Taxol, the good the bad and the rest.

california_artist

The Good. If you read the entire article, you will understand that this information is information that will help you not only tolerate Taxol better, but have it be BOTH LESS TOXIC AND MORE EFFECTIVE. I have posted this article before and for some reason, most miss that this article conveys good news for those taking Taxol. I am trying to help you have a more favorable outcome.

We all need to get well by using whatever means works, that's works, for us as individuals.

Because Taxol is the main chemo agent used for uterine cancer, it is good to know all one can about it.

Taxol appears to be highly effective in those cancers that are ER/PR +, but not nearly as effective for those cancers like uterine papillary serous carcinoma, which is ER/PR-.

The following article talks of how to make Taxol more effective-AND LESSEN ITS TOXICITY-- for those taking it over time usually after recurring by using turmeric (curcumin).

The study was funded by the United States Department of Defense. Co-authors include Shishir Shishodia, Ph.D.; Yasunari Takada, Ph.D.; Sanjeev Banerjee, Ph.D.; Robert A. Newman, Ph.D.; Carlos Bueso-Ramos, M.D., Ph.D.; and Janet E. Price, Ph.D. I AM ADDING TO THIS BECAUSE I'M NOT SURE THAT THE GIST OF THE INFO WAS CLEAR SO:They are talking about taxol and breast cancer, but they are talking about taxol, which I do believe can initially be very effective in treating non pap serous endo cancers.Then they go on to discuss -TaXOL USED OVER TIME: They say: Because Taxol is so toxic, it activates a protein that produces an inflammatory response that induces metastasis.But and here's the good news-talking about curcumin(an ingredient in easily obtainable turmeric): researchers found that the nontoxic natural substance not only repelled progression of the disease to the lungs, but also appeared to reverse the effects of paclitaxel (Taxol TM ), a commonly prescribed chemotherapy for breast cancer that may trigger spread of the disease with use over a long period of time. It mentions that curcumin lessens the toxicity of taxol by specifically breaking the dose into more manageable size, thus giving cancer less of a target to respond to negatively.Article further states: In fact, researchers found that adding curcumin to Taxol actually enhances its effects.and this:Curcumin breaks down the dose, making the therapy less toxic and just as powerful while delivering the same level of efficacy.I had read this before in regard to the combo.Honestly, what's not to love about this news.So, all in all, I read this as very good news potentially. I am sure that other universities will be picking up on this and adding their research findings either in support or not. But basically it could potentially help those with recurrences have a far better response to Taxol.Anyone wishing further information or critique would be well advised to contact the original researchers or M.D.Anderson directly for current status, it is not my study, I'm just putting it out there. TRULY HOPE SOME OF YOU BRING THE INFO TO THE ATTENTION OF YOUR DOCTORS. BEST WISHES TO YOU ALLTHE ABOVE EDITS WERE ADDED ON SEPT 30, 2011-since it appears that some are highly sensitive to edits.Early Study Shows Spice Stunts Deadly Spread To LungsScienceDaily (Oct. 16, 2005) — HOUSTON - Curcumin, the main ingredient of turmeric and the compound that gives curry its mustard-yellow color, inhibits metastasis to the lungs of mice with breast cancer, report researchers at The University of Texas M. D. Anderson Cancer Center. [My comments: I do think this is worth reading. Talks of turmerics beneficial use in conjunction with Taxol. the spaces in the article were put there by me so it would be easier to see why you might be interested, everything else in the same. I thought I had posted this but didn't see it anywhere. Might be something to bring to the attention of your doctors.]--------------------------------------------------------------------------------The study, to be published in the Oct. 15 issue of the journal Clinical Cancer Research, reports that the spice appears to shut down a protein active in the spread of breast cancer to a major target for metastasis.Though the study results are early, researchers found that the nontoxic natural substance not only repelled progression of the disease to the lungs, but also appeared to reverse the effects of paclitaxel (Taxol TM ), a commonly prescribed chemotherapy for breast cancer that may trigger spread of the disease with use over a long period of time. Because Taxol is so toxic, it activates a protein that produces an inflammatory response that induces metastasis. Curcumin suppresses this response, making it impossible for the cancer to spread.In fact, researchers found that adding curcumin to Taxol actually enhances its effect.Curcumin breaks down the dose, making the therapy less toxic and just as powerful while delivering the same level of efficacy."We are excited about the results of the study and the possible implications for taking the findings into the clinic in the next several years," says Bharat Aggarwal, Ph.D., professor of cancer medicine in M. D. Anderson's Department of Experimental Therapeutics. "At this time, advanced breast cancer is a difficult foe to fight with few proven treatments available after surgery, chemotherapy and radiation therapy."Taxol is currently used as the front-line chemotherapeutic agent in breast cancers, but because the drug frequently induces drug resistance after prolonged use, it is not effective in treating metastatic breast cancer, says Aggarwal.Researchers studied 60 mice with breast cancer, which were randomly assigned to one of four groups: control group, Taxol only, curcumin only and the combination of Taxol and curcumin. After the tumors grew to 10 mm (about the size of a pea), they were surgically removed, and the mice were fed a powdered curcumin diet.Macroscopic lung metastasis, or metastasis that is visible to the naked eye, was seen in 96 percent of the mice in the control group. Treatment using Taxol alone only "modestly reduced" the incidence of metastases, while the group using curcumin alone and curcumin plus Taxol "significantly reduced" both the incidence and numbers of visible lung metastases. Microscopic metastasis, or metastasis that is visible only when using a microscope, was found in the lungs of 28 percent of mice treated with the combination of curcumin and Taxol, and there was no macroscopic disease present. The micrometastases present consisted of only a few cells, suggesting that the combination inhibited the growth of breast cancer tumor cells that were in the lung before the tumors were removed. In a previous study published in the Aug. 15 issue of the journal Cancer, M. D. Anderson researchers found that when the nuclear factor-kappa B (NF-kB) (a powerful protein known to promote the inflammatory response necessary to cause breast cancer to spread) is shut down, cancer strains are unable to grow and cells are pushed to commit suicide. The mechanism in this curcumin study works the same way. Taxol activated the NF-kB in breast cancer cells, while curcumin stopped this activation by blocking the protein known as "IKK" that switched on the NF-kB, demonstrating how curcumin and Taxol work against one another. Taxol produced the inflammatory response, triggering metastasis, and curcumin suppressed it, causing cell death. Extracted from the roots of the curcuma longa plant, curcumin is a member of the ginger family. While it is not used in conventional medicine, it is widely prescribed in Indian medicine as a potent remedy for liver disorders, rheumatism, diabetic wounds, runny nose, cough and sinusitis. Traditional Chinese medicine uses curcumin as a treatment for diseases associated with abdominal pain, and it is used in ancient Hindu medicine as a treatment for sprains and swelling. According to the American Cancer Society, the chance of a woman having invasive breast cancer sometime during her life is one in eight. About 211,240 women in the United States will be diagnosed with invasive breast cancer in 2005, and approximately 40,410 women will die from the disease this year.###The study was funded by the United States Department of Defense. Co-authors include Shishir Shishodia, Ph.D.; Yasunari Takada, Ph.D.; Sanjeev Banerjee, Ph.D.; Robert A. Newman, Ph.D.; Carlos Bueso-Ramos, M.D., Ph.D.; and Janet E.

Price, Ph.D.

So, there's that.

california_artist

The Bad-I think we should have access to the most information
October 19, 2011 - 12:08am
Just thought it might be helpful for people to also be aware of
some risks associated with Taxol. My onc did not mention most of these.
This is from 1996 but since Taxol is more that forty years old, felt it relevant still. Also please take note of the author of this report as it not me. Any corrections or criticisms can be directed to the university:

"...Taxol has a variety of harmful side effects particularly producing alterations in liver function. During taxol clearance, the liver may accumulate a 25-fold higher concentration than that found in the plasma, which may induce alterations in liver function. When isolated rat hepatocytes were exposed to taxol, aerobic metabolism was reduced, leading to an insufficient increase of the ATP via anaerobic glycolysis. The respiratory chain is also directly affected by this drug (Manzano et al., l996) Several other toxic side effects have been attributed to taxol, including hypersensitivity reactions, cardiotoxicity, neutropenia, peripheral neuropathy, mucositis, gastrointestinal toxicities, alopecia, arthralgias, and myalgias (Gotaskie and Andreassi, 1994). Myelosuppression, especially neutropenia, appears to be the dose-limiting toxicity in solid tumors at 200-250 mg/m2. Sensory neurotoxicity with typical numbness, tingling and painful paraesthesial in the extremities, diarrhea, and alopecia appear frequently. Mucositis appears to be the non-haemotological dose-limiting side effect at 390 mg/m2 that has been determined in patients with leukemia. Mypersensitivity reactions which have been fatal might be schedule dependent. Anti-allergic prophylaxis must be given, although this precaution may not be considered to fully protective (Guchelaar et al., 1994). Taxol also can suppress the immune systems of patients, deaden sensory nerves or cause nausea and hair loss (Nicoloau et al., 1996)...."

http://klemow.wilkes.edu/Taxus.html

This paper was developed as part of the BIO 368 - Medical Botany course offered at Wilkes University during the summer of 1997. Course instructor was Kenneth M. Klemow, Ph.D. (kklemow@wilkes.edu). The information contained herein is based on published sources, and is made available for academic purposes only. No warrantees, expressed or implied, are made about the medical usefulness or dangers associated with the plant species in question.
Return to Plant Summaries page

This page posted and maintained by Kenneth M. Klemow, Ph.D., Biology Department, Wilkes University, Wilkes-Barre, PA 18766. (570) 408-4758, kklemow@wilkes.edu.

california_artist

california_artist said:

The Bad-I think we should have access to the most information
October 19, 2011 - 12:08am
Just thought it might be helpful for people to also be aware of
some risks associated with Taxol. My onc did not mention most of these.
This is from 1996 but since Taxol is more that forty years old, felt it relevant still. Also please take note of the author of this report as it not me. Any corrections or criticisms can be directed to the university:

"...Taxol has a variety of harmful side effects particularly producing alterations in liver function. During taxol clearance, the liver may accumulate a 25-fold higher concentration than that found in the plasma, which may induce alterations in liver function. When isolated rat hepatocytes were exposed to taxol, aerobic metabolism was reduced, leading to an insufficient increase of the ATP via anaerobic glycolysis. The respiratory chain is also directly affected by this drug (Manzano et al., l996) Several other toxic side effects have been attributed to taxol, including hypersensitivity reactions, cardiotoxicity, neutropenia, peripheral neuropathy, mucositis, gastrointestinal toxicities, alopecia, arthralgias, and myalgias (Gotaskie and Andreassi, 1994). Myelosuppression, especially neutropenia, appears to be the dose-limiting toxicity in solid tumors at 200-250 mg/m2. Sensory neurotoxicity with typical numbness, tingling and painful paraesthesial in the extremities, diarrhea, and alopecia appear frequently. Mucositis appears to be the non-haemotological dose-limiting side effect at 390 mg/m2 that has been determined in patients with leukemia. Mypersensitivity reactions which have been fatal might be schedule dependent. Anti-allergic prophylaxis must be given, although this precaution may not be considered to fully protective (Guchelaar et al., 1994). Taxol also can suppress the immune systems of patients, deaden sensory nerves or cause nausea and hair loss (Nicoloau et al., 1996)...."

http://klemow.wilkes.edu/Taxus.html

This paper was developed as part of the BIO 368 - Medical Botany course offered at Wilkes University during the summer of 1997. Course instructor was Kenneth M. Klemow, Ph.D. (kklemow@wilkes.edu). The information contained herein is based on published sources, and is made available for academic purposes only. No warrantees, expressed or implied, are made about the medical usefulness or dangers associated with the plant species in question.
Return to Plant Summaries page

This page posted and maintained by Kenneth M. Klemow, Ph.D., Biology Department, Wilkes University, Wilkes-Barre, PA 18766. (570) 408-4758, kklemow@wilkes.edu.

The not so good. I hadn't heard of this, it was posted within
The following report is from the NIH.

Me:the last few days on the Ovarian side by gdpawel, who's opinion I think highly of.
Here's the reasoning for posting this here. For the most part when we are given CT's or PET's, we do not have out heads scanned, with this information, which you can choose to take to your doctor, you might be able to have scans of your head also if you have had your cancer for a while. The more infor you have the more you can choose to ask about how things will effect your life. --

October 22, 2011 - 12:24pm
The report:
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.

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

barbakamom

california_artist said:

The Bad-I think we should have access to the most information
October 19, 2011 - 12:08am
Just thought it might be helpful for people to also be aware of
some risks associated with Taxol. My onc did not mention most of these.
This is from 1996 but since Taxol is more that forty years old, felt it relevant still. Also please take note of the author of this report as it not me. Any corrections or criticisms can be directed to the university:

"...Taxol has a variety of harmful side effects particularly producing alterations in liver function. During taxol clearance, the liver may accumulate a 25-fold higher concentration than that found in the plasma, which may induce alterations in liver function. When isolated rat hepatocytes were exposed to taxol, aerobic metabolism was reduced, leading to an insufficient increase of the ATP via anaerobic glycolysis. The respiratory chain is also directly affected by this drug (Manzano et al., l996) Several other toxic side effects have been attributed to taxol, including hypersensitivity reactions, cardiotoxicity, neutropenia, peripheral neuropathy, mucositis, gastrointestinal toxicities, alopecia, arthralgias, and myalgias (Gotaskie and Andreassi, 1994). Myelosuppression, especially neutropenia, appears to be the dose-limiting toxicity in solid tumors at 200-250 mg/m2. Sensory neurotoxicity with typical numbness, tingling and painful paraesthesial in the extremities, diarrhea, and alopecia appear frequently. Mucositis appears to be the non-haemotological dose-limiting side effect at 390 mg/m2 that has been determined in patients with leukemia. Mypersensitivity reactions which have been fatal might be schedule dependent. Anti-allergic prophylaxis must be given, although this precaution may not be considered to fully protective (Guchelaar et al., 1994). Taxol also can suppress the immune systems of patients, deaden sensory nerves or cause nausea and hair loss (Nicoloau et al., 1996)...."

http://klemow.wilkes.edu/Taxus.html

This paper was developed as part of the BIO 368 - Medical Botany course offered at Wilkes University during the summer of 1997. Course instructor was Kenneth M. Klemow, Ph.D. (kklemow@wilkes.edu). The information contained herein is based on published sources, and is made available for academic purposes only. No warrantees, expressed or implied, are made about the medical usefulness or dangers associated with the plant species in question.
Return to Plant Summaries page

This page posted and maintained by Kenneth M. Klemow, Ph.D., Biology Department, Wilkes University, Wilkes-Barre, PA 18766. (570) 408-4758, kklemow@wilkes.edu.

Hypersensitive to Taxol
During my first round of chemo for uterine adenocarcinoma with mets to lungs, I took the taxol/carboplatin combo of chemotherapy and stopped breathing - ending up in ICU with severe reaction to Taxol. Finished with 2 rounds of carboplatin only. CA125 went from 90 to 6-7 post surgery, with clear CT scans for 11 months now. I'm wondering how using just carboplatin and not Taxol, and only being able to tolerate 3 of the planned 6 rounds of chemo will affect me. Now that I'm participating in these posts, I have a better understanding that I'm in this for the long haul, so thank you all for sharing your stories.
~Barbara