovern, Howard H. Bailey, Zhisheng Jiang, Igor Espinoza-Delgado, Steven Attia, Matthew M. Ames, John J. Wright, George Wilding, Anne M. Traynor, Tien Hoang, William R. Schelman, Kyle D. Holen |
| المصدر: | Investigational New Drugs. 31:1539-1546 |
| بيانات النشر: | Springer Science and Business Media LLC, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Adult, Male, Oncology, medicine.medical_specialty, Maximum Tolerated Dose, Nausea, Cmax, Pharmacology, Hydroxamic Acids, Article, Bortezomib, Young Adult, Pharmacokinetics, Neoplasms, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Pharmacology (medical), Vorinostat, Aged, business.industry, Soft tissue sarcoma, Middle Aged, medicine.disease, Boronic Acids, Histone Deacetylase Inhibitors, Pyrazines, Toxicity, Female, medicine.symptom, Hyponatremia, business, medicine.drug |
| الوصف: | Background A phase I study to assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and antitumor activity of vorinostat in combination with bortezomib in patients with advanced solid tumors. Methods Patients received vorinostat orally once daily on days 1–14 and bortezomib intravenously on days 1, 4, 8 and 11 of a 21-day cycle. Starting dose (level 1) was vorinostat (400 mg) and bortezomib (0.7 mg/m2). Bortezomib dosing was increased using a standard phase I dose-escalation schema. PKs were evaluated during cycle 1. Results Twenty-three patients received 57 cycles of treatment on four dose levels ranging from bortezomib 0.7 mg/m2 to 1.5 mg/m2. The MTD was established at vorinostat 400 mg daily and bortezomib 1.3 mg/m2. DLTs consisted of grade 3 fatigue in three patients (1 mg/m2,1.3 mg/m2 and 1.5 mg/m2) and grade 3 hyponatremia in one patient (1.5 mg/m2). The most common grade 1/2 toxicities included nausea (60.9 %), fatigue (34.8 %), diaphoresis (34.8 %), anorexia (30.4 %) and constipation (26.1 %). Objective partial responses were observed in one patient with NSCLC and in one patient with treatment-refractory soft tissue sarcoma. Bortezomib did not affect the PKs of vorinostat; however, the Cmax and AUC of the acid metabolite were significantly increased on day 2 compared with day 1. Conclusions This combination was generally well-tolerated at doses that achieved clinical benefit. The MTD was established at vorinostat 400 mg daily × 14 days and bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day cycle. |
| تدمد: | 1573-0646 0167-6997 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ea29229ff2c9fc20b1f31eb6792844ea https://doi.org/10.1007/s10637-013-0029-6 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ea29229ff2c9fc20b1f31eb6792844ea |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15730646 01676997 |
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