Related Experiment Video
Updated: Mar 13, 2026
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
A phase I trial of panobinostat (LBH589) in patients with metastatic melanoma
Nageatte Ibrahim1,2, Elizabeth I Buchbinder1, Scott R Granter3
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Abstract:
Epigenetic alterations by histone/protein deacetylases (HDACs) are one of the many mechanisms that cancer cells use to alter gene expression and promote growth. HDAC inhibitors have proven to be effective in the treatment of specific malignancies, particularly in combination with other anticancer agents. We conducted a phase I trial of panobinostat in patients with unresectable stage III or IV melanoma. Patients were treated with oral panobinostat at a dose of 30 mg daily on Mondays, Wednesdays, and Fridays (Arm A). Three of the six patients on this dose experienced clinically significant thrombocytopenia requiring dose interruption. Due to this, a second treatment arm was opened and the dose was changed to 30 mg oral panobinostat three times a week every other week (Arm B). Six patients were treated on Arm A and 10 patients were enrolled to Arm B with nine patients treated. In nine patients treated on Arm B, the response rate was 0% (90% confidence interval [CI]: 0-28%) and the disease-control rate was 22% (90% CI: 4-55%). Among all 15 patients treated, the overall response rate was 0% (90% CI: 0-17%) and the disease-control rate was 27% (90% CI: 10-51%). There was a high rate of toxicity associated with treatment. Correlative studies suggest the presence of immune modifications after HDAC inhibition. Panobinostat is not active as a single agent in the treatment of melanoma. Further exploration of this agent in combination with other therapies may be warranted.
Insights
Panobinostat, a histone deacetylase inhibitor, showed no significant efficacy as a single agent for advanced melanoma. High toxicity rates were observed, suggesting combination therapy may be needed for future research.
Area of Science:
- Oncology
- Pharmacology
- Immunology
Background:
- Epigenetic modifications, including those mediated by histone deacetylases (HDACs), are crucial for cancer cell gene expression and growth.
- HDAC inhibitors demonstrate efficacy in certain cancers, often when used with other treatments.
Purpose of the Study:
- To evaluate the safety and efficacy of panobinostat as a single agent in patients with unresectable stage III or IV melanoma.
- To explore potential immune modifications induced by HDAC inhibition.
Main Methods:
- A Phase I clinical trial was conducted with two treatment arms for oral panobinostat.
- Arm A: 30 mg daily (Monday, Wednesday, Friday). Arm B: 30 mg three times a week, every other week, due to toxicity in Arm A.
- Patients with unresectable stage III or IV melanoma were enrolled.
Main Results:
- Six patients were treated in Arm A; three experienced significant thrombocytopenia requiring dose interruption.
- Nine patients were treated in Arm B. The response rate was 0% (90% CI: 0-28%), and the disease-control rate was 22% (90% CI: 4-55%).
- Across all 15 treated patients, the overall response rate was 0% (90% CI: 0-17%), and the disease-control rate was 27% (90% CI: 10-51%). High toxicity was noted.
Conclusions:
- Panobinostat monotherapy is not effective for treating advanced melanoma.
- The observed toxicity profile and lack of efficacy suggest that panobinostat may not be suitable as a standalone treatment.
- Further investigation of panobinostat in combination regimens for melanoma warrants consideration, potentially exploring immune modulation effects.
