Research

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Whilst most aspects of Ken's treatment utilise well established surgical practices and chemotherapy regimens, there are more recent advances in the treatment of mCRC that are less well understood. In considering these other treatments Ken has decided to further investigate the potential benefit of each candidate treatment so that the benefit can be properly weighed against the inherent risk.

Chemotherapy

In parallel with the initial regimen of Folfox6+Avastin, research into alternative drugs has been undertaken. The prime alternatives are;

  • Trifluridine-tipiracil. This is a newly approved treatment that could offer greater effectivity. Because it is relatively new it is not readily recommended for treatment.
  • Regorafenib is a new drug that could produce significant benefits. Its relative newness acts against it being selected without evidence of it being effective.
  • Irinotecan is an established treatment in FOLFIRI or IFL regimens. But profiling of the tumour has shown the cancer to have low Topoisomerase 1 levels implying that it is unlikely to realise substantial benefits.

These drugs together with 5-FU (current principal part of Folfox6 regimen) as a comparator form the list that are to be studied. The resected primary tumour is grafted into immune-suppressed mice prior to application of the selected drug. The rate of change of the tumour volume is an indicator of the effectiveness of the drug against Ken's specific cancer characteristics. These tests are being performed by Champions Oncology, with results expected early in 2017.

POS-16202B

The list now comprised the control (no drug), 5-FU, Regorafenib and Irinotecan. The tests successfully completed at the end of April with the final report being issued.

This report summarises the results of the tests as both Irinotecan and Regorafenib resulting in stable disease and with disease progression under 5-FU. The following chart, extracted from the report indicates the relative benefits of each drug.

Immunotherapy

There are two aspects of immunotherapy that are showing promise. The first is the dual use of checkpoint inhibitors. This is still under active research and progress is being monitored.

The second is the use of Dendritic Cell Vaccines. Whilst therapies such as Adoptive Cell Transfer have indicated strong adverse side effects, DCV studies have shown that they are well tolerated. Although DCV therapy has not been approved for the treatment of mCRC, there are clinics that provide such therapy in Germany and Mexico. Literature search of the internet has indicated that the current state of the art (that has been widely studied) for DCV would consist of;

  • Pre-treatment with Temozolomide to deplete the Treg cells and reduce the immune suppression response to the DCV.
  • DCV generated by harvesting monocytes (dendritic cell progenitors) from the blood, differentiated and matured using compounds selected to optimise the desired immune response, primed using tumour lysate and introduced intravenously.

A less studied form of DCV (but indications show that it could be more potent) is based on directly harvesting the dendritic cells from the blood.

Research into the potential use of DCV is to be a combination of academic and expert opinion to confirm or critique this perspective on DCV, propose the optimal immune response and suggest compounds for the differentiation and maturation processes. Secondly, academic and expert opinion will be sought on the DCV's that are currently available and a comparison with the 'optimal' will be made.

Contact Details

+ 44 (0)1843 822555

georgina.molineaux@heli-charter.com

Address

Sapphire House
Merlin Way
Manston
Kent
CT12 5FE
United Kingdom

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