RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:Stay focused on the factsYou are right that 300 mg/m2 could be a good dose, but it would be the case only with a proof of concept. Also, yes having the highest possible dosage is not a necissity, if you have the proof of concept. As I said in my previous message, at this point if the 420 mg/m2 was the MTD, it would be in itself a very strong indication that we have a proof of concept because I think it would be impossible to tlerate that dose if the concept was not working. At 300 mg/m2, we cannot be sure, and 300 mg/m2 is not even confirmed as a tolerable dose. All the idea that lower doses are valid only works if the concept works. That leads us to patient #2. OK, he gor 4 cycles, but three of these four cycles were at doses below the MTD of docetaxel alone. So it tells us nothing about the proof of concept, and why was it stopped after one cycle at 300 mg/m2? In my opinion, we cannot read anything into that. At this point this trias is a black box with known input, an very little know on the output. Also, Marsolais can say all he wants that the concept of having the highest possible dose is nor correct, but he is right and wrong on that. If you have the proof of concept he is right to a certain extent, but at this point a 300 mg/m2 dose sows doubt about the existence of a proof of concept. Also, even with a proof, you ideally want the MTD to be as high as possible because it would give you a wider therapeutic window, and would allow long term treatment at lower doses. If 300 mg/m2 is tolerable, but very close to the MTD, or the MTD, it means that you would need to go quite low on dosage for longer term use. Also, to be able to use higher doses would have been a desirable therapeutic option nonetheless.
juniper88 wrote: Yes, "we" [the people reading this board] do not have much of a hint of proof of concent. Perhaps, patient #2 being on the treatment for 4 cycles could be considered a "hint". Either way, the investiigators might have hints that we simple do not know about. And these hints might have startted at lower doses than 300mg/m2. If I am right about patient #2 then a hint might have started at 60mg/m2. The concept of having to go to the highest possible dosage simply is not correct. And as Christian once told me, I understand the science just fine.