Here's some good news for the board (you clowns will love this) A current post has gained some traction about neurotoxicity of 35. I believe the poster is on a good path to opening up dialogue this topic.
I'll add my comment here as apposed to burying it as post #36.
Remember that 35 is currently being reported as salvage therapy and doing OK at that. These are the worst-of-the-worst patients. They've already had front line drugs. All you biochemists know that cells aren't stupid and can creat new defenses to survive. We can postulate that the cells are "more defensive" at the salvage-therapy state and may be less suseptable to damage by, say 35. But at that, 35 has shown "response" which speaks to relative positive effectiveness. If 35 was given to UNTREATED patiens AKA front-line, perhaps it'll have a better chance of "response" without the untoward side effects.
Here's why: 1. Untreated cells may render themselves more susceptable to damage by 35 as apposed to being hit by previous drugs and providing a "resistance" component.
2. Dose is a function of tumor burdon. The current trial is salvage and I'm sure the dosing is higher for these patients by virtue of Pateint tollerance (of collective therapies) resistance cell strains by virtue of previous therapies, and large tumors. Of course heightened side effects are a result of collective therapies as well as single drug. There is no S.E. data out for 35 alone.
Now comes front line 35. Side effects (theoretically) may be lessened since previous treatment effects don't exist. But I'm envisioning that the dosing will be DECREASED since resistant strains may not evolve, and, the bumor burdeon is must lower. If this is true than the side effects experienced within the salvage trials my not hold true for front-line outcomes.
Interesting topics Rick although I don't think you have a good handle on it, nor do I. I think from the good results we see, there is NO cross resistance to other treatments and side effects are mostly a result of the individual drug. As to front-line VS salvage it gets more intriguing. The two obvious (to me) questions is how SGEN-35 will interact with other front-line agents and CD30 expression differences. As to the former, it would be best to schedule RX to enhance the chances for maximum cell kill. This could be a big advantage for 35 being an immunotoxin. It gives another mechanism of action for cell kill, so theoretically there can be expectations for a better outcome than standard therapy when the two are scheduled together for maximum cell kill. As for CD30 expression, I wonder if there is a difference between new and relapsed patients? Often times a primary tumor is polyclonal (or mixed phenotype) and relapsed tumors more uniform. Not sure if this is true for CD30 expression but if it is, that could affect outcome of frontline VS relapsed therapy. Anybody have insight on that?