Avastin, gemzar & carboplatin

Anyone know experienced and know about the above chemo effectiveness? I had recurrence after 6 mths fr taxol & carboplatin. And I'm going thru 12 times chemo again of avastin etc. I'm pretty tired with this and always have the fear of recurrence. Any prevention such as in diet etc?

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I went through this regiment and it worked for awhile. I'm now on Topotecan. Watch your BP with the Avastin - mine went sky high. Recurrence is just a part of our lives I think. Don't worry about what you can't control and just keep on living. God Bless.

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I had recurrence 9 mos after Taxol/Carbo. Then, Gemzar/Carbo/Avastin brought me to NED and continuing Avastin maintenance gave me 18 mos before I recurred again. I think the only reason I recurred at that time was because my doc reduced my Avastin dose to less than 1/2. HOWEVER, we are all different. I DO think a lot of women have had success with this combo.

There has been a lot of discussion on here about diet and treatment by Naturopathic Doctors (NDs). A lot of women have been treated by NDs (in addition to traditional treatments) with success. In particular...see the current posting by Xericjean regarding her 10 year update.

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I also recurred 6 mo after carbo/taxol and am now on carbo/gemzar. My tumors have shrunk by 50% and one is gone. Seems to work for lots of gals.

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It doesn't surprise me having such early recurrences after Taxol use. Long-term survival Platinum + Taxol combinations remain disappointing at higher-dose levels. Conventional chemotherapy is given at high concentrations to force a drug or drug combination into poorly perfused areas of the tumor. The entire tumor is regarded as the target. This is not an ideal drug delivery, according to laboratory oncologists.

The goal is to maximize drug delivery to the drug-accessible target receptors and minimize drug deposition elsewhere in the body. The target is not the entire tumor, it is just that part of the tumor that drug(s) can easily and freely reach after escaping from the tumor blood vessels. Just enough drug (s) is given to bind to the drug-accessible target receptors and kill the drug-accessible tumor. Over a long enough period of time, the drug (s) will eventually get to all the malignant cells.

Tumors avidly seek their own blood supply via humoral factors. The discovery of VEGF lead to the approval of Avastin in some tumor types. It is a monoclonal antibody that binds and inactivates circulating VEGF in patients. However, there are no perfect drugs, there are simply drugs that work for certain patients. VEGF down-regulation is an attractive and highly appropriate therapy for a "subset" of cancer patients with many different diagnoses whose tumors use the VEGF pathway to their advantage.

Taxol has a cancer-promoting risk. It increases fivefold the production of Interleukin - 8 (IL-8), a cellular communication molecule that initiates the growth of new blood vessels to feed a growing cancer. IL-8 is under the control of an inflammatory regulating protein called nuclear factor-kappa Beta (NF-kB). When NF-kB is enhanced, it increases the production of IL-8, and thus Taxol fails to stop the growth of new blood vessels that feed a growing cancer, failing to prevent recurrence. And with Taxol promoting an increase of IL-8, how effective will it be with Avastin?

Adding Avastin, which only goes after VEGF-sensitive cancer cells, you need to go after other pro-angiogenic factors which can substitute for VEGF: FGF, PDGF, ephrin A1, angioprotein 1, IL-8, etc.

What is unique about the use (even though trial-and-error) of Gemzar + Platinum is "synergy," defined as supra-additivity wherein the whole is greater than the sum of the parts, reflects an elegant interaction between drugs predicated on their modes of action. While some synergistic interactions can be predicted based upon the pharmacology of the agents, others are more obscure.

The most probably mechanism for the synergy between Gemzar plus Platinum 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 the railroad company repairs damaged sections of rail track. Then the railroad company lays down new track. Platinum-resistant tumor cells do the same thing, and gemcitabine interferes with this process (Belpomme, et al. Gynecol. Oncol. 91:32-38, 2003).

Greg

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Greg...does Taxotere have the same problems as Taxol?...especially increasing the production of IL-8?

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Mimi

Taxotere (docetaxel) is another widely used taxane drug that is used in the treatment of cancers of the lung, breast, ovary and other common cancers. Despite the broad anti-tumor activity of taxanes, their clinical usefulness has been limited by common side effects such as painful nerve damage (neurotoxicity), reduction of white blood cell counts, liver damage, allergic reactions, nausea and vomiting, and other toxicities.

Taxotere is a synthetic version of Taxol. One difference is the absence of the Cremophor EL (castor oil) and the use of Polysorbate 80. Polysorbate 80 is used in pharmacology to assist in the delivery of chemotherapeutic agents across the blood-brain barrier. The product label for both drugs state they are highly lipophilic and insoluble in water. Side effects seem very similar. Taxotere is mostly (if not completely cross resistant with Taxol.

P-glycoprotein, or PGP is a transmembrane efflux pump. It pumps harmful things from the inside of the cell to the outside of the cell. In many cases, PGP is at least partially responsible for a patient's decreased sensitivity to taxane-based chemotherapy. As soon as the drug enters the cancer cells, the PGP pumps start pumping the drugs out. PGP effectively pumps the drug out of tumor cells before it has time to kill the cells.

In cell function analysis, Taxol has been found to be a drug with a below average probability of providing clinical benefit, based on the fact that taxanes are almost never synergistic with platinums, but only additive. Synergy is defined as supra-additivity wherein the whole is greater than the sum of the parts. It reflects an elegant interaction between drugs predicated on their modes of action. Cell function analysis has extensively examined the synergy between classes of drugs based on known modes of action.

Greg

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Greg...I am aware of most of the above, concerning both Taxol and Taxotere. It is the question of whether Taxotere also increases the production of IL-8. The PGP issue is something I had not heard of. Does it apply to both Taxol and Taxotere?
Thank you.

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https://www.youtube.com/watch?v=zeZFcIbwCZg

Very good information on diet.

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Both Taxol & Taxotere are taxanes and it applies to taxanes.

Taxane is a microtubule stabilising agent that destroys cancer cells by interfering with the cell cycle leading to apoptosis or cell death. Specifically, it interferes with the spindle microtubule dynamics within the cell that ensures the correct alignment of chromosome pairs before they pull apart and become segregated into two daughter cells. Similar to the strings on a puppet, microtubules need to be held at the correct tension for the chromosomes to align. Anything interfering with this process will ultimately cause cell death.

Taxane-treated cells have defects in mitotic spindle assembly, chromosome segregation, and cell division. Unlike other tubulin targeted drugs such as colchicine that inhibit microtubule assembly, however, Taxane stabilizes the microtubule polymer and protects it from disassembly. The inability of the chromosomes to achieve a metaphase spindle configuration leads to a mitotic block in which there is prolonged activation of the mitotic checkpoint with the subsequent triggering of apoptosis or slippage back into the G1-phase of the cell cycle without cell division.

The ability of a taxane to inhibit spindle function is generally attributed to its suppression of microtubule dynamics, but recent studies have demonstrated that suppression of dynamics occurs at concentrations lower than those needed to block mitosis. At the higher antimitotic concentrations, Taxane appears to act by suppressing microtubule detachment from centrosomes, a process normally activated during mitosis. The binding site for Taxane has been shown to reside on the beta-tubulin subunit.

In other words, Taxane gumms up the innards (microtubules) of all rapidly dividing cells (good cells and bad cells). When microtubules get gummed up, the tumor cell commits suicide. A report in the journal International Cancer Research stated that taxane drugs targets part of the cell cytoskeleton called the tubulin. Tubulin is used to build microtubules, which in turn make up the cell's structure. Destroying it kills the cell, but cancer cells eventually evolve mechanisms to pump out the drugs that do this (resistance). Resistance to anti-tubulin therapies, like Taxanes, is a huge problem in many cancers.

It's like a gasoline engine in an automobile. Say the motor is running and for some reason the key in the ignition is broken/jammed and you cannot shut the engine off, and you cannot open the bonnet to cut ignition wires to stop the engine. So the only other way is to pour sugar into the gasoline tank until the motor gummies up and stops running. Now, you shut off the engine the best way you possibly could because of the restrictions. However, while cutting ignition wires would save the engine for another day (replace just the wires), by placing sugar into the gas tank you virtually destroyed the engine, unless you can completely overhaul it.

Greg

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I was on a trial for Carbo/Taxotere with indefinite Avastin maintenance for nearly two and a half years, and I would say the combo did a good job keeping the cancer at bay, although I have now recurred (I only had a 9 months first remission from Carbo and Taxol alone). The Avastin side effects were minimal, and I didn't really get high blood pressure, although I am now taking a low dose beta blocker (but only because a study showed that women with oc who take certain beta blockers live far longer than those who don't). So I would say Avastin is a good drug if your body can tolerate it.

Now that I've recurred, I too am about to start Carbo and Gemzar, but in my case these will be combined with a new 'Avastin-like' trial drug (sorry, it only has a number, not a name). I've been listening to Greg about the synergy between Carbo and Gemzar, and my doctor thinks the new trial drug is very promising -- so this looks like a good option for me.

At the same time, I'm trying to step-up my complementary/alternative medicine so am off to a CAM retreat in Durango at the end of this month. I had previously 'modified' my diet but not changed it radically, and similarly had taken some supplements but not really tailored them to my particular needs -- so this is a new departure for me. In general, if you are looking at Naturopathic doctors, you need to find those who are FABNO certified (basically certified in naturopathic oncology). Here is a list:

http://www.oncanp.org/find_fabno.html

And, as mentioned earlier, Xericjean is a wonderful member to talk to about CAM medicine.

In the end, we all seem to respond individually to the various drugs and combinations so it's hard to predict which will work, but from what I've seen and learned over the past few years I think Avastin/Gemzar/Carbo is a logical choice after a shorter remission with Carbo/Taxol, and I wish you extremely well with it. Rose

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