***Warning, long post*** Bob, thanks for the thoughtful reply. The problem with sequential attack is that there will usually be a few mutants left over resistant to the first treatment. They then proliferate, at some stage developing another mutation, resistant to the second treatment type. So the second treatment kills all but the few mutants, which then go on to proliferate, which allows yet another mutant type to arise, resistant to the third treatment type. Which is not applied until disease progression. And these days, lymphoma progression is still detected on a macro basis, using chest xrays, blood counts or palpation rather than molecular detection systems, which at least are being developed.
So it is too often a matter of shutting the stable door after the horse has bolted.
Since treatments are usually, like most things, most effective with the first part of the dose, with less and less additional effect as the dose is increased more and more, it seems that with I131 treatments, where the limiting factor is radiation damage to good cells, it would be better to use two treatment types rather than one. That way, for a given level of toxicity, there would be most antigen attachment to lymphoma cells. The old law of diminishing returns business in action. That way, there should be a synergistic cure rate as the cancer cells which would normally escape the first treatment and go on to develop another mutation, would be killed by the simultaneous second treatment type.
Since they shouldn't be mutually exclusive, unlike Adriamycin and radiation for example, which can't be given simultaneously, the cure rate for the initial treatment should be about 70% better than for either alone. So instead of say an 80% cure rate for a stage 1A diffuse large B-cell CD20 type, for either treatment alone, [the same as with surgical removal of the primary tumour and 3 doses of CHOP] with twin treatment at reduced doses to maintain the same collateral damage level, there should be something like a 90% cure rate because. That's the theory anyway and born out by other cocktail treatments for similar problems. But as you say, the proof is in the clinial trials. Theories abound and fail on test.
It does seem to be almost self-evident to me though.
In the example you mentioned, Rituxan and Bexxar, it seems that if Rituxan alone results in 90% of cancerous B-cell destruction in strongly CD20 positive people, then there are only 10% as many cancer cells left to deal with. So it should take a much reduced dose of Bexxar to reduce the remaining 10% to zero. If that dose is only 20% of the Bexxar only dose, then that would leave room for Oncolym at 20% to be used too, which would attach to the remaining very few cancerous cells with the Oncolym antigens. Total radiation much reduced. I don't think these monoclonal antibodies are synergistically destructive to normal cells, so less damage and improved cancer cell kill rates.
And the earlier the better, to avoid proliferation of mutants and further metastases and more mutations, which is the real problem in cancer as golfdad97 has pointed out several times.
The concept of 'watch and wait' is only valid because of dose limiting toxicity in chemotherapy which can only be used a few times before killing the person. So better to wait until the disease has progressed to relatively intolerable levels, then use the few attempts available to knock the disease back, which at least delays progression to death.
As for research money, it seems too much dependency is on tax dollars and donations. If people invest expecting a profit, they are more likely to find cures than making donations and paying taxes. It will instil financial discipline on people conducting the research. Look at the rabid attention by shareholders to corporate actions in Techniclone's case. Life and money are super hot buttons to people. In the case of tax funded research, you can imagine how much more languid and unfocussed would be the approach. The same for foundations. There is just not the intensity as is gained by the making a buck.
In New Zealand there is almost no 'for profit' research because of the state, university and foundation approach, which depends on reluctantly given tax and donation dollars. They run ads here on cancer week, to raise money through donations - then people give out daffodils, seeking donations, which would be $5 or $20 type amounts. Far more would be given to research if the giver owned a piece of the action, thereby both curing cancer, having a say in the matter, and making some money as well if successful.
Maybe they wouldn't put ALL their money on such risky research, but many people would put 10% of their investment money in.
There is a lady I know here who does research into melanoma and other things. She is thinking of quitting and flipping hamburgers or something because funding is so hard to come by, pay is not that hot, hours are long to justify funding. She is highly qualified, does excellent research, but is demoralized - not with the work, but with the ambience. That would be a couple of decades of knowledge and ideas down the drain. [She isn't really going to flip hamburgers, but you know what I mean].
Thanks for the tip on searching Yahoo! That's more or less what I do. But I include a few others.
For those knowledgeable in the field of cancer, I'm not holding myself out to be an expert. Please tell me what's wrong or expand on anything I write.
What do you reckon, we buy a licence from Coulter, IDEC and Techniclone for each of their products [or two if one wants to try to go it alone], form a company, hire some clinicians, get some protocols, do some trials and make a fortune? We can omit the first class fares, mahogany, repriced options and stuff, spending all the money on getting people cured. When the proof is there, take bids from CNN and others for an exclusive story, then sell stock over the Web. Produce barrels of the stuff, cure a few million people. THEN the board, managers and staff can get their bonus payments.
Of course Techiclone and those companies could cut out the middle men and form a joint venture themselves for cocktail trials. A bit like Qualcomm and Sony did with Qualcomm Personal Electronics, using the different strengths and funding from each.
Just some thoughts,
Maurice |
