I almost forgot Pyrr's excellent systemic response post.
Pyrrhonian Member Level Friday, September 19, 2014 5:37:47 AM
Post # of 19311
I'm not sure how weak it is, Doc. It certainly doesn't have the immediate anti-tumorigenicity that many chemos do--but as those only work as long as the organism can handle them before dying, the comparison may not be a fair one. If RECIST was developed to compare one chemo against another, where do immunotherapies fall into this? We need a new ORR criteria, imo.
If one is diagnosed with fully resectable St I or II cancer, that has been found to have spread to a minority of lymph nodes, they resect the tumor and the nodes and dose the patient with a low toxicity chemo. It is not to further destroy what was already resected but instead to abolish any undetected, very small lesions and transient CRCs. In this it appears to be fairly effective, as many St I cancers have high 5 and 10 year OS rates. However, the more lymph nodes affected and the longer these CRCs had to move about and take up root elsewhere the worse the prognosis. This would seem to counter the idea that those low toxicity chemos do much at all, and rather it is only resection that cures cancer.
In truth, the data may only partially answer whether this is or is not the case, as an increase in OS may need philosophical reframing. Chemos to treat St III and IV cancers usually only add 20%-30% to the patient's lifespan. With added toxicity, and often grave toxicity, does one benefit themselves and their families who must watch this take place in them, to undergo such perils, for a few extra months? To surrender to chemicals and a medical establishment that fails them but not before taking their money and many months of suffering for 3 months of life? I personally would not, and understand that many likewise do not. But I digress..
The point is whether or not DCVax-Direct, in it's very early readout, can accurately be depicted as having a weak or very little systemic response. Those further along in the tx are seeing non-injected lesions shrink and fill with immune cells. Why? This must be seen as a systemic, even if localized response. It is not a result of injection, but immune signaling. Of course it would seem due to cytokine release, which signals to the killer cells to come to where they (the DCs) are--much in the way an inflamed cut on the arm would, destroying bacteria the DCs recognized and displayed to them. After all, being most prevalent in the largest organ in the human body (the skin), this is their primary function. And we would be extinct long ago from deadly, fast proliferating bacteria if not for their evolved capabilities.
From 2 months (4th injection) on, it appears, so far, that a whole body systemic response is also occurring. Distant lesions from 2 months to 4 months (5th injection) stop growing. Why? Are they slowly being devoured from the inside out also? Too soon to tell (scans only), but something is happening.. Are CSCs being found and destroyed by the immune system throughout the body? It would appear so, otherwise, how are no new lesions forming after so many months? Since we are talking about the most deadly, fastest progressing cancers on earth, and to get in the trial patients must only be able to scale the OS hurdle of "life expectation > 3 months." Weak? From what I can tell thus far, I disagree.
Of course, I agree that to say weak one must have a comparator in mind, and yours must be SOC, and the very fast and seemingly "strong" response rates found from aggressive, high toxicity chemos. One example being:
Quote:
Anthracyclines such as doxorubicin, alkylating agents such as cyclophosphamide, antimetabolites such as fluorouracil and methotrexate, and microtubule inhibitors such as the taxanes and vinorelbine. Response rates for these agents range from mid 20% to high 60%.
But then, these partially wrecked tumors always come back. The patients in the DCVax-Direct trial historically have a 99% chance of dying in under 5 years. They are given a 1% to live (actually it's lower, but, let's forget decimals for now). And after 2-4 months of therapy, they have achieved "stabilization of disease" (official RECIST crit) or better. The only one to have received all 6 injections showed some live tumor cells left at his 5th injection biopsy, or 4 months into therapy. 4 months later, and with no additional injections, they took another biopsy and found no live tumor cells. What was happening over those 4 months with no injections?
Of course, these results may change, but I'm seeing a "strong" systemic response at the moment, by my definition of the word. And a synergistic one at that.
