title: 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.
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 and febrile neutropenia without a source. One patient had cerebral infarct that was not attributed to study treatment. All patients achieved a partial response to treatment. At 33 months of follow-up, all patients were still alive. Panobinostat can be combined with palliative-dose RT at doses up to 45 mg twice a week with tolerable toxicity. Dose-limiting toxicities prevented the dose escalation of the panobinostat with CRT.
authors: aCancer Clinical Trials Unit bDepartment of Medical Oncology cDepartment of Radiation Oncology dDepartment of Medical Imaging, Royal Adelaide Hospital eCentre for Cancer Biology, SA Pathology and University of South Australia fDiscipline of Medicine, University of Adelaide, Adelaide, Australia.
authors: Harminder S
authors: HS
authors: Takhar
authors: Nimit
authors: N
authors: Singhal
authors: Raghu
authors: R
authors: Gowda
authors: Michael
authors: M
authors: Penniment
authors: Parineet
authors: P
authors: Takhar
authors: Michael P
authors: MP
authors: Brown
mesh_terms: D000284:Administration, Oral; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D000077767:Panobinostat; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*
chemical_list: D006877:Hydroxamic Acids; D007211:Indoles; D011838:Radiation-Sensitizing Agents; D000077767:Panobinostat