Back to Search
Start Over
Phase IB trial of ixabepilone and vorinostat in metastatic breast cancer
- Source :
- Breast Cancer Research and Treatment. 167:469-478
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- To translate promising preclinical data on the combination of vorinostat and ixabepilone for metastatic breast cancer (MBC) into clinical trials. We conducted a randomized two-arm Phase IB clinical trial of ascending doses of vorinostat and ixabepilone in prior -treated MBC patients. To determine the maximum tolerated dose (MTD), 37 patients were randomized to schedule A: every-3-week ixabepilone + vorinostat (days 1–14), or schedule B: weekly ixabepilone + vorinostat (days 1–7; 15–21) Pharmacokinetics were assessed. Nineteen additional patients were randomized to schedule A or B and objective response rate (ORR), clinical benefit rate (CBR), toxicity, progression-free survival (PFS), and overall survival (OS) were assessed. The schedule A MTD was vorinostat 300 mg daily (days 1–14), ixabepilone 32 mg/m2 (day 2); 21-day cycle 27% dose-limiting toxicities (DLTs). The schedule B MTD was vorinostat 300 mg daily (days 1–7; 15–21), ixabepilone 16 mg/m2 (days 2, 9, 16); 28-day cycle; no DLTs. Vorinostat and ixabepilone clearances were 194 L/h and 21.3 L/h/m2, respectively. Grade 3 peripheral sensory neuropathy was reported in 8% (A) and 21% (B) of patients. The ORR and CBR were 22 and 22% (A); 30 and 35% (B). Median PFS was 3.9 (A) and 3.7 (B) months. OS was 14.8 (A) and 17.1 (B) months. We established the MTD of vorinostat and ixabepilone. This drug combination offers a novel therapy for previously treated MBC patients. The potential for lower toxicity and comparable efficacy compared to current therapies warrants further study.
- Subjects :
- Adult
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Drug-Related Side Effects and Adverse Reactions
Maximum Tolerated Dose
Breast Neoplasms
Hydroxamic Acids
Disease-Free Survival
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Breast cancer
Pharmacokinetics
Internal medicine
medicine
Humans
Vorinostat
Aged
business.industry
Ixabepilone
Drug Synergism
Middle Aged
medicine.disease
Metastatic breast cancer
Histone Deacetylase Inhibitors
Clinical trial
Treatment Outcome
030104 developmental biology
chemistry
Epothilones
030220 oncology & carcinogenesis
Maximum tolerated dose
Toxicity
MCF-7 Cells
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 15737217 and 01676806
- Volume :
- 167
- Database :
- OpenAIRE
- Journal :
- Breast Cancer Research and Treatment
- Accession number :
- edsair.doi.dedup.....04c328fc1f0a12c15dda6b3a48fc214a