Looking forward: hope on the horizon?

These days, we rarely look beyond the date of Steve's next three monthly assessment (or at present, his next treatment!).  However, there is one area where I am always keen to look forward to see if there is more hope on the horizon: research into treatments and possible cures for mesothelioma.

In the December 2012 issue of the Journal of Thoracic Oncology, mesothelioma expert Anne Tsao analyzed recent and upcoming directions in mesothelioma research.  She focussed on three main areas of development; anti-angiogenic drugs, immunotherapy and biomarkers.  This is what she has to say:

Anti-angiogenic agents

Anti-angiogenic agents are drugs that prevent tumors from creating new blood vessels (which allows the tumor to spread from its origin).  Researchers are finding great promise in these drugs for mesothelioma patients who meet a very specific set of characteristics. These trials have produced positive responses for sunitinib, bevacizumab/gemcitabine/platinum-based chemotherapy regimens, and the tumor-specific peptide known as NGR-hTNF.

Moving Forward

Researchers have already identified vorinostat as a potential treatment for mesothelioma. This lymphoma drug has produced median survival rates of up to four weeks longer than placebo drugs, but further developmental trials are currently on pause. Once researchers can provide further analysis on the biomarkers that indicate a positive response to vorinostat, they may be able to launch additional studies.

A clinical trial that is currently wrapping up at MD Anderson Cancer Center, USA. The study is one of the first efforts to incorporate pre- and post-treatment biopsies, personalized treatment plans and a novel targeted agent.

Immunotherapy

Many developments in immunotherapy focus on the use of tremelimumab. This human antibody is proving especially useful in patients who do not respond to traditional chemotherapy drugs.  In one study of 22 patients, tremelimumab produced two partial responses, stabilized four patients’ progression and yielded an overall survival of 17.5 months.

Moving forward

In light of the recently completed phase II immunotherapy studies, researchers hope to advance to the next stage in tremelimumab testing. If certain results are achieved, the drug may become an ideal “salvage therapy” for mesothelioma patients who do not respond to first-line treatment.

Biomarkers

The article concluded with an overview of biomarker research. In the last year, this research has included studies of genetic mutations, serum markers, blood-based markers and prognostic tumor markers. Most recently, researchers identified the biomarker, BAP1, which may contribute to patients’ genetic predisposition for non-asbestos-related mesothelioma.

Moving forward

The MD Anderson Cancer Center and the Memorial Sloan-Kettering Cancer Center, USA, will soon open enrollment for a WT-1 vaccine trial. This vaccine may prompt attacks on mesothelioma cells containing the WT-1 biomarker.

Researchers also hope to identify a more accurate prognostic biomarker for mesothelioma. While one team in Boston has identified a four-gene ration test that has decent results, they must adapt the test to account for several limitations (including the lack of real-time results).

UK Clinical Trials

If you are based in the UK, it can't have escaped your notice that the clinical trials referred to in the article are all happening in the USA.  Don't despair!  There are several clinical trials currently recruiting people with mesothelioma in the UK, according to the UK Clinical Trials Gateway (UKCTG) Link top right

NGR-hTNF
This is a study in second line treatment for patients with advanced mesothelioma who have been pre-treated with no more than one pemetrexed (aka Alimta) based chemotherapy regime.  It's currently recruiting in Manchester, Maidstone, Leicester, Northwood, Glasgow, Sutton and London.  

The trial involves a weekly 60 minute IV infusion of the agent, either on its own or in combination with another agent.  It continues until confirmed evidence of disease progression, or unacceptable toxicity occurs. 

Follow the link top right under Clinical Trials for more information, or via the UKCTG website.

ADI-PEG 20 

This trial is currently recruiting in Cambridge, Hull, London, Manchester and Southampton, including patients who have been previously treated with a platinum-based chemotherapy regime.  To be eligible to take part, you need to be tested to see if you are "ASS-negative". 

The trial drug is given weekly for six months.  

For more information, follow the links top right under Clinical Trials or search via the UKCTG website.

HSV1716

This trial is currently recruiting in Sheffield.  It's based on a mutant of the cold sore virus herpes simplex. To be eligible for this trial, you need to have a pleural effusion (aka "fluid on the lung") which is, or could be, treated via an indwelling pleural catheter. The trial drug is delivered directly into the pleural space via this catheter, if I've understood correctly!  

The aim of the trial is to test the safety and tolerability of the drug in a single and repeat doses.  Samples of pleural fluid are collected on day 29 and day 50 for testing evidence of cell death, replication of the virus and changes in the appropriate biomarkers.

For more information, follow the links top right to the UKCTG website and search under Mesothelioma.

Conclusions

Theses advancements may certainly change the way doctors currently treat mesothelioma. Each trial brings us one step closer to an effective treatment – which the mesothelioma community will pursue this year, and each year that follows, until we find a cure.  It WILL happen, one day.