Phase I trial of carboplatin and etoposide in combination with panobinostat in patients with lung cancer.

Abstract

UNLABELLED:

A phase I trial consisting of panobinostat (a HDAC inhibitor), carboplatin and etoposide was conducted in patients with lung cancer.

PATIENTS AND METHODS:

Patients received carboplatin AUC5 on day 1 and etoposide 100 mg/m(2) on days 1, 2 and 3, every 21 days. Concurrent oral panobinostat was given 3 times weekly on a 2-weeks-on and 1-week-off schedule during the 4-6 cycles of chemotherapy and then continued as maintenance therapy.

RESULTS:

Six evaluable patients were treated at the first dose level of panobinostat (10 mg). Dose-limiting toxicity occurred in two patients (33%) during the first cycle. One patient developed grade 4 thrombocytopenia and another grade 4 febrile neutropenia. Therefore, the study was suspended based on the pre-specified study design. No recommended phase II starting dose was established.

CONCLUSION:

The addition of panobinostat to carboplatin and etoposide was not tolerable at the lowest dose level tested in this trial. Further research and development into this combination is not recommended.

• Authors: Ahmad A Tarhini, Haris Zahoor, Brian McLaughlin, William E Gooding, John C Schmitz, Jill M Siegfried, Mark A Socinski, Athanassios Argiris
• Journal: Anticancer research (Anticancer Res) Vol. 33 Issue 10 Pg. 4475-81 (Oct 2013) ISSN: 1791-7530 [Electronic] Greece
• PMID: 24123018 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Hydroxamic Acids
• Indoles
• Etoposide
• Panobinostat
• Carboplatin

Topics

• Adenocarcinoma (drug therapy, secondary)
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carboplatin (administration & dosage)
• Chemotherapy-Induced Febrile Neutropenia (etiology)
• Early Termination of Clinical Trials
• Etoposide (administration & dosage)
• Humans
• Hydroxamic Acids (administration & dosage)
• Indoles (administration & dosage)
• Lung Neoplasms (drug therapy, pathology)
• Middle Aged
• Panobinostat