Author:
Gregory D. Pawelski
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Date Posted: 02:45:52 03/16/04 Tue
Chemo resistance may be the one reason many ovarian cancer patients are only receiving very short remissions (not cures). The effectiveness of taxol/carboplatin combination is limited because of the late stages of recurrent ovarian cancer and most patients develop resistance. Most cancer patients have the drug bounce off their tumors, doing little if any good. Because of the "dose-intense" nature of the treatment, it also suppresses the immune system, making it possible new tumors to grow because the patient has been rendered unable to resist them.
The body's immune system attacks and eliminates not only bacteria and other foreign substances but also cancer cells. Cancer cells are not foreign to the body but their biological function has been altered in that it doesn't respond to the body's normal mechanisms for controlling cell growth and reproduction. The abnormal cells can continue to grow, resulting in cancer. Much of the body's protection against cancer is carried out directly by cells of the immune system rather than by antibodies circulating in the bloodstream. A malfunctioning immune system can fail to stop the growth of cancer cells.
It has not been shown that platinum-based combination therapy is superior to single agent alkylator therapy. No substantial benefit has been found in giving ovarian cancer patients this therapy. Clinicians have found that the toxic effects of this treatment can cause a lower quality of life for these patients.
Taxol does not improve standard first-line ovarian cancer treatment. Studies (Lancet - August 17, 2002 edition) suggest that for initial treatment of women with ovarian cancer, widely used standard drugs are equally as effective as treatments that include Taxol and Carboplatin and may be considered the preferred treatment as they have fewer side effects. The results of these studies doesn't mean that Taxol has not role in the treatment of ovarian cancer, but they allow doctors and ovarian cancer patients to have choices according to each individual's needs.
Also of note, some combination chemotherapy drugs do permeate (pass through) the blood brain barrier (the system that protects the brain from foreign substances by blocking their passage from the blood). A group of platinum based drugs like Cisplatin and Carboplatin are such drugs and natural substances such as Taxol, also cross the barrier (there are others).
In recent years, the incidence of central nervous system (CNS) metastasis has increased. Unfortunately, some these chemotherapeutic agents weaken the blood-brain barrier (BBB) transiently and allow CNS seeding. Taxol with Carboplatin are two of the drugs that violate the blood-brain barrier (dose dependent). In essence, it breaks down, damages the blood-brain barrier to invite microscopic cancer cells into the Central Nervous System. A NCI observational study in 1995 reported experience in their clinic where recurrent systemic disease occurred in all patients for which they received dose intense Paclitaxel (Taxol) therapy. Brain metastasis was the only site of disease recurrence. I've had numerous cancer patients and loved ones of cancer patients who have written to me (because of my extensive postings and articles on the internet) with their experience with brain mets after dose intense taxol/carboplatin regimens. These patients had either ovarian, breast or lung cancers.
The jury is out on how ovarian cancer spreads. As less is known about this disease than other cancers, this has not been definatively answered and there is controversy amoung 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 may 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 drugs (Carboplatin) maybe weakening the blood brain barrier (but that does not explain "every" instance).
If you understand the politics of the Chemotherapy Drug Concession, oncologists have the financial incentive to select certain forms of chemotherapy over others because they receive higher reimbursement. Typically, doctors give patients prescriptions for drugs that are then filled at pharmacies. But medical oncologists buy the chemotherapy drugs themselves, often at prices discounted by drug manufacturers trying to sell more of their products and then administer them intravenously to patients in their offices. the practice creates a potential conflict of interest for these doctors, who must help cancer patients decide whether to undergo chemotherapy or not or to continue if it is not proving to be effective and which drugs to use.
Chemosensitivity Testing
Fresh samples of the patient's tumor from surgery or a biopsy are grown in test tubes and tested with various drugs. Drugs that are most effective in killing the cultured cells are recommended for treatment. Chemosensitivity testing does have predictive value, especially in predicting what "won't" work. Patients who have been through several chemotherapy regimens and are running out of options might want to consider chemosensitivity testing. It might help you find the best option or save you from fruitless additional treatment.
This kind of testing can assist in individualizing cancer therapy by providing information about the likely response of an individual patient's tumor to proposed therapy. In instances of severe drug hypersensitivity, failed therapy, recurrent disease and metastatic disease, it can provide assistance in selecting optimal chemotherapy regimens. Today, chemosensitivity testing has progressed to the point where it is 85% - 90% effective.
All available chemosensitivity assays are able to report drug "resistance" information. Resistance implies that when a patient's cancer cells are exposed to a particular chemotherapy agent in the laboratory, the cancer cells will continue to live and grow. Some chemosensitivity assays are also able to report drug "sensitivity" information. Sensitivity implies that when a patient's cancer cells are treated with a particular chemotherapy agent in the laboratory, that agent will kill the cancer cells or inhibit their proliferation.
Listing of "Reputable" Labs USA:
These labs will provide you and your physician with in depth information and research on the testing they provide.
Analytical Biosystems, Inc., Providence, Rhode Island. Ken Blackman, PhD. Solid Tumors Only. 1-800-262-6520
Anticancer, Inc., San Diego, CA. Robert Hoffman, PhD. Solid Tumors Only. 1-619-654-2555
Oncotech, Inc., Irvine, CA. John Fruehauf, MD. Solid Tumors and Hematologics. 1-714-474-9262 / FAX 1-714-474-8147
Sylvester Cancer Institute, Miami, FL. Bernd-Uwe Sevin, MD. Solid Tumors Only. (especially GYN). 1-305-547-6875
Human Tumor Cloning Laboratory, San Antonio, TX. Daniel D. Von Hoff, MD. Solid Tumors Only. 1-210-677-3827
Rational Therapeutics Institute, Long Beach, CA. Robert A. Nagourney, MD Solid Tumors and Hematologics. 562-989-6455 http://www.rational-t.com/
Weisenthal Cancer Group, Huntington Beach, CA. Larry M. Weisenthal, MD, PhD. Solid Tumors and Hematologics. 1-714-894-0011 / FAX 1-714-893-3659 / e-mail: mail@weisenthal.org
One interesting note about Dr. Larry Weisenthal (Weisenthal Cancer Group). Someone very close to him had advanced ovarian cancer a few years ago. She underwent heroic debulking surgery (from pelvic floor to diaphragm) and tissue specimens were sent for chemosensitivity testing which showed resistance to single agent cisplatin and carboplatin and resistance to taxol. The three drug combination of vinorelbine, gemcitabin and high dose tamoxifen was very synergistic and tested sensitive. She was treated with 6 cycles of gemcitabine, carboplatin, vinorelbine and high dose tamoxifen with only minimal nausea and with no other toxicity. Her CA-125 normalized, her bowel symptomatology normalized and she gained back all of the 25 or so pounds which she had lost. She stated that she now feels better than she has in years and will undergo a second laparotomy sometime soon. This person "never" would have benefited with taxol/carboplatin.
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