Phase I study evaluating the safety and efficacy of oral panobinostat in combination with radiotherapy or chemoradiotherapy in patients with inoperable stage III non-small-cell lung cancer

Anti-cancer Drugs
Harminder S TakharMichael P Brown

Abstract

Panobinostat is a radiosensitizing agent and targets the epigenetics of malignancy. This phase I study evaluated the safety and efficacy of combining oral panobinostat with radiotherapy (RT) or chemoradiotherapy (CRT) in patients with inoperable stage III non-small-cell lung cancer. This study had a parallel dose-escalating design combining oral panobinostat twice a week (dose escalations 20, 30, 45 mg) with either palliative RT (group A) or radical CRT (group B) using a standard chemotherapy protocol of cisplatin and etoposide. In group A (RT), nine recruited patients received treatment with oral panobinostat (doses 20, 30, 45 mg) with RT. Two serious adverse events, rapid atrial fibrillation and tracheo-oesophageal fistula, were not attributable to study treatment. The most common grade 3/4 toxicities were thrombocytopenia and lymphopenia, which resolved promptly after cessation of panobinostat. The disease control rate was 66%, the progression-free survival was 3 months and the median overall survival was 9 months. In group B (CRT), panobinostat dose was not escalated beyond 20 mg because of infection-related complications. Serious adverse events included opportunistic infection associated with treatment-related lymphopenia ...Continue Reading

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Citations

Oct 19, 2016·Clinical Epigenetics·Angel R de Lera, A Ganesan
Feb 25, 2017·Journal of Pediatric Hematology/oncology·Zhihong J WangMiller Steven
May 17, 2017·Scientific Reports·Leleesha SamaraweeraHayley M McDaid
Jul 2, 2017·Clinical Pharmacokinetics·Mathilde Van VeggelPaul Hamberg
Jan 8, 2017·Biomaterials·Leoni A Kunz-SchughartSuman Pokhrel
Jun 10, 2021·Clinical Epigenetics·Catarina Macedo-SilvaLucia Altucci

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