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Old 05-15-2012, 03:10 PM   #1
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Staggered Cancer Drug Delivery Better Than All In One Go

The fact that treating cancer patients with multiple drugs often results in better outcomes than a single drug treatment is long been known amongst the medical profession. However, a MIT study published in the May 11 issue of Cell has just demonstrated that the order and timing of administering drugs may also have a dramatic impact...

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Old 05-25-2012, 01:08 PM   #2
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Re: Staggered Cancer Drug Delivery Better Than All In One Go

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According to Yaffe, the concept of staggering drug treatments to achieve a maximum impact could be applied across a broad range of therapies. The team discovered similar boosts in tumor killing by pre-treating HER2-positive breast cancer cells with a HER2 inhibitor, followed by a DNA-damaging drug, and also observed good results with erlotinib and doxorubicin in some types of lung cancer.

Lee states:


"The drugs are going to be different for each cancer case, but the concept that time-staggered inhibition will be a strong determinant of efficacy has been universally true. It's just a matter of finding the right combinations."
....................................
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Old 05-26-2012, 02:57 AM   #3
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Re: Staggered Cancer Drug Delivery Better Than All In One Go

Role on when they do! At present it seems a one size fits all!
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Old 05-26-2012, 12:12 PM   #4
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Re: Staggered Cancer Drug Delivery Better Than All In One Go

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
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Old 05-27-2012, 07:20 PM   #5
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Re: Staggered Cancer Drug Delivery Better Than All In One Go

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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.
How long is shortly?
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Old 05-27-2012, 07:53 PM   #6
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Re: Staggered Cancer Drug Delivery Better Than All In One Go

Being that you don't want to give either Gemzar or Carboplatin by itself on any days of the cycle, that would mean shortly thereafter on the same day, to take advantage of the synergy between the drugs, without increasing toxicity.
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Old 05-27-2012, 07:56 PM   #7
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Re: Staggered Cancer Drug Delivery Better Than All In One Go

Therefore.."How long is shortly?"
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Old 05-27-2012, 08:05 PM   #8
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Re: Staggered Cancer Drug Delivery Better Than All In One Go

Within that clinical visit.
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Old 05-27-2012, 08:47 PM   #9
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Re: Staggered Cancer Drug Delivery Better Than All In One Go

So...translating to real world..morning infusion followed by afteernoon infusion of secondary?
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Old 05-27-2012, 08:54 PM   #10
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Re: Staggered Cancer Drug Delivery Better Than All In One Go

Whatever would knock your socks off!
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Old 05-27-2012, 08:56 PM   #11
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Re: Staggered Cancer Drug Delivery Better Than All In One Go

Only thing that knocks my socks off are strategies prone to working.
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Old 05-27-2012, 09:00 PM   #12
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Re: Staggered Cancer Drug Delivery Better Than All In One Go

You can always rely on the trial-and-error physician's choice strategy. Best guesstimate.
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Old 05-27-2012, 09:03 PM   #13
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Re: Staggered Cancer Drug Delivery Better Than All In One Go

Cop out response, Greg.

What's the interval in the estimation you promote?
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Old 05-27-2012, 09:09 PM   #14
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Re: Staggered Cancer Drug Delivery Better Than All In One Go

I'll repeat it once more. Being that you don't want to give either Gemzar or Carboplatin by itself on any days of the cycle, that would mean shortly thereafter on the same day, to take advantage of the synergy between the drugs, without increasing toxicity.
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Old 05-27-2012, 09:15 PM   #15
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Re: Staggered Cancer Drug Delivery Better Than All In One Go

Same day? What portion of the 24hr schedule?

Sorry..can't promote Devil in the details while remaining vague. I have VERY strong interest in Chronotherapy(Levi, Hruschesky)..unfortunately the tools seem admittedly crude at this stage.
Meaning...details matter outside Oca and Gemzar. Especially in terms of obtainable infusion schedules...some being obtainable by gross replicative standard style infusion approaches..or..via limited availability chronometric/programmatic infusion via clinics with programmable pumps like at Block center.
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Old 05-28-2012, 11:42 AM   #16
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Re: Staggered Cancer Drug Delivery Better Than All In One Go

Rich

I'm not a chemotherapist. I don't know (or remember anymore) the intimate details of when the gas station serves business during the day. All I can tell you (a.k.a. the Gemzar + Carboplatin protocol) is that it suggests shortly after on the same day.

Yes, I do know about the "circadian" issue being talked a lot in medical oncology, and the circadian biology applying timing for effective administration of medicines (biological temporal rhythms), called chronobiology.

Greg
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