A phase I trial of oral administration of panobinostat in combination with paclitaxel and carboplatin in patients with solid tumors

作者：Jones Suzanne F^*; Infante Jeffrey R; Thompson Dana S; Mohyuddin Adil; Bendell Johanna C; Yardley Denise A; Burris Howard A III

来源：Cancer Chemotherapy and Pharmacology, 2012, 70(3): 471-475.

DOI：10.1007/s00280-012-1931-x

To determine the maximum tolerated doses and dose-limiting toxicities of oral panobinostat in combination with paclitaxel and carboplatin when administered to patients with advanced solid tumors.
Patients initially received panobinostat twice weekly. Following amendment #1, patients received panobinostat three times weekly. Paclitaxel and carboplatin were administered intravenously on day 1 of each 21-day treatment cycle. Dose escalation continued until the maximum tolerated dose was determined. A total of 10 patients were treated at the recommended phase II dose to further assess safety.
Twenty-one patients were enrolled across four different dose levels. The dose-limiting toxicity of the combination regimen was myelosuppression (neutropenia and thrombocytopenia), which often warranted panobinostat dose omissions or reductions. Nearly two-thirds of the patients experienced grade 4 neutropenia or grade 3 or 4 thrombocytopenia. Non-hematologic toxicities consisted primarily of diarrhea, fatigue, and vomiting, which were mild to moderate in intensity. No QTc prolongation was reported. Three partial responses were confirmed in patients with carcinoma of unknown primary (two patients) and non-small-cell lung cancer (one patient). Eleven additional patients reported stable disease as their best response to treatment.
The recommended phase II dose is panobinostat 10 mg orally three times weekly in combination with paclitaxel 175 mg/m(2) and carboplatin AUC 5 administered intravenously on day 1 of every 21-day cycle.

• 出版日期2012-9