The Currently Incurable Scientist: Putting Out the Inflammation Fire
The September edition of my monthly The Currently Incurable Scientist column has published on the Fight Colorectal Cancer website. It briefly discusses in layman’s terms the profound roles chronic inflammation is believed to play in cancer patients, including:
- Direct impacts on facilitating tumor growth & spread
- Impacts on helping tumors evade and hide from the immune system making the tumor immunologically “cold”
- Systemic effects on the patient’s body including e.g. loss of appetite & lean body mass (“cachexia”)
The column also discusses a novel experimental anti-inflammatory drug MABp1 (Xilonix) currently being tested in a global randomized Phase 3 trial in CRC patients (NCT01767857).
As I have done before, I wanted to use my personal blog to offer an unofficial extended Director’s Cut & behind-the-scenes Blu-Ray bonus features for the monthly column…
First, some science 🙂
Scientists have been studying anti-inflammatories (e.g. NSAIDS) in CRC patients for years, including basic aspirin, Celebrex (celecoxib) as well as novel anti-inflammatory strategies – which is the subject of this month’s column. Although trial results have been mixed, advances in understanding have been made (e.g. it looks like aspirin use impacts not only CRC recurrence rates but also survival stats, in particular for patients with PIK3CA (p110a) mutations – as published in the New England Journal of Medicine). It feels to me that the potential for this general strategy has been far from fully exploited as of yet. It is a very active area of research though!
Me, myself & I
I myself have taken a NSAID daily for over 2 years now. Although I have a PIK3CA mutation, do I know if it is slowing down my cancer progression? There is no way for me to know. But looking at the risk/potential benefit ratio – after discussing with my MD, I made the personal choice to take one, even with incomplete clinical data. For drugs with an acceptable risk/potential benefit ratio – Stage IV patients do not have the luxury of waiting for complete clinical data packages to be generated…
The clinical trial I highlighted in this month’s column is an experimental anti-inflammatory drug named MABp1 (Xilonix) which blocks Interleukin 1-α. Interleukin 1-α was an interesting choice of target for the developing company to go after, it does not seem like the most obvious choice to me, at least from published data. That is the nature of science however and why novel anti-inflammatory strategies beyond simple aspirin should be tested in the clinic. They impact the inflammatory process at different nodes in complex pathways and only through clinical data will it be known which strategy helps cancer patients the most.
There were signs of potential Xilonix clinical activity, in particular in CRC patients, in its Phase 1 trial published in the journal The Lancet Oncology (link) along with a related commentary from one of the world experts in Interleukin 1 biology (link). There were signs of potential survival improvement as well as increases in quality of life. Interpretation of the data is limited however due to the small numbers of patients in the trial as well as there being no placebo comparison arm.
At the end of the day…
If the Phase 3 clinical results are positive, importantly in comparison with the placebo arm and after vetting by peer review – this would illustrate perfectly some truths of new drug discovery:
- At the end of the day, clinical data trumps all pre-existing preclinical hypotheses and dogma. This is especially true in very complex situations e.g. the impacts of blocking various inflammation mechanisms on many different pathways in a cancer patient’s body.
- It takes guts to develop a drug acting against such a unique target, although presumably they had internal non-published data to support their decision.
I can’t tell the future how the trial will turn out but I certainly wish them the best. Stage IV CRC is desperately in need of new therapeutics and if successful, this one could be unique because it may show not only anti-cancer effects but with an increase in quality of life.
It is that last line which feels the most important to me. When I talk 1-on-1 to fellow cancer patients who are watching drugs currently in trials, at first I was surprised by how much excitement and interest there was in Xilonix. This strong interest came up time and time again, second only to the potential long term remissions theoretically possible with an immunotherapy.
This clearly shows a true patient need and desire that I believe scientists should listen to. Quantity of life is important but quality of life also needs to be actively addressed. Xilonix gets so much attention from patients because it hopes to both extend life but importantly also simultaneously improve quality of life as well. This would be a much different clinical experience for CRC patients than the traditional cytotoxic chemotherapy cocktails which are the current backbone therapies for CRC!
If successful, addressing both quantity as well as quality of life would be something that all of us CRC patients would cheer for – so I wish them all the best and hope the trial is successful!