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Ovarian cancer and brain metastases

gdpawel's picture
gdpawel
Posts: 549
Joined: May 2001

The mechanisms by which primary tumors produce brain metastases is thought to be hematogenous (blood) spread from primary or secondary sites in the lung. Since the brain has no lymphatic system, all tumors metastasizing to the brain do so by spreading through the bloodstream. Arterial blood passes through the lungs before entering the brain, and collects tumor cells filtered out in capillaries, which subsequently embolize to the brain.

The jury is out on how ovarian cancer spreads. As less is known about this disease than other cancers this has not been definitively answered and there is controversy among the ranks of researchers and clinicians. Many believe it does not spread via the lymph and spreads through cells shedding into ascites in the absominal cavity and then seeding in distant sites. It does spread this way but is probably not the only way as it is found in lymph nodes as well.

There are essentially four ways that ovarian cancer metastasis takes place.

1. The first has to do with direct contact with the tumor itself. The tumor invades nearby organs, such as the uterus, bladder, or fallopian tubes.

2. Ovarian cancer can spread by what is known as seeding. This is shedding cancer cells into the abdominal cavity. These cells can then attach to the liver, colon, or stomach and begin to proliferate. This scattering process can make it possible to infect several different key organs.

3. Ovarian cancer metastasis can involve portions of the tumor breaking off and invading the lymphatic system. The collections of cancerous cells are then transported to distant organs, such as the lungs, where new tumors form and grow.

4. Ovarian cancer cells can travel through the bloodstream to other areas of the body, where they develop into various types of cancer.

It has long been believed that it does not metastasize to the brain - however in recent years - women living longer are developing brain mets. One school of thought believes that platinum and taxane drugs maybe weakening the blood brain barrier but that does not explain every instance.

Ovarian cancer uncommonly involves the central nervous system. Brain metastasis were a rare complication of ovarian cancer with only 67 well-documented cases in medical literature until 1994, according to the National Cancer Institute. A multi-institutional study of 4027 ovarian cancer patients over 30 years identified only 32 cases while an autopsy study of ovarian cancer reported an incidence of 0.9%. Even more rare was the occurrance of Leptomeningeal Carcinomatous or Carcinomatous Meningitis. Until 1994, there have been only 14 cases reported. This presentation is similar to metastases from other solid tumors (breast, lung).

In a study by Christos Kosmas, M.D., consultant medical oncologist, Department of Medicine and Medical Oncology Unit at Helena-Venizelou Hospital, Athens, Greece entitled, "Carcinomatous Meningitis: Taxane-Induced," which found what is called "dissemination after taxane-based (Taxol) chemotherapy." The study conclusions stated that Carcinomatous Meningitis (a CNS metastasis) after a major response to front-line taxane-based regimens represents a grave disease manifestation and its incidence appears increased when compared retrospectively to non-taxane-treated patients http://cancerfocus.org/forum/showthread.php?t=2871

During the past fifteen years it has been frequently observed that more and more patients were presenting central nervous system (CNS) involvement as the only evidence of disease progression. It seems that retrospective studies in patients with epithelial ovarian cancer do not differ among patients who relapsed with isolated brain metastases and those with relapse outside the CNS.

The trafficking of cancer cells to their final destination may be guided by factors produced by stromal cells of their host organ. For example, Melanoma cells are closely related to CNS cells. Breast cancer cells more commonly are found in the posterior pituitary. Renal, gastrointestinal and pelvic are cancers tend to metastasize to the cerebellum.

Brain metastases, unfortunately are very common and grave condition in the natural history of patients with cancer. It is estimated that approximately 250,000 patients with cancer will develop brain metastasis in the United States each year. Autopsy data have shown that up to 50% of patients who die with cancer have evidence of spread to the central nervous system, with approximately 40% of these patients having a solitary or single metastasis.

Solitary means that this metastasis is the only evidence of cancer in the whole body, whereas single means that there are other deposits of cancer outside the brain. Tumors more prone to brain dissemination are Lung, Breast, Melanoma, Renal Cell Carcinoma, Colorectal and Sarcoma.

Metastases are defined as the appearance of neoplasms in parts of the body remote from the site of the primary tumor. Metastasis can occur through one of three processes: direct seeding of body cavities or surfaces, lymphatic spread, and hematogenous spread.

Distant metastasis via the bloodstream may affect virtually any organ. The lungs, bones, liver, and adrenals are the most common of metastasis. In order for metastasis to occur, tumor cells must break free from the primary mass, enter the lymphatics or bloodstream, and produce a secondary growth at a distant site.

Although millions of cells are released into the circulation each day from a one primary tumor, few actually survive. Factors determining the success of metastasis include surface attachment, hormones, blood supply, and the body's own immunity.

Approximately 30% of intracranial tumors are metastases. The most common primary sites for these metastases are the lung, breast, skin, kidney, and gastrointestinal tract. Carcinomatous meningitis, a condition resulting in widespread dissemination of carcinoma in the meninges, is particularly associated with small cell carcinoma of the lung, adenocarcinoma of the lung, and carcinoma of the breast.

It doesn't mention anything about ovarian cancer. I was shocked to find out the studies about Taxol!

An article in Gynecologic Oncology (Volume 92, Issue 3, March 2004, Pages 978-980) by John P. Micha, et al, Gynecologic Oncology Associates, Hoag Memorial Hospital Cancer Center, Newport Beach, CA states that brain metastases resulting from primary ovarian cancer are rare, however, there have been recent studies suggesting an increased incidence of brain metastases (PubMed PMID: 14984970).

Am J Clin Oncol. 2010 Oct 1.

Multidrug Resistance Gene (MDR-1) and Risk of Brain Metastasis in Epithelial Ovarian, Fallopian Tube, and Peritoneal Cancer.

Matsuo K, Eno ML, Ahn EH, Shahzad MM, Im DD, Rosenshein NB, Sood AK.

Abstract

BACKGROUND: To evaluate risk factors that predict brain metastasis in epithelial ovarian, fallopian tube, and peritoneal cancer.

METHODS: All patients with FIGO stage I to IV who underwent initial cytoreductive surgery between January 1995 and January 2009 were evaluated. The tumor samples were evaluated for 7 markers including multidrug resistance gene (MDR-1), DNA aneuploidity and S-phase fraction, human epidermal growth factor receptor 2, estrogen receptor, progesterone receptor, p53 mutation, epidermal growth factor receptor, and CD31. Biomarker expression was evaluated as a predictor of hematogenous metastasis to the following locations: (i) liver and spleen, (ii) lung, and (iii) brain.

RESULTS: There were 309 cases identified during the period. Of those, 5 (1.6%, 95% CI: 0.2%-3.0%) women developed brain metastasis. Time to onset of brain metastasis was significantly longer than that for other recurrent sites (median time to recurrence after initial cytoreduction, brain vs. lung vs. liver, 21.4 vs. 12.6 vs. 11.0 months, P < 0.05). Significantly increased expression of MDR-1 was seen in tumors from women who developed brain metastasis (brain vs. nonbrain sites, 80% vs. 4.2%-24.3%, P = 0.004). In multivariate analysis, MDR-1 was the only significant variable associated with the risk of brain metastasis. MDR-1 expression predicted brain metastasis (receiver-operator-characteristic curve analysis, AUC 0.808, P = 0.018), and with a 10% positive expression of MDR-1 as the cutoff value, sensitivity, specificity, positive predictive value, negative predictive value, accuracy of prediction of brain metastasis were 80%, 86.1%, 15.4%, 99.3%, and 85.9%, respectively (odds ratio: 24.7, 95% CI: 2.64-232, P = 0.002).

CONCLUSIONS: Increased expression of MDR-1 in the tumor tissue obtained at initial cytoreduction is associated with increased risk of developing brain metastases in women with epithelial ovarian, fallopian tube, or peritoneal cancer.

http://www.ncbi.nlm.nih.gov/pubmed/20921883

gdpawel's picture
gdpawel
Posts: 549
Joined: May 2001

Brain metastases commonly develop among patients with ovarian cancer, and do so rapidly in those with advanced disease, a retrospective review found.

In a study of 78 women with ovarian cancer who developed one or more brain metastases, 50% developed a single metastasis, according to Sewit Teckie, MD, and colleagues from Memorial Sloan-Kettering Cancer Center in New York.

In addition to that group, another 19% of patients were found to have two or three metastases on initial diagnosis, 23% had four or more, and 8% already had leptomeningeal disease, Teckie told MedPage Today during a poster session at the annual meeting of the American Society for Radiation Oncology (ASTRO).

The patients were treated at the cancer center between 1983 and 2010. Their median age was 54.8 and 88% had stage III/IV disease.

The location of the metastases was the cerebral hemisphere in 56%, the cerebellum in 15%, and both in 28%.

Median overall survival was 62.3 months (95% CI 51.2 to 73.3).

The median time after diagnosis to the detection of brain metastasis was 71.1 months in patients with early-stage disease and 38.3 months when disease was diagnosed at stage III/IV.

Median follow-up for the entire cohort was eight months, and for the six patients still alive at the time of this analysis, median follow-up was 15 months.

Among all patients who developed the metastases, median subsequent survival was 8.9 months (95% CI 5.5 to 15.3), with a median survival of 14 months (95% CI 7.7 to 27.9) specifically in those who had only one metastasis.

A total of 92% of patients received whole- or partial-brain radiation therapy or stereotactic radiosurgery for their metastatic disease, while 49% had surgical treatment.

Most of those who had surgery had only one brain metastasis.

A total of 25 patients who underwent surgery also had postoperative radiation, and 15 required salvage radiation after local treatment was unsuccessful.

On multivariate analysis, these factors were associated with poor survival:

Karnofsky performance status ≥70, HR 0.35 (P=0.004)
Uncontrolled primary tumor, HR 1.81 (P=0.03)
Four or more brain metastases, HR 2.73 (P=0.002)
Leptomeningeal disease, HR 3.34 (P=0.01)

Among 33 of 39 patients for whom follow-up imaging was available, progressive or recurrent metastatic disease had occurred and 20.5% had developed leptomeningeal disease.

Six of those patients had an initial partial or complete response to radiotherapy, but two had later recurrences.

Median survival after radiation therapy for leptomeningeal disease was four months, although one patient remained alive after one year.

"More cases of leptomeningeal disease are being reported. These patients did better than patients usually do," Teckie said. "We knew leptomeningeal disease was a poor predictor, but this has not previously been analyzed statistically," she added.

In general, although brain metastases occur earlier in advanced ovarian cancer, if only one metastasis is present, stereotactic radiosurgery or surgery plus radiation therapy can provide a durable response and improve survival for some patients, she concluded.

Primary source: American Society for Radiation Oncology ASTRO 2011; Abstract 2568.

Source reference: Teckie S, et al "Predictors of survival in ovarian cancer brain metastases" ASTRO 2011; Abstract 2568.

gdpawel's picture
gdpawel
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Joined: May 2001

In stem cell research, anti-cancer treatments often effectively shrink the size of tumors, but some might have the opposite effect, actually expanding the small population of cancer stem cells that then are capable of metastasizing.

Using the CellSearch System technique that quantifies circulating tumor cells, scientists had shown that chemotherapy with Taxol causes a massive release of cells into the circulation, while at the same time reducing the size of the tumor, explaining that complete pathologic responses (tumor shrinkage) do not correlate well with improvements in survival.

Circulating tumor cells (CTCs) are cancer cells that have detached from solid tumors and entered the blood stream. This can begin the process of metastasis, the most life-threatening aspect of cancer. To metastasize, or spread cancer to other sites in the body, CTCs travel through the blood and can take root in another tissue or organ.

Even before the advent of the CellSearch technique, which was the "holy cow" moment about the dissemination after taxane-based chemotherapy, it had been observed in various cell-death assays, that there was an increase in the number of metabolic activity of mitochondria of the surviving cells from taxane therapy, even in cases where the majority of the cells are being killed by taxanes.

It may indeed give clincial response (tumor shrinkage), sometimes impressive, however, these are mostly short-lived and relapses after a response to taxanes are often dramatic.

Taxol actually causes cancer cell microtentacles (or extensions of the plasma membrane of cancer clles) to grow longer and allows tumor cells to reattach faster, appear to play a key role in how cancers spread to distant locations in the body.

leesag's picture
leesag
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I'm not big on research and stats. (I'm not impugning your knowledge or your experience,I'm so sorry for the loss you experienced and I'm grateful for your knowledge and the fact that you share it with all of us. I just feel that it's important to provide a little personal perspective and hope).

When I was diagnosed with brain mets, after being in remission for all of us 9 months, I was devastated. My neurosurgeon and radiation oncologist at University of Maryland gave me a great deal of hope, however. I was informed that I had three lesions. The largest of the three was removed with surgery, the others were shrunk with whole brain radiation and then eradicated with Gamma Knife. I am currently cancer free. My doctors have told me that there is very little chance (10%) that my cancer will return in the brain again. I'm liking those odds and planning to stick around for a few more decades.

:)

Leesa

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gdpawel
Posts: 549
Joined: May 2001

Leesa

I sincerely appreciate your personal experience. Aside from research and stats, here is a little personal perspective from the other side. When my wife was diagnosed with a solitary brain met, 11 months after receiving Taxol + Carboplatin treatment, the 3.5cm tumor was excised and she received 5 fractions (1000 cGy) of focal radiation to the local tumor bed, plus 20 fractions (4000 cGy) of whole brain radiation over a 35 day period.

Recurrence of the cerebral metastasis was observed 21 months afterwards, with 4 mm-sized metastatic tumors in and around the previously resected and radiated cerebeller tumor. Because of her weakened condition from whole brain radiation, Gamma-Knife treatment was the best treatment option (although she did not survive much after it). With a very little chance (10%) of cancer returning in the brain again, I'm not big on statistics either. So much for whole brain radiation. Best wishes!

Greg

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leesag
Posts: 624
Joined: Jan 2010

Hi Greg,

I understand your perspective entirely, words cannot express how sorry I am for your loss. This cancer is so unfair and unpredictable. I truly appreciate everything you post to help OVCA patients and their families.

Hugs and prayers,

Leesa

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Tethys41
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Double post. Read the next one.

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Tethys41
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So, this comment will likely fly in the face of the medical perspective, but if one accepts that cancer is a systemic disease and not a disease of the organs, then it would seem that altering the terrain of the body would reduce the likelihood that cancer cells released into the blood stream from Taxol treatment would grow elsewhere in the body. I personally know people with tumors in their bodies, who keep them controlled with a specific type of diet, exercise, stress management, supplements, etc. If they can keep a full-sized tumor at bay, I would think the same practices would neutralize the ciruculating tumor cells released by Taxol.

leesag's picture
leesag
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Are you also controlling your tumors with diet, exercise, stress management and supplements?

So far, I've found medical science, surgery and other medical interventions to be successful.

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Tethys41
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Leesa,
I am currently NED, but am practicing the same lifestyle guidelines as those who do control their tumors, in order to stay NED as long as possible.

leesag's picture
leesag
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Congratulations on being NED! May you continue to enjoy the dance for the next several decades (at least a half dozen!) I, too, am NED at the moment-thanks to my Gyn/Onc's surgery, my Med/Onc's chemo, my Neurosurgeon's brain surgery, and my Radiation/Onc's wbr, and Gamma Knife.

And lest I forget, my faith that God has a plan for me and my job isn't done by a long shot!

:) Through it all, I drank red wine and ate chocolate without regret or apologies! ;)

Cheers!

Leesa

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Hissy_Fitz
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I have been NED officially for 19 months - probably NED for a couple of additional months. I would be really, really pissed if I gave up alcohol, sugar, dairy, red meat and God knows what else, only to recur anyway. So I've decided not to take the chance.

Carlene

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Tethys41
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Joined: Sep 2010

Leesa, I have kept up with the posts related to your journey and I hold you in very high esteem. I think we all need to do whatever we are most comfortable doing. That doesn't make any of us wrong. I am so happy that your treatments and surgeries have done you well, and deeply hope they continue to do so.

Carlene, I had to laugh when I read your response because I think in just the opposite way. If I had a recurrance and had not changed my diet and lifestyle, I'd be kicking myself, thinking that if I had only done something more, maybe I would have prevented it. I feel that the changes I've made are one's I really knew I should have made before my diagnosis, but never had the motivation. I won't kid you, it was a bit challenging kicking the sugar and gluten habit. But now, I don't miss them at all.

Stay healthy

leesag's picture
leesag
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Joined: Jan 2010

double post

california_artist
Posts: 850
Joined: Jan 2009

as a result of Taxol use there is greater likelihood that a cancer will met to the brain?

Could you please post these two threads on the uterine board as our scans are usually "eyes to thighs"?

Thank you,

Claudia

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LaundryQueen
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Joined: Mar 2011

When I was in the ER last year with a bizarre brain reaction (staggering, stammering, blurred vision & unequal pupils), they fast-tracked me for a brain CT suspecting mets to my brain. Thankfully, the scan was negative but I was too shell shocked to refuse the taxol after that.

After the SECOND visit to the ER for the SAME symptoms, the doctor finally stopped giving me Taxol. I have to admit that I had a dramatic reduction in the tumor burden from the Taxol but couldn't convince the doctor to just decrease the dose.

I think some women are followed up with prolonged Taxol therapy as some oncologists understand the way Taxol disseminates tumor cells throughout the body. I think some women have a strong enough immune system to clean up after Taxol while others are not so fortunate.

What bothers me a lot is how second-line & subsequent chemos are chosen without any attempt at determining chemosensitivity for most of us. The attitude is "Let's see if this works and if it doesn't, we'll try something else as long as your bone marrow holds up." Ugh!

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Hissy_Fitz
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I'm a poster child for Taxol. I did 18 infusions of the stuff and tolerated it extremely well.

It is strong bug juice, for sure, but I agree...it doesn't agree with everyone and your doctors should have figured that out after the first ER visit.

Carlene

clynn13
Posts: 21
Joined: Sep 2010

Well, so far I have no brain mets and all together I have has over 50 taxol infusions. Most of them were on the low dose schedule.

gdpawel's picture
gdpawel
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Dr. Nagourney is medical and laboratory director at Rational Therapeutics, Inc., in Long Beach, California, and an instructor of Pharmacology at the University of California, Irvine School of Medicine. He is board-certified in Internal Medicine, Medical Oncology and Hematology. He blogged recently about the so-called "standard" treatment for ovarian cancer:

"I watched with interest as the GOG 182 five-arm clinical trial unfolded. This international study of over 4,000 patients randomly mixed and matched drug combinations but provided no evidence of superiority of one arm over another. The final conclusion of the manuscript that reported these results (Bookman, MA., Brady, MF, McGuire, WP, et al. J Clin Oncol 27: 1419-1425, 2009), stipulated that carboplatin plus taxol remained the “gold standard” for advanced epithelial ovarian carcinoma. A study of over 900 patients that compared carboplatin plus gemcitabine to carboplatin plus paclitaxel induction (Gordon A, Teneriello M, Lim, P, et al Clinical Ovarian Cancer, 2, 2:99-105, 2009) again provided comparable outcomes between arms yet carboplatin plus taxol remains the “gold standard.”

To this collection of published experiences, we now add the report by Sandro Pignata and co-investigators from the MITO-2 Phase III trial (Pignata, S., Scambia, G., Ferrandina, G., et al. J Clin Oncol 29: 3628-3635, 2011). This clinical trial conducted by Italian investigators compared carboplatin plus taxol to carboplatin plus pegylated liposomal doxorubicin (PLD) known in the U.S. as Doxil. Four hundred and ten patients were randomized to each arm of the trial. The results revealed numerical superiority for the carboplatin plus PLD arm in terms of median progression-free survival (19 months vs. 16.8 months) and numerical superiority for overall survival for the carboplatin plus PLD over the carboplatin plus taxol arm (61.6 vs. 53.2 months). However, these results did not achieve statistical significance. Therefore, the authors conclude that carboplatin plus taxol “remains the standard first-line chemotherapy for ovarian cancer.” While they do grant that, based on toxicity, carboplatin plus PLD could be considered as an alternative therapy.

With the GOG 182 study, the Gordon study (comparing carboplatin plus gemcitabine) and the most recent Pignata study comparing carboplatin plus PLD all establishing activity for several first-line regimens, why is it that the gynecologic oncologists continually return to carboplatin plus taxol as the “gold standard?”

Is there not ample evidence that several regimens provide similar results and survivals? Is there not evidence that the toxicities differ? Why can’t the gynecologic oncologists get off the dime? Why can’t they admit that several treatment regimens are appropriate and indicated for the malignancy? Why can’t they admit that some patients may, in fact, do better with one treatment over another?

I may add, it’s never been shown that adding paclitaxel (Taxol) to first line treatment of ovarian cancer improved survival. It’s been shown that paclitaxel + platinum is superior to paclitaxel + cyclophosphamide. It’s never been shown that paclitaxel + platinum is superior to single agent cisplatin or carboplatin.

The findings in the GOG 132 study and the International Collaborative Ovarian Neoplasm study (ICON3) of equivalent effectiveness with the initial use of single-agent platin compared with platin-taxane doublets, the issue of whether the combination of platin and paclitaxel is superior to initial single-agent platin is still unresolved. First-line comparative studies have demonstrated equivalent effectiveness.

Muggia FM, Braly PS, Brady MF, et al: Phase III randomized study of cisplatin versus paclitaxel versus cisplatin and paclitaxel in patients with suboptimal stage III or IV ovarian cancer: A Gynecologic Oncology Group study. J Clin Oncol 18:106-115, 2000

The International Collaborative Ovarian Neoplasm (ICON) Group: Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: The ICON3 randomised trial. Lancet 360:505-515, 2002

Source: JCO, Vol 27, No. 9, March 20, 2009

evertheoptimist
Posts: 140
Joined: Jan 2011

greg,

there is indirect evidence that Taxol does have additive value to single agent carboplatin.

The Japanese dose dense regiment yield an amazing PFS and OS benefit. Note that the scheduling changes were done for TAXOL only. Carbo was still administered on a 3 week schedule. This is an indirect evidence that taxol does something, and when an optimum schedule was used for taxol infusion, the patients benefited greatly. If taxol played no role, chancing taxol administration would not have yield any improvement.

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gdpawel
Posts: 549
Joined: May 2001

ETO

Sometimes drug "combinations" have merely an "additive" anti-tumor effect and do not produce a "synergistic" (cooperative) effect. Additive is where the whole equals the sum of its parts. Synergy is defined as supra-additivity wherein the whole is greater than the sum of the parts, which reflects an elegant interaction between drugs predicated on their modes of action.

You'd want a drug combination to produce a synergistic effect and not merely an additive anti-tumor effect, or resistant to an "individual's" tumor cells. You really want to take advantage of the synergy between "effective" drug combinations.

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.

Clinical oncologists using cell-based assays have found out that the combination of Gemzar + Platinum (either Cisplatin, Carboplatin or Oxaliplatin) is about the most important drug "combination" introduced for the treatment of solid tumors in the past twenty years. Clinical responses to real-time assay analysis with this regimen are unprecedented.

Cell culture assays had contributed, in terms of recognizing the synergistic effects of this combination, in getting clinical trials with this regimen started in a broad spectrum of cancers, including ovarian.

evertheoptimist
Posts: 140
Joined: Jan 2011

ah... greg,

you can't have it both ways. You stated above that taxol has hardly any added benefit to carbo, not even additive value. Now, you are saying, it has additive value, but still not good enough since it does not have synergistic value. I am not challenging you with the additive vs. synergistic. I was simply providing a different perspective to your statement earlier that taxol does not add much benefit.

The dose dense study produced amazingly significant outcome (PFS difference of 11 months!!!! - this is the best outcome I have EVER seen in all the studies I read so far), and that amazing PFS difference was SOLELY attributed to the variation in Taxol drug delivery schedule. If Taxol had not had such an important role in this regimen, tinkering with its delivery schedule should NOT have produced this kind of unprecedented study outcome. People can say all they want about Taxol' lack of effectivess. However, until somebody comes up with an alternative explanation of how this clinical study outcome could have happened while discounting the singular role of Taxol in this case, I will have hard time believing the argument.

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gdpawel
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Not going to split hairs here. You want a drug combination to produce a synergistic effect and not merely an additive effect. You want to take advantage of the "synergy" (cooperation) between "effective" drug combinations. Taxanes are almost never synergistic with platinums. What makes Gemzar + Platinum so successful is the synergistic effects of this combination.

The dose-dense protocol gives the drug more often, but not at a "lower" dose. Dose-dense chemotherapy shortens the treatment cycle while maintaining roughly the same chemotherapy dosage as conventional chemotherapy (the process reduction of time gap between two regular doses).

Dose-dense treatment is usually given with breaks of several weeks between doses to let the body try to recover. However, the anti-angiogenic effects of dose-dense therapy is masked and marginalized by administering it this way.

Low-dose chemotherapy not only shortens the treatment cycle but "lowers" the dosage of treatment a patient can withstand during shorten administration of "any" conventional drugs.

The main targets of dose-dense chemotherapy are proliferating tumor cells. The main targets of low-dose chemotherapy are the endothelial cells of the growing vasculature of a tumor. In other words (any) chemotherapeutics can be used as anti-angiogenic agents.

Blood vessel cells are less likely than tumor cells to become resistant to chemotherapy, so if cancer cells become drug resistant, these drugs should still be able to shrink tumors by destroying their blood supply.

Since the endothelial cells (involved in angiogenesis) are the first in the tumor to undergo cell death (apoptosis), the more frequent, and lower-dose therapy can have an impressive anti-angiogenic and anti-tumor effects.

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Tethys41
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Joined: Sep 2010

Ever,
I can't speak for everyone here, but I deeply appreciate the information Greg regularly posts here. Just as with the information my doctor shares with me, if I have a question regarding Greg's information, I will ask him about it. If I'm still not comfortable with it, I will do further research. I have seen your posts over on the Uterine cancer board. I spent a few short weeks posting over there until the confrontational, "I'm right/you're wrong" attitude discouraged me from continuing to visit over there. Not saying you're one oof them. As with any member here on the Ovarian cancer board, feel free to ask questions, but please do not make this into an all or nothing debate. People on the Uterine board miss out on a lot of beneficial information that is out there because a few members are contrary and combative. Please do not discourage our helpful resources on this board.

evertheoptimist
Posts: 140
Joined: Jan 2011

tethy,

If anything, on the uterine board, I posted a reply defending Greg when some snarky posters asked him why he is posting all this, to inform us or scare us. I have done that in other boards too where greg provides a lot of information and some odious posters came up with unpleasant responses to his posts. I do believe he is a very valuable source. I correspond with him and collaborate with him in many interesting discussion threads.

I believe my reply was measured and reasoned and added value to this discussion. The fact that I challenged some of statements should NOT be regarded as shutting him up. As long as discussion is civil and based on logic, chastising posters for challenging other's claim is just as bad as coming up with snarky, dismissive replies. He was going in the direction of dismissing taxol as a meaningful therapeutic agent, and I challenged that with a very well grounded logic. I think I enriched the discussion by pointing out the potential that Taxol has a valid position as a therapeutic agent.

Just as you mentioned in your post, please do not discourage people from sharing thoughtful and well laid out logic. If I had used uncivil language and unfounded logic, you would have every right to censure me. Since this is NOT the case, you should not assume the position to discourage people from contributing their well thought out opinions. when this type of censorship proliferates, it lowers the quality of discussion.

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gdpawel
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Joined: May 2001

There is nothing really wrong with a little bantering tone in discussion forums. The playful and friendly exchange of teasing remarks. They are not takened seriously. It is all in the art of forensics, debating, speech and argumentation. I learn just as much (if not more) from thought-provoking questions on boards. You'd be surprised how much you can pick up. There is nothing wrong with being challenged.

Major health care issues are discussed on blogs and discussion boards more extensively than they could ever be discussed in academic articles. The ability of readers to leave comments in an interactive format is probably the most important part of most blogs and discussion boards. The interactive format allows rapid responses to medical and health care issues which provides valuable feedback and commentary not available through traditional media.

There is one thing that really annoys me on the CSN board, that is the software program. I see what "slow as molasses in january" means! It has a lot to be desired.

california_artist
Posts: 850
Joined: Jan 2009

I am from NYC originally, and the most fun one could have was a lively opinionated discussion in a coffee place in the Village, among friends, sometimes people at a neighboring table would chime in with their thoughts too. Things would get loud as people were passionate, there could even be such high brow comments as “your mother,” but in the end we all hugged with a see you tomorrow. so I just love the give and take on these boards, and never understand when defensiveness sneaks in, although there was one time when I did get all huffy and puffy, which I regret tremendously, as that is not my way. I am in fact an incredibly friendly, funny, joke making sort who loves an intellectual discussion. I have learned so much from all of you. So, to all of you, I'm all for more of the same. Hope we keep having fun and learning all we can from each other. The more we know, the more rational the decision we can make.

Love and hugs to go around, : ~ )- and yes, I did make a stupid smiley face. Good Grief!

claudia

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daisy366
Posts: 1493
Joined: Mar 2009

Greg, I am happy to read that you are open to discussion and not easily offended. I am there with you - to discuss and learn - and question. Questions are good because that's how we learn and give deeper meaning to things.

I'm sorry, optimist, that you took my response as snarky (I love that word). I try not to be. I wanted more information, is all. Life is too short and precious. I agree with Claudia and Greg, that we should continue on with civil conversation, unafraid.

My best to all here, Mary Ann

JoAnnDK
Posts: 276
Joined: Jun 2011

I loved your post! You are too funny. I too would be really pissed if I gave all that stuff up for naught.

I have cut back on red meat (a long time ago) and meat in general now, but still eat it. And pasta and rice. After all, the anti-inflamation diets all "allow" fish and whole grains. I just add a bit to that.....an occasional dessert and definitely wine.

JoAnn

JoAnnDK
Posts: 276
Joined: Jun 2011

Is it "snarky" to post something that offers a correction to something else that was posted? For example, if I posted that "red meat is good for cancer patients" and someone corrected me, would that be "snarky" ????

At any rate, go ahead and consider this snarky or helpful...it is everyone's choice. This is a post of mine from the uterine cancer board where I wrote:

MedPage Today

Greg, MedPageToday should be ashamed of itself for this headline:

ASTRO: Brain Metastases Common in Ovarian Cancer

.....when this is not true at all and was extrapolated from ONE abstract of an article that has not yet even been peer-reviewed OR published in a medical journal.

This was one study of 78 women ---- conducted over 27 years. How many cases of ovarian cancer were seen at Sloan Kettering in those 27 years? I would bet it was thousands, yet this so-called study focused on 78.

So the headline should rightly say "Brain Metastases Common in 78 Ovarian Cancer Patients in 27 years". But this would not have garnered nearly as much attention, would it?

I have long noticed this tendency of MedPage to sensationalize in its headlines. Shame on them.

Here is a similar study done by/at MD Anderson which is NOT misleading because it states the number of patients there over the years who had ovarian cancer (8,225) versus the number studied (72).

http://www.ncbi.nlm.nih.gov/pubmed/15015663

This is even more accurate: http://theoncologist.alphamedpress.org/content/11/3/252.full

Background. Brain metastases from epithelial ovarian cancer (EOC) are rare. This report is based on a review of the literature.

Brain metastases in ovarian cancer are RARE (not common)......emphasis mine.

I was a researcher for a long time and always remember a class I had in college....subtitled "How to Lie With Statistics". One has to be so careful to check out all these sensationalist articles for validity.

JoAnn

LaundryQueen's picture
LaundryQueen
Posts: 682
Joined: Mar 2011

Ugh! If you are going to be that way about statistics, JoAnn, then how can you trust ANY research? I agree with you about how data can be manipulated--there is a lot of data being "massaged" every day. I think it's important to sift thru as much information as one can and make the best informed decision possible.

I believe that there is an art to practicing medicine as well as a science--I think less than 50% of what is practiced is evidence based. There's an expression that goes something like this: Change happens in medicine one funeral at a time (the funeral is in reference to the death of the physician rather than the patient). In 100 years, the treatment of cancer will be very different that it is today of that I feel certain.

JoAnnDK
Posts: 276
Joined: Jun 2011

Yes, I can trust research, but ONE study, misrepresented by MedPage Today, is not one I will believe in.

Like you, I believe in sifting through information. One has to look at the information, the source, etc. I am so disappointed in MedPage Today.....like I said, they should be ashamed. That headline is so deceiving. But then again, if one looks at googled results and trusts everything one sees, many of those results are deceptive.

gdpawel's picture
gdpawel
Posts: 549
Joined: May 2001

I've been following the taxane dissemination and brain metastasis reasearch for ten years, ever since I discovered cell function analysis in 2001. Every once in awhile more and more data come out. It's just that the data hits across various tumor types. http://cancerfocus.org/forum/showthread.php?t=2871

An article in Gynecologic Oncology (Volume 92, Issue 3, March 2004, Pages 978-980) by John P. Micha, et al, Gynecologic Oncology Associates, Hoag Memorial Hospital Cancer Center, Newport Beach, CA states that brain metastases resulting from primary ovarian cancer are rare, however, there have been recent studies suggesting an increased incidence of brain metastases (PubMed PMID: 14984970).

Greg

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