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Drug combination for neuroblastoma?

Thursday November 15th, 2018

A new drug combination has shown “highly significant” results in laboratory tests on neuroblastoma, a European conference will hear today.

The approach used two drugs under clinical trial for adults and was effective at shrinking tumours in tests on mice, report the researchers, led by Professor Murray Norris at the Children's Cancer Institute, an independent medical research institute in Sydney, Australia.

Findings are presented today (15 November) at a meeting of the European Organisation for Research and Treatment of Cancer, the National Cancer Institute, and the American Association for Cancer Research in Dublin, Ireland.

Professor Norris describes the findings as "unusual and highly significant". Both drugs are undergoing clinical trial for several adult cancers.

The team used a genetically modified neuroblastoma mouse model in the lab. These mice spontaneously develop neuroblastomas within weeks after birth. They found that combining the drugs CBL0137 and panobinostat led to the tumours disappearing and not returning.

Professor Norris reports: "This is a highly significant finding as this drug combination is the most effective therapy that we have observed in this neuroblastoma mouse model.

“It is unusual to see this effect, especially in these mice where neuroblastoma develops within seven weeks of birth and is aggressive in nature.

"In fact, the CBL0137/panobinostat combination is more effective than any other current clinical chemotherapy combinations that our laboratory has tested in these mice."

Panobinostat is a histone deacetylase inhibitor already used for multiple myeloma, and CBL0137 belongs to a new class of drugs called curaxins which attack the structure of cancer cells but spare DNA in healthy cells.

Abstract no: 24, Chromatin destabilization by CBL0137 and panobinostat leads to complete tumour regression of childhood neuroblastoma in immunocompetent transgenic mice. Presented on 15 November 2018 at the EORTC-NCI-AACR cancer symposium in Dublin, Ireland.

* A second Australian study has found promise in a new drug combination for colorectal cancer, the conference is to hear.

A team of oncology researchers are reporting on their study of a new therapy for colorectal cancer.

Dr James Kuo and colleagues at Scientia Clinical Research in Sydney, Australia, carried out a phase 1 trial of the two drugs nivolumab and pixatimod. Both drugs stimulate the immune system and were tested on 'microsatellite stable' patients.

Dr Kuo explains that these patients have tumours with fewer signals that alert the immune system to the presence of cancer, explaining their reduced success on checkpoint inhibitors such as nivolumab.

Dr Kuo says: "No patients with microsatellite stable colorectal cancers have been reported to respond to monotherapy with immune checkpoint inhibitor therapy. However, in this study of a new drug combination, we observed clinical benefit in four out of five microsatellite stable patients enrolled, including two demonstrating a reduction in the tumour burden."

Of the 16 patients enrolled in the study, seven have pancreatic cancer, five colorectal cancer, one uterine adenosarcoma, one squamous cell carcinoma, one endometrial carcinoma, and one adrenocortical carcinoma.

Patients were given 240mg of nivolumab every two weeks, and 25mg of pixatimod weekly.

Nivolumab is a programmed cell death protein 1 immune checkpoint inhibitor, which helps T cells recognise and attack cancer cells. Pixatimod is a new drug that stimulates dendritic cells and natural killer cells in the immune system.

Abstract no: 9, Preliminary results from a Phase Ib study of pixatimod (PG545) in combination with nivolumab in patients with advanced solid tumours with an expansion cohort in patients with metastatic pancreatic cancer. Presented on 15 November 2018 at the EORTC-NCI-AACR cancer symposium in Dublin, Ireland.

Tags: Australia | Brain & Neurology | Cancer | Child Health | Europe | Gastroenterology | Pharmaceuticals

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