The is similar to the principle achieved with functional profiling with Gemzar + Carboplatin.
The most probable mechanism for the "synergy" between Gemzar + Carboplatin is Gemzar inhibition of repair of platinum/DNA adducts. What this means is that platinum-resistant tumor cells "cut out" the damaged DNA (to which the platinum is attached) in the same way that a railroad company repairs damage sections of rail track. The railroad company lays down new track. Platinum-resistant tumor cells do the same thing, and Gemzar interferes with this process.
You want to administer the Gemzar first (to have it on board to inhibit the repair process). Then, you want to administer Carboplatin shortly thereafter. In addition, you don't want to give either Gemzar or Carboplatin by itself on any days of the cycle. This doesn't take advantage of the "synergy" between the drugs and, in many cases, will just increase toxicity.
If they can lower the dosage of Gemzar and not have that break after week three, the better. The "low-dose" protocol can have both anti-tumor and anti-vascular effects on various tumors, depending on the individual cancer patient.
Dr. Nagourney had found the availability of comparably mild agents, like the "low-dose" Gemzar + Platinum doublet, can be safely continued for long periods of time. He was the first to report that in the original PARP inhibitor clinical trial with Carboplatin + Gemzar, that even a lower starting dose (from 1000mg/ml2 to 800mg/ml2) resulted in significant toxicity and he suggested 600mg/ml2.
It's not the drugs per se, but rather how they are selected, that has changed outcomes so dramatically. This is about the biggest advantage of the functional profiling platform. The more they bring this out the more functional profiling shines.
http://cancerfocus.org/forum/showthread.php?t=3346