Week 197: giving up PI3K+PARP, trying auranofin++

Written by Lars Haakon Soraas

Week 197 in the war on lung cancer has passed. Here are the highlights:

  • As mentioned in last week’s post, Dyanne recently started a combination of two drugs. One was inhibiting PI3K and one was inhibiting PARP. As described previously on this blog, we measure tumor markers CEA and NSE frequently to measure if treatments we try have any effect or not. We have tracked CEA and NSE after Dyanne started these two new drugs and, unfortunately, there are no signs they are working. Due to this, we decided to switch treatments. The charts showing CEA and NSE are shown at the bottom of this post. The yellow marker shows when Dyanne started on the PI3K inhibitor. And a couple of days after this, she started on the PARP inhibitor.
  • We cannot be sure what is the reason the combo failed. Is it because the cancer cells are resistant to the treatment? Or is it because the doses we used were too low? Or was it perhaps because the PI3K inhibitor (an investigational drug) was not doing its job? Due to this uncertainty, we may decide to try the combo again, but using a different PI3K inhibitor that is more proven.
  • We finally got the results from the CT scan Dyanne did on 6th May. It took 3.5 weeks for Oslo University Hospital to make produce the report. And it happened only after I called two senior bosses at the hospital to complain. Given that we have seen that both CEA and NSE have increased rapidly in the past few weeks, the scan result are already kind of outdated. From what we understand, the scan shows improvements in some places, possible deterioration in a couple and stability in yet other places.
  • We also got the results from the MR scan of the brain. The scan was done on 20th May and the results were good. All seems ok in the brain. That was some good news we needed!
  • So, what have we done since stopping the PI3K+PARP combo? Well, we have started a drug combination consisting of the following drugs: auranofin, disulfiram and celecoxib. In addition, Dyanne is continuing with the PARP inhibitor (but at a reduced dose), osimertinib and she is increasing the frequency of the mirtazapine tablets. Auranofin is an old drug used for rheumatoid arthritis and the reason for starting it is twofold. First of all, it did really well in the drug sensitivity testing we did in Finland. Secondly, there are plenty of pre-clinical papers showing it can be a promising anti-cancer drug. As I mentioned in this tweet, scientists already in 1986 found this drug could work against small cell lung cancer cells. And in 2019 some clever scientists, apparently oblivious to the 1986 finding, made the same finding again. Disulfiram is, as some may recall, a drug Dyanne took in December last year. And, we believe, it then caused her an unpleasant episode of delirium. We still believe it can be a promising drug for Dyanne and we are hence trying it again. But at a lower dose, so that we, hopefully, avoid another round of delirium. The drug cocktail was proposed by Dr Richard Kast in the US. He has helped us a lot over the past years and he is also the researcher who has been the driving force behind the CUSP9 drug cocktail approach in glioblastoma.
  • Dyanne has had some fatigue on the auranofin++ drug combo. Apart from this, she has been in good shape.

We will measure CEA and NSE this coming week. If there is no change in trend with the auranofin++ combo, we will probably switch to chemotherapy and do one more round of this.

One of the world’s largest cancer conferences, ASCO, is currently taking place in Chicago, US. I had been looking forward to the conference and had hoped it would provide some good news for lung cancer patients. However, despite all the hype and heat such conferences generate, there seems to be no major advances in lung cancer presented at the conference.

Hope everyone has had a good week!

CEA, yellow marker indicates when PI3K inhibitor was started. PARP inhibitor was started 2 days after that again.
NSE, yellow marker indicates when PI3K inhibitor was started. PARP inhibitor was started 2 days after that again.

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