Der Extrakt aus dem Prostatakrebs-Forum von KISP und BPS

Therapiearten – Chemotherapie

["Bei der Chemotherapie werden aggressive Zellgifte (Zytostatika) eingesetzt, die auf unterschiedliche Weise in die Vermehrung von Zellgiften eingreifen. Weil Tumorzellen sich häufiger teilen als die meisten anderen Körperzellen, sind Geschwulste und Metastasen für Zytostatika besonders anfällig: Sie können schrumpfen, und mitunter verschwinden sie sogar ganz. Allerdings können auch gesunde Zellen, die sich rasch teilen, geschädigt werden: die Zellen der Haarwurzeln etwa, aber auch die Blut bildenden Zellen des Knochenmarks." (Aus dem SPIEGEL, Heft 41/2004, ein Bericht, der sich kritisch mit Chemotherapien auseinandersetzt und ihre tatsächliche Wirksamkeit bezweifelt).
Über Chemotherapien gegen Knochenmetastasen liegen noch bedauerlich wenige Beiträge vor. In einigen Erfahrungsberichten wird auch die jeweils angewandte Medikamentierung geschildert. - Ed]
Ralf schrieb am 28.2.2004:
wie manche von Euch vielleicht noch wissen, nahm Uwe kurz vor seinem Tod einen neuen Text in seine Themenliste auf, "Chemo-Therapie", geschrieben von Frau Prof. Elke Jäger vom Krankenhaus Nordwest in Frankfurt/M. Er bereitete noch eine weitere Seite über Nebenwirkungen solcher Chemotherapien vor (Uwe bevorzugte den Ausdruck "Negativwirkungen"), den ihm PD Dr. Eckhart Weidmann, Oberarzt bei Frau Prof. Jäger, schreiben wollte. Ich fand diese vorbereitete Seite in Uwes Nachlass.
Auf meine Bitte hin (weitergeleitet durch Gerd U.) hat Herr Dr. Weidmann diesen Beitrag jetzt geschrieben. Ich habe ihn in die vorbereitete Seite eingearbeitet und heute auf den Server hochgeladen. Er ist zu finden im fünften Block von Uwes Themenliste.
Rita schrieb am 7.3.2004 direkt an den Editor:
Mein Mann bekommt einmal pro Woche je eine Infusion Selenase, Kevatril, Sostril, Fortecortin, Taxotere 60 mg, NaCl-Lösung zum Nachspülen. Dauert zusammen etwa vier Stunden. Nach sechs Behandlungen eine Woche Pause. Dann wieder sechs Behandlungen. Mein Mann hat jetzt insgesamt sieben Therapien hinter sich. Einen Tag vor der Behandlung 60 Tabletten Calcitrol.
Super Verbesserung bisher, kaum Nebenwirkungen.
HWL schrieb am 7.8.2004:
Für die Betroffenen, bei denen die Nebenwirkungen einer Chemo- oder Strahlentherapie durch die Gabe von Glukokortikoiden gemildert werden, dürfte nachstehende Pressemitteilung des DKFZ(Deutsches Krebsforschungszentrum) vom 16.Juni 2003 von Interesse sein. Die Meldung galt im Jahr 2003 für bestimmte Krebsarten. Da in dem Bericht die Auswirkungen von Steroidhormonen auf den PCa nicht speziell erwähnt werden, sollten sich näher Interessierte direkt im DKFZ nach dem aktuellen Stand der Forschungen erkundigen.
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Probleme mit Glukokortikoiden in der Krebsbehandlung
Steroidhormone können den Erfolg einer Chemo- oder Strahlentherapie verhindern. Haarausfall, Übelkeit und Erbrechen – diese unerwünschten Nebenwirkungen einer Chemo- oder Strahlentherapie lassen sich häufig durch Glukokortikoide abmildern. Die begleitende Verabreichung dieser Steroidhormone gilt bisher als unverzichtbar in der Krebsbehandlung. Doch dieses Therapiekonzept muss möglicherweise bei bestimmten Krebsarten überdacht werden. Dies legen die Forschungsergebnisse nahe, die Privatdozentin Dr. Ingrid Herr, Deutsches Krebsforschungszentrum, sowie Prof. Klaus-Michael Debatin* und Prof. Magnus von Knebel Doeberitz* in der Fachzeitschrift Cancer Research** veröffentlicht hatten. Die Wissenschaftler stellten zusammen mit weiteren Kollegen aus Heidelberg fest, dass Glukokortikoide Zellen von Gebärmutterhals- und Lungentumoren gegen die Behandlung resistent machen.
Glukokortikoide wirken sich positiv auf das Allgemeinbefinden der Patienten während einer Therapie aus. Zudem lösen diese Steroidhormone bei Leukämiezellen den programmierten Zelltod, die Apoptose, aus und unterstützen somit den Therapieerfolg. Dies ist jedoch nicht der Fall bei soliden Tumoren, im Gegenteil: Gebärmutterhals- und Lungenkarzinome wachsen unter Glukokortikoidhormonen sogar schneller. An Zellen und an Mäusen untersuchte Ingrid Herr, wie die Substanz Dexamethason auf molekularer Ebene in die Signalkaskade des programmierten Zelltods eingreift. Sie fand heraus, dass das Glukokortikoid direkt und indirekt die Aktivität vieler Signalmoleküle beeinflusst und letztlich auch zwei entscheidende Komponenten, die Caspase-8 und -9, hemmt. Die Blockade dieser Enzyme ist offensichtlich der Hauptgrund dafür, dass die Zellen solider Tumoren nicht mehr auf die Therapie ansprechen. Diese Annahme hat Ingrid Herr mit einer weiteren Untersuchung untermauert: Bringt man die Gene der Caspasen oder ihre funktionsfähigen Produkte in die Tumorzellen ein, so werden diese wieder empfänglich für das Apoptosesignal und sterben ab.
Bislang sind die molekularen Abläufe nicht im einzelnen geklärt, und klinische Untersuchungen müssen sich anschließen, dennoch könnten die Ergebnisse weitreichende Auswirkungen auf den Einsatz von Glukokortikoiden in der Krebsbehandlung haben. Ingrid Herr und Kollegen überprüfen jetzt die Wirkung von Glukokortikoiden bei jeder einzelnen Krebsart, um eine differenzierte Aussage machen zu können.
*Prof. Klaus-Michael Debatin, der frühere Leiter der Klinischen Kooperationseinheit Molekulare Onkologie/Pädiatrie, ist derzeit Ärztlicher Direktor der Universitäts-Kinderklinik in Ulm.
*Prof. Magnus von Knebel Doeberitz ist heute Ärztlicher Direktor des Instituts für Molekulare Pathologie der Universität Heidelberg.
**"Glucocorticoid co-treatment induces apoptosis resistance towards cancer therapy in carcinomas", Ingrid Herr, Esat Ucur, Kerstin Herzer, Stella Okouoyo, Rüdiger Ridder, Peter Krammer, Magnus von Knebel Doeberitz and Klaus-Michael Debatin, Cancer Research, 63 (12), June 15, 2003.
DKFZ-Pressemitteilungen Nr. 31, 16. Juni 2003
Siegbert fragte am 24.8.2004:
Mein PSA-Wert stieg von 4,45 am 8.07. auf 6,10 am 10.08.04 (TRENANTONE am 2.08.04). MRT und CT im Juli haben eine PK-Metastase vor dem 2. Sakralwirbel [os sacrum = Kreuzbein - Ed] nachgewiesen, der gem. Urologie-Klinikum wieder bestrahlt werden sollte (letzte Bestrahlung am 1.6.04 im ehemaligen OP-Bereich). Knochenscan, CT-Thorax, Enddarm o.k.
Mit der vorgeschlagenen Therapie konnte ich mich nicht anfreunden und habe eine im Rhein-Main-Raum bekannte Onkologin hinzugezogen. Seit gestern Chemo mit 5-FU (sechs Wochen je 1 x) (Nebenwirkung bisher nur ztw. sehr leichte Übelkeit/flauer Magen) plus Zometa ab nächster Chemo. Was hilft gegen den flauen Magen?
Danach ist zunächst eine Ergänzung der weiter laufenden TRENANTONE-Behandlung mit Casodex o. ä. angedacht und erst später - sofern erforderlich - Taxotere und Estramustin. Casodex 50 (1 x tgl. zusätzlich zu TRENANTONE) wurden bei mir im Februar 04 nach 4,5 Monaten wegen weiter steigender PSA-Werte abgesetzt. Könnte Casodex in höherer Dosierung nach der Chemo doch noch helfen? Gibt es eine Alternative zu Casodex (Androgenrezeptorenmutation?)? Kennt ihr vergleichbare Fälle mit einer 2HB nach Chemo oder ist das nur Prinzip Hoffnung? Auch der Glaube an den Erfolg einer Therapie kann ja (nach Dr. CARL SIMONTON) ergänzend hilfreich sein.
Guy meinte am 25.8.2004:
Chemo mit 5-Fu als Monotherapie könnte eine Untertherapie sein. Lies bitte mal dazu http://www.prostatakrebs-bps.de/life_chemo.html.
Beim Darmkrebs ist 5-Fu schon durch Capecitabin ersetzt worden http://www.aerztezeitung.de/docs/2004/08/05/146a1504.asp?cat=/medizin/krebs
Zu Nebenwirkungen: http://www.prostatakrebse.de/themen/0058.htm
http://www.aerztezeitung.de/docs/2004/06/28/118a1101.asp?cat=/medizin/krebs/prostatakrebs
http://www.prostatakrebse.de/informationen/html/the_chemo.html
Und Urologe fs schrieb am selben Tag:
ich möchte es kurz machen: außer Taxotere/Cisplatin hat KEINE (!) chemotherapeutische Substanz auch nur einen Tag Überlebensvorteil zeigen können – nur schlechtere Lebensqualität.
Gegen den flauen Magen hatte Ralf, ebenfalls am 25.8.2004, den folgenden Vorschlag:
versuche doch mal kandierten Ingwer, drei oder vier "Brocken". Es gibt ihn in Gewürz- und Teegeschäften. Ich habe damit meinen während der DHB gegen Flutamid meuternden Magen etwas beruhigen können. Wunder kannst Du natürlich nicht erwarten, aber vielleicht hilft es ein bisschen.
Ein "Joe Doe" (etwa "Otto Normalverbraucher") schrieb am 13.7.2004 ohne weiteren Kommentar:
A Presentation by Charles E. Myers Jr., M.D. to the Kettering Medical Center Prostate Cancer Support Group on April 25, 2002
About E. Myers Jr., M.D.
http://www.prostateforum.com/about.htm
Advanced disease
"Now I’d like to skip over and talk about what I see as advances at the other end of the spectrum – those patients who have widespread disease when they are diagnosed or developed later. Widespread bony disease. Here again there is an ongoing revolution occurring in what we can do for men with advanced prostate cancer.
I first started working on this disease in 1987. For the first five years that I worked on prostate cancer, the conventional wisdom was that, if you became hormone refractory, you could expect to live six to eight months.
Now, I have to tell you I can’t remember the last time I saw a patient who was hormone refractory who died less than a year after becoming hormone refractory. Mainly you’re talking a couple of years, and maybe longer than that. And I think we can do far better than even that.
I was at a meeting in West Palm Beach, and one of the young investigators from M.D. Anderson got up and presented the results of their latest sets of clinical trials. They didn’t focus on the specific drugs, but pointed out that the median survival was 36 months across all their trials for hormone refractory disease. And, they only see men with very widespread disease and the worst kind of prostate cancer in those trials. There are many men with hormone refractory disease and cancers that grow much less rapidly than this, who are going to beat those figures.
I have a patient that became hormone refractory in 1994. He had one eight-week course of chemotherapy, and then using the drugs we just outlined to arrest the growth of the disease, his cancer remained in check until 2001. He had to have another course of chemotherapy. He’s back now on suppressive therapy, and for the past two years he’s been building a major winery just south of Santa Barbara.
What I want to combat particularly is that sense of overwhelming negativism that many men get when they’ve been diagnosed with hormone refractory disease, or that their physicians communicate to them because the physicians just don’t know what we can do in the hormone refractory setting.
But, of course, if you don’t have a positive mindset, and you don’t go out and get what can be done, you’ll have a bad outcome. You know a pessimist always has his worst fears confirmed, while unexpected good things tend to happen to optimists. So, what has happened with hormone refractory prostate cancer?
The first thing is that we now have a whole group of drug combinations that can cause more than half the patients to respond, and by responding I mean they have a more than 50% drop in their PSA. You might say, “How important is it for my PSA to drop by 50%?” Well, in every cancer center that has looked at this, when every drug combination has been used, a 50% drop in your PSA translates in a double year of your survival. That’s why people are not now dying in 7 to 8 months.
“When you say a 50% response rate, that means I only have a 50-50 chance of responding.” But, this was first pointed out to me by Ken Pienta at the University of Michigan, where he looked across his series of prostate cancer patients. He said, “While only 50% respond to this combination, we have three or four combinations, and you go from one to another, and 95% of patients are going to respond to one of these combinations.” So, almost every man who has hormone refractory prostate cancer can be made to have a response to chemotherapy. We just might not get it with the first one.
Then there’s something to understand...chemotherapy will cause an initial response. Over about the first 2-3 months the PSA will drop and tumor masses will shrink, and then it will plateau. You can keep giving chemotherapy, but it’s not going to get better than that. I think that’s when we stop that chemotherapy, when you’re just keeping a lid on it. The first person to show that this is a wise thing to do was Dan Petrylak from Columbia University. He was looking at Taxotere, which is one of the drugs we’re using. After the first 3-4 months when the response plateaued, he’d stop treatment. Then 3 or 4 months later he found he could go back in and re-treat, and using the exact same drugs the patient would respond again, and come down a plateau. Stop. Wait a couple of months, and repeat this. It’s though resistance was temporary, and disappear with 3 or 4 months off of chemotherapy.
Now, what a number of us are trying to do, and I’m not alone in this, is give the chemotherapy, drop the PSA by 50 to 90%, and then stop -- but don’t do nothing -- put the men on the drugs that slowed the growth of this cancer. In a number of patients I’m seeing, say starting with a PSA of 200, bring it down to 80 where it plateaus. Put them on drugs that keep the cancer from growing, and three months later the PSA may have gone from 80 to 100. Now you re-start chemotherapy and they go from 100 to 30. You end up going down a staircase like this, and of course the goal is to reach an undetectable PSA and complete remission. There are a number of medical oncologists who are taking this approach around the country. Already I can tell you that the quality of life is much, much better when you have a holiday off the chemotherapy. Those of you who have been on chemotherapy know how nice a holiday is.
Now there are some other things that have come out. Zometa is a drug that prevents the cancer from breaking bone down. It’s the most potent of the drugs in this series. Others include Actonel, Fosomax, Aredia. Zometa is the best of this group.
What the clinical trials show, if you have prostate cancer and you have a bony metastasis, and you’re put on Zometa, it dramatically reduces the risk that you will get new bony metastasis over the course of several years. So this is another very useful tool to prevent progression of the disease, without the side effects of chemotherapy.
Again, though, the mistake comes when the medical oncologist tries to approach this disease in piecemeal fashion and picks one of these. It’s like when you go swimming, and the water’s cold, and you stick your toe in, and inch in and how painful that is. When you’re using these approaches to the chemotherapy and hormone resistant prostate cancer, you need to do more like jumping in the cold lake right off the diving board. You need to put all the tools together that we have to approach the disease and do it in an integrated way where all phases are meant to work together.
One of the drugs we talked about at the very beginning now comes back to play a new role, Calcitriol. I think the single most exciting chemotherapy paper in the past two years was by Dr. Beer of the University of Oregon. What he showed is that if you get a single massive dose of Calcitriol 24 hours before chemotherapy, you don’t increase the side effects at all, but you dramatically increase the anti-tumor activity. He was specifically studying Taxotere, which is the most active single chemotherapy drug for prostate cancer. It took the response rate from about 40% to about 75%.
In the laboratory, the same approach dramatically improves the effectiveness of Carboplatin, another drug widely used in the treatment of prostate cancer. A number of medical oncologists are also using this. So you can see how all of these different tools that we have are suddenly more effective as we learn to use them better.
Dazu schrieb Guy am selben Tag:
Sehr gut recherchiert,
Jedoch siehe auch unter http://www.dorway.com/taxotere2.txt, wo gut erklärt wird von Dr. Myers, dass Taxotere + Estramustin bisher die wirksamste Chemo ist. Trotzdem besteht die Hoffnung das Hochdosis Calcitriol + Taxotere zumindest gleichwertig in der Wirkung ist mit weniger Nebenwirkungen.
In regards to chemotherapy Dr. Myers said that Taxotere is the most effective showing an effect in 40 - 45% of men. When combined with Calcitriol this percentage jumped to 70% with no increase in side effects.
About Dr. Charles Myers:
Charles E. Myers, M.D., is Founder and Director of The American Institute for Diseases of the Prostate (AIDP) and President of the Foundation for Cancer Research and Education. He is a professor of Internal Medicine at the University of Virginia where he was the Director of the Cancer Center from 1994 to 2001. Dr. Myers is an internationally recognized expert in prostate cancer research and treatment and is well known for his warm, personable style, and his ability to explain technical aspects of prostate cancer and its treatment. He is a frequent and popular speaker at support group meetings such as USTOO, PAACT and Man-to-Man. Dr. Myers is a co-author of “Eating Your Way to Better Health,” and is Editor of the Prostate Forum, a monthly newsletter for prostate cancer patients and their families
http://www.hormonerefractorypca.org
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http://www.pslgroup.com/dg/226622.htm
Vitamin D plus Taxotere
Title: Combining Vitamin D with Taxotere Provides Benefits for Advanced Prostate Cancer Treatment
URL: http://www.pslgroup.com/dg/226622.htm
Doctor's Guide, January 3, 2003
PORTLAND, OR -- January 2, 2003 -- The addition of high-dose calcitriol to weekly treatment with the chemotherapy agent docetaxel (Taxotere®) appears to improve the therapeutic response in men with androgen-independent prostate cancer without compromising safety, according to results published Jan. 1 in the Journal of Clinical Oncology. Calcitriol is the active form of vitamin D. Data from a phase II clinical trial suggest the combination of docetaxel/calcitriol is as much as twice as effective as the use of docetaxel alone, as measured by prostate-specific antigen (PSA) response rate. The results were so promising that a phase III trial has been launched at 15 sites throughout the United States.
"We're excited by these promising results, especially since there is no acceptable standard treatment for this type of prostate cancer," said Tomasz Beer, MD, an oncologist at the Oregon Health & Science University (OHSU) Cancer Institute in Portland, Oregon, and lead investigator of the study.
In the study, 31 of 37 patients, or 81 percent, who were treated with the combination regimen cut their PSA levels by more than half. In fact, 59 percent of patients achieved a confirmed PSA reduction of greater than 75 percent. Studies of docetaxel alone have reported a 42 percent PSA response rate. PSA is a substance produced within the prostate gland, and a high PSA level may indicate the presence of cancer. In patients with advanced prostate cancer, PSA correlates with the amount of cancer in the body.
In addition to PSA response, eight of 15 men in the study with measurable disease responded with significant reductions of their tumors.
"Based on this data we've opened a much larger study nationwide that should tell us whether these preliminary findings continue to hold true in larger patient populations," said Beer.
Patients in the study received oral calcitriol on the first day of the treatment cycle, followed by an infusion of docetaxel the next day. The treatment was repeated weekly for six weeks of an eight-week cycle until there was evidence of disease progression or unacceptable toxicity, or until the patient requested to be withdrawn from the study. Calcitriol is not the same as over-the-counter vitamin D, which could be harmful if taken in large doses.
About Prostate Cancer
Prostate cancer is the most common malignancy among men and the second leading cause of cancer death in men in the United States. The American Cancer Society estimated that in 2002 approximately 189,000 men were diagnosed with prostate cancer, and about 32,200 died as a result of the disease. Overall, roughly one in six American men will develop prostate cancer during his lifetime. If detected early, however, treatment can be highly effective.
About Oregon Health & Science University
Oregon Health & Science University is a health and research university focused on improving the well-being of people in Oregon and beyond. OHSU educates health practitioners, bioscientists, high-technology professionals, and environmental scientists and engineers, and it undertakes the indispensable functions of patient care, community service and biomedical research.
SOURCE: Oregon Health & Science University
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http://groups.google.com/groups?q=taxotere+and+prostate +cancer+group:sci.med.prostate.cancer&hl=en&lr=&ie=UTF-8&oe=UTF-8&group=sci.med.prostate.cancer&selm=R2fW4.15483%24S31.418418%40newsread2.prod.itd.earthlink.net&rnum=1
From: timothy roome (support@yahoocom)
Subject: "Dramatic"
View: Complete Thread (3 articles)
Original Format
Newsgroups: sci.med.prostate.cancer
Date: 2000/05/22
Taxotere/Estramustine Gives Longer Prostate Cancer Survival
Combined use of docetaxel (Taxotere) and estramustine phosphate (Emcyt) is highly active in men with an advanced form of prostate cancer-and use of the combination may dramatically improve survival, investigators reported at the 36th annual meeting of the American Society of Clinical Oncology (ASCO).
The study was conducted by a group from Columbia Presbyterian Medical Center in New York City and was the largest to evaluate the combination of docetaxel and estramustine in men with hormone-refractory prostate cancer. In all, 37 patients with hormone-refractory prostate cancer were treated with 280 mg of estramustine three times a day for 5 days, followed by 70 mg/m² of docetaxel given on the second day of the treatment course. The treatment was repeated every 3 weeks.
Of the enrolled patients, 25 men had a 50% or greater decrease in their prostate-specific antigen (PSA) levels, and 14 men had an 80% or greater decrease on two consecutive measurements at least 2 weeks apart. Five patients temporarily discontinued treatment when their prostate-specific antigen (PSA) level decreased to less than 4 ng/dL. Four of these patients were retreated when their PSA levels began to rise again. Three of the four patients achieved a 50% or greater decrease in their PSA levels after retreatment with the combination regimen. This finding indicated that some patients can discontinue treatment can be discontinued to allow them to for recovery from toxicity.
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http://groups.yahoo.com/group/taxotere/+prostate+cancer+taxotere
http://cdmrp.army.mil/
http://cdmrp.army.mil/pcrp/
http://cdmrp.army.mil/CWG/default.htm
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http://groups.google.com/groups?q=%2Bprostate%2Bcancer%2Btaxotere&ie=UTF-8&oe=UTF-8&hl=en&btnG=Google+Search
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An overall strategy for managing HRPCa
Conceptually, we believe that the most effective treatments for HRPCa are those that have already been proven. Our reasoning is that you need to get and keep this cancer under control to protect your life. There is time for experimentation after the cancer has been controlled.
We also follow new therapies with great hope, and we try some that seem to offer hope without risking our well-being. Our experience tells us to be conservative in selecting treatments, to choose those that have been established as effective for most men with HRPCa. Consequently, we spend our time searching for answers in the medical literature. Each man makes his own decisions in selecting treatments; and we respect that right. We have chosen the use of clinically proven therapies as our first line of battle.
The ideas we present here are rather straightforward. You may well be familiar with every treatment we suggest. What is important for you to realize is that there are a good number of available treatments that you can use to keep this disease at bay.
Three vital strategies
To hold back this disease, to extend your survival for years, to maintain your quality of life, you need to adopt these three strategies:
1. Keep your PSA as low as possible at all times. And verify the blood test values with bone scans and cat scans to avoid being blindsided by a tumor that doesn’t generate PSA. If at all possible, don’t let your PSA run uncontrolled for any reason! A rising PSA should never be ignored or accepted as “normal.” Although it is a truism that PCa is a slow-moving (i.e., slow-growing) cancer, you need to keep it suppressed to take advantage of that characteristic. When the PSA is low, say below 10, a number of supplemental treatments seem to be able to work, whereas they are ineffective against a larger tumor burden. When the PSA is high, say above 100, the risk of metastasis increases to an essential certainty. It is these metastases that cause pain and threaten life by damaging vital organs or leading to broken bones.
2. Prevent and suppress bone metastases with bisphosphonates. If you are on hormone therapy (testosterone blockade or orchiectomy), you must also start on a bisphosphonate. Don’t accept the argument that it is not necessary! The bisphosphonate set of drugs (Zometa, Aredia, Fosamax, Actonel) has been shown to maintain bone integrity in the face of hormone blockade. If you have had hormone therapy, you are almost certain to lose bone mass (osteopenia or osteoporosis) and suffer the risk of broken bones. Second, these drugs have been shown clinically to help suppress the cancer itself. By getting onto Zometa (a monthly IV) before you experience bone mets, you can realistically expect to postpone that unpleasant prospect indefinitely.
3. Maintain your overall health at the highest level possible. PCa brings with it the risk of heart disease, among other problems. You’ve not won the battle if you control the cancer but are killed by a heart attack, a blood clot, or an infection. The general practitioner is an important part of your medical team; explain to him that you are in a serious struggle with this cancer and that you will be relying on him to keep from being blindsided by some other unexpected health crisis. Blood clots are a concern with hormone therapy. Chemotherapy leads to a risk of infection, as well as many other health problems. You need to embrace a healthy life style. A low-fat diet, with several supplements, is best. You need to exercise to maintain your psychological health as well as your physiological systems. Do your routine preventive maintenance,including dental checkups to avoid oral infections.
The basic treatments for HRPCa
Most of us with HRPCa have gone through a similar battery of treatments. These are the treatments that have been shown to work in clinical trials. They have also worked for a significant number of men we know. Unfortunately, that also means that some of them don’t work sometimes.
The treatments listed here are also presented in greater detail in ensuing chapters. Issues of dosing, side effects, and monitoring are discussed. The purpose of this list is to let you know that there are many treatments available to control HRPCa.
The treatments are presented in the order in which they are usually tried (although there is no medical rule saying they must be done in this order). This order also runs generally from the treatments with the least severe side effects first.
1. Lupron or Zoladex. Chances are you’ve been on Lupron or Zoladex(or on one of the LHRH agonists provided outside the U.S.), perhaps for some years. Or you may have had an orchiectomy instead. In the case of Lupron or Zoladex, for example, you should plan to stay on this drug for the foreseeable future, preferably on a 28-84 day injection schedule. The Lupron or Zoladex will continue to suppress the testosterone that would otherwise stimulate the cancer cells to proliferate. HRPCa is a mixture of cancer cells, some of them still sensitive to hormone blockade. The Lupron or Zoladex you continue taking keeps those cells under control.
2. Bisphosphonate. See the discussion above.
3. An estrogenic drug, such as DES (diethyl stilbestrol). This drug has been used more frequently since the herbal remedy PC SPES was taken off the market. That remedy contained rather strong phytoestrogens. Although there is a general search underway for a replacement for PC SPES, we know of no equivalent at this time. With an estrogen, one must be aware of the risk of blood clots. Interestingly, these estrogenic drugs have been shown to work for some period of time with HRPCa, even in addition to the Lupron.
4. HDK + HC or LDK (high-dose ketoconazole plus hydrocortisone). Ketoconazole is an anti-androgen. It works by blocking the hormone receptors on the cancer cells, thus preventing access by cancer-stimulating testosterone. In the advanced stage, prostate cancer cells often acquire an overabundance of additional hormone receptors, with the result that even a minuscule amount of testosterone is sufficient to stimulate proliferation. The hydrocortisone is needed to replace the steroid lost when the ketoconazole shuts down that production by the adrenal glands. Some men have great success with taking HDK, and others have great difficulty with the side effects. Life most of these treatments, we only know if they are effective for a given individual when that person actually takes the drug.
5. Taxotere is the first of a number of chemotherapies that work with HRPCa. It is the most effective one against HRPCa. There are mixed feelings about using chemotherapy to fight cancer. The reactions include (1) a fear of the side effects and (2) a concern that the use of chemotherapy will disqualify them from consideration for clinical trials. The decision is up to the individual. However, it is unwise to let the PSA increase to the point at which there are widespread metastases. It is true that chemotherapy is not an easy treatment; the side effects include fatigue, some nausea, and peripheral neuropathy (numbness in feet and hands) to mention the most bothersome. However, it does bring down the PSA, and it does extend survival (despite some medical claims) when used in a series of treatments. Insofar as the concern about clinical trials goes, one should not let the PSA run out of control purely for the hope that something experimental might work. Most of the members of our support list have had chemotherapy treatments and can answer any questions about the experience.
6. At this point, there are a number of supplemental treatments that are being used to enhance the effectiveness of chemotherapy or to achieve some other advantage against HRPCa. These include megadoses of calcitriol to enhance the chemotherapy; Dostinex to suppress the prolactin level and reduce the PSA; Celebrex to inhibit one of the enzymes that promotes cancer growth; Periostat to suppress angiogenesis the aids cancer growth. Evista (raloxifene) and HDK are being evaluated as alternating treatments between bouts of chemotherapy. The selection of appropriate supplemental treatments depends on the individual and the disease status. The important thing about these supplements is that they have been shown to help in some cases, with no undue risk due to side effects. The regimen needs to be worked out with a knowledgeable physician—the expert on your medical team.
7 If the Taxotere fails to work, then Emcyt may be added. This chemotherapy, which includes an estrogen, enhances the effectiveness of the Taxotere (or other chemotherapy). The Emcyt causes some problems with nausea.
8. The next chemotherapy may be a combination of Navelbine and Emcyt. Or it may be another combination recommended by your expert. Different chemotherapy regimens work for different people for different periods of time.
9. Next in line is the combination of Taxol (in the taxane family with Taxotere), carboplatin, and Emcyt. Sometimes this combination is used without the Emcyt. There seems to be no way to ensure ahead of time whether a particular chemo regimen will work for a particular individual.
10. At this point, it is important to realize that some drugs fail due to protective mutation by the body’s cells. However, several months off the drug often results in the disappearance of the protective change; and the drug again becomes effective. The second time around may be shorter than the first; nonetheless, the reuse of a drug means that survival time is extended.
11. Another chemotherapy that often works is Novantrone plus prednisone (steroid). Adriamycin is also used sometimes, although there is a risk of cardiotoxicity.
This list of treatments will, hopefully, provide years of extended survival, years in which we will continue the search for better answers. Even during the few years that our support group has been in operation we have seen new ideas introduced that extend survival and improve the quality of life.
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Frequently Asked Questions
Below are some common questions about Taxotere® (docetaxel) for Injection Concentrate.
What is Taxotere and how does it work against cancer?
Like other anticancer medications, Taxotere works by attacking cancer cells in the body. Different medications attack cancer cells in
different ways.
Most chemotherapy drugs stop cancer cells from dividing by interfering with the cell's DNA, but Taxotere acts quite differently. Taxotere damages the supporting structure of the tumor cell, which is like a skeleton, thereby preventing the cell from growing and dividing.
How often is Taxotere treatment given?
Taxotere is given intravenously (through a vein) every 3 weeks. Each treatment takes about 1 hour. Again, every person is different. Only a doctor can determine what dose of Taxotere is right and how often to give it.
Is it necessary to take other medications with Taxotere treatment?
As part of a treatment plan, a doctor may prescribe other medications to lessen some of the side effects during treatment. A corticosteroid such as dexamethasone may prevent fluid retention (holding extra water in the body), and may also reduce any allergic reactions to Taxotere. If needed, a corticosteroid is usually taken 1 day before Taxotere treatment and continued for a total of 3 days. However, people receiving Taxotere should always follow their doctor's or nurse's instructions about how to take medications.
If a patient forgets to take their prescribed corticosteroid as directed, the doctor or nurse should be alerted before the next Taxotere treatment. A doctor or nurse should be notified of any problems with taking a medication.
Your doctor may also prescribe certain medicines to prevent nausea and vomiting. To learn more about an Aventis Pharmaceuticals product for the treatment of nausea and vomiting, click here.
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What are some of the side effects of corticosteroid pretreatment?
Use of a short course of a corticosteroids such as dexamethasone can cause side effects, although they are generally mild in nature. These side effects can include flushing, temporary mood changes, increased appetite, elevated blood sugar, and stomach irritation. Patients who have previously had side effects while taking corticosteroids should alert their physician or nurse before receiving treatment with Taxotere.
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Are there any medications that can't be taken during Taxotere treatment?
Some medications should not be taken because they might interact with Taxotere. Interactions can cause side effects and they may keep the medications from working. Patients should take only medications that the doctor prescribes and be sure that the doctor who is giving them Taxotere knows about all other medications they are taking, including nonprescription (over-the-counter) products and those prescribed by other doctors. Likewise, any other doctors who treat patients receiving Taxotere should know that they are receiving chemotherapy.
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Side Effects
Chemotherapy medications are powerful so they can work to destroy cancer cells. But because they are so powerful, side effects with chemotherapy are common. Like all anticancer agents, there are some side effects associated with Taxotere® (docetaxel) for Injection Concentrate that may be bothersome or difficult to tolerate. These may include low white blood cell count, hair loss, fatigue, fluid retention, numbness, mouth irritation, cutaneous changes, nausea and diarrhea.
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Interaction With Other Drugs
It is very important that people take only medications that their doctors prescribe for them. During treatment for cancer, people may take many different types of medications, both to treat cancer and to ease bothersome side effects. Since it can be confusing to remember all the names of the medications, it's important to keep a written record of all current prescription and non-prescription (over-the-counter) medications.
Certain medications can react with each other (even simple over-the-counter drugs) and cause unwanted side effects, or even become ineffective. It's important that the doctor who is administering Taxotere® (docetaxel) for Injection Concentrate knows about all other medications a person is taking. People should tell their doctor about non-prescription drugs, nutritional supplements, and herbs they use and medications prescribed by other doctors. Likewise, it's important that other doctors treating a person know that he/she is receiving chemotherapy.
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http://www.cancerbacup.org.uk/info/taxotere.htm
Possible side effects
Temporary reduction in bone marrow function. This can result in anaemia, risk of bruising or bleeding and infection. This effect can begin about 7 days after the treatment has been given and usually reaches its lowest point at 10-14 days after the chemotherapy. Your blood count will then increase steadily and will usually return to normal within 21 days.
The extent to which your blood count is reduced depends on the dose of chemotherapy you receive and which other chemotherapy drugs, if any, are given in combination. Your doctor can advise you how likely it is that your blood count will be lowered by the chemotherapy. Your blood count will be checked regularly to see how well your bone marrow is working.
If your temperature goes above 38C (100.5F), or you develop any unexplained bruising or bleeding, or you suddenly feel unwell, even with a normal temperature, contact your doctor or the hospital straight away.
Nausea and vomiting. This is usually mild. There are now very effective anti-sickness drugs to prevent or substantially reduce this. If it does happen it may begin a few hours after the treatment is given. If the sickness is not controlled, or continues, tell your doctor. They can prescribe other anti-sickness drugs which may be more effective.
Mouth sores and ulcers. If your mouth becomes sore, or you notice small ulcers, let your doctor know. They can prescribe suitable mouth care for you.
Diarrhoea. This can usually be easily controlled with medicine but let your doctor know if it is severe or persistent. It is important to drink plenty of fluids if you do get diarrhoea.
Hair loss. This usually starts 2-3 weeks after the first dose of docetaxel, although it may occur earlier. Hair may be lost completely or may just thin. You may also experience thinning and loss of eyelashes, eyebrows and other body hair. This is temporary: the hair will return to normal once the treatment is finished. CancerBACUP has a booklet called Coping with hair loss which we would be pleased to send you.
Skin changes. Docetaxel can cause a rash. Your doctor can prescribe medicine to help with this.
Soreness and redness of the palms of the hands and soles of the feet (sometimes known as Palmar Planter syndrome). This is temporary and will improve when treatment is finished.
Allergic reaction. Signs of an allergic reaction include skin rashes and itching, high temperature, shivering, redness of the face, a feeling of dizziness, headache, shortness of breath, anxiety and a need to pass urine. You will be monitored for any signs of an allergic reaction during the treatment. Tell your doctor or nurse if you have any of these symptoms. A course of steroids is often prescribed to reduce the chance of developing an allergic reaction and to help reduce other side effects.
Tiredness and a general feeling of weakness. It is important to allow yourself plenty of time to rest.
Fluid retention. You may notice that you gain weight and/or that your ankles and legs swell. This decreases slowly once your treatment has finished. Sometimes drugs can be given before you receive docetaxel to limit the fluid retention.
Less common side effects
Numbness or tingling in hands or feet. This is due to the effect of docetaxel on nerves. You may also notice that you have difficulty doing up buttons or other fiddly tasks. Tell your doctor if you notice any numbness or tingling in your hands or feet. This usually improves slowly a few months after the treatment is finished.
Changes in nails. The colour of your nails may change. This change grows out over several months once the treatment has finished. Pain in the nail bed may occur, but this is rare.
Pain in the joints or muscles. It is important to tell your doctor about this so that appropriate painkillers can be prescribed.
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MEDLINE SEARCH
1: J Clin Oncol 2003 Jan 1;21(1):123-8
Weekly high-dose calcitriol and docetaxel in metastatic androgen-independent prostate cancer.
Beer TM, Eilers KM, Garzotto M, Egorin MJ, Lowe BA, Henner WD.
Oregon Health & Science University and Portland VA Medical Center, Portland, OR 97239, USA. support@ohsuedu
PURPOSE: To determine the safety and efficacy of weekly high-dose oral calcitriol (Rocaltrol, Roche Pharmaceuticals, Basel, Switzerland) and docetaxel (Taxotere, Aventis Pharmaceuticals, Bridgewater, NJ) in patients with metastatic androgen-independent prostate cancer (AIPC). PATIENTS AND METHODS: Thirty-seven patients were treated with oral calcitriol (0.5 micro g/kg) on day 1 followed by docetaxel (36 mg/m(2)) on day 2, repeated weekly for 6 weeks of an 8-week cycle. Patients maintained a reduced calcium diet and increased oral hydration. Prostate-specific antigen (PSA) response was the primary end point, which was defined as a 50% reduction in PSA level confirmed 4 weeks later. RESULTS: Thirty of 37 patients (81%; 95% confidence interval [CI], 68% to 94%) achieved a PSA response. Twenty-two patients (59%; 95% CI, 43% to 75%) had a confirmed > 75% reduction in PSA. Eight of the 15 patients with measurable disease (53%; 95% CI, 27% to 79%) had a confirmed partial response. Median time to progression was 11.4 months (95% CI, 8.7 to 14 months), and median survival was 19.5 months (95% CI, 15.3 months to incalculable). Overall survival at 1 year was 89% (95% CI, 74% to 95%). Treatment-related toxicity was generally similar to that expected with single-agent docetaxel. Pharmacokinetics of either calcitriol or docetaxel were not affected by the presence of its companion drug in an exploratory substudy. CONCLUSION: The combination of weekly oral high-dose calcitriol and weekly docetaxel is a well-tolerated regimen for AIPC. PSA and measurable disease response rates as well as time to progression and survival are promising when compared with contemporary phase II studies of single-agent docetaxel in AIPC.
Further study of this regimen is warranted.
Publication Types: Clinical Trial Clinical Trial, Phase II
PMID: 12506180 [PubMed - indexed for MEDLINE]
2: Nippon Rinsho 2002 Dec;60 Suppl 11:266-71
[Therapy for hormone-refractory prostate cancer] [Article in Japanese]
Nishimura K, Takahara S, Nonomura N, Okuyama A., Department of Urology, Graduate School of Medicine, Osaka University.
Publication Types: Review Review, Tutorial
PMID: 12599583 [PubMed - indexed for MEDLINE]
3: Nippon Rinsho 2002 Dec;60 Suppl 11:205-10
[Chemotherapy for prostate cancers]
[Article in Japanese]
Naito K.
Department of Specific Organ Medicine, Yamaguchi University School of Medicine.
Publication Types: Review Review, Tutorial
PMID: 12599572 [PubMed - indexed for MEDLINE]
4: Urology 2002 Dec;60(6):1111
Fatal respiratory failure associated with treatment of prostate cancer using docetaxel and estramustine.
Morris MJ, Santamauro J, Shia J, Schwartz L, Vander Els N, Kelly K, Scher H.
Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Cornell University Weill Medical College, New York, New York, USA.
Chemotherapy that targets microtubular trafficking induces responses in most patients with prostate cancer. One regimen under investigation is the combination of docetaxel and estramustine. We report on 2 patients with androgen-independent disease who received continuous weekly docetaxel and estramustine and who died of irreversible respiratory failure. The clinical, pathologic, and radiographic data support drug toxicity as the likely etiology. Inclusive of these patients, only 17 cases (10 fatal) of acute pulmonary toxicity using docetaxel have been reported, despite its wide use. We recommend that patients receiving weekly docetaxel, with or without estramustine, have frequent treatment breaks and be evaluated with computed tomography of the chest every 8 weeks.
Publication Types: Review Review of Reported Cases
MID: 12475686 [PubMed - indexed for MEDLINE]
5: Australas J Dermatol 2002 Nov;43(4):293-6
Docetaxel-induced nail dystrophy.
Nicolopoulos J, Howard A.
Department of Dermatology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
A 73-year-old man with metastatic prostate cancer treated with weekly docetaxel chemotherapy for 5 months developed an acute nail dystrophy restricted to the fingernails. This was characterized by onycholysis, subungual haemorrhage and acute paronychia, progressing to a subungual abscess of the right index finger. Nail bed hyperaemia and haemosiderin-like nail bed discoloration were present. Nail plate avulsion was performed to decompress the acutely painful subungual abscess. The right thumb, middle finger and left index finger demonstrated early, proximal white subungual collections of pus obscuring the lunula (onychophosis). Central nail plate fenestrations with a surgical drill led to exudation of purulent material. Cultures of the subungual abscess material yielded mixed organisms, possibly related to administration of flucloxacillin for 1 week prior to presentation. The patient completed a further two courses of docetaxel without sequelae, and the nail dystrophy appears to be resolving. Docetaxel-induced nail changes are a common adverse effect, occurring in 30-40% of patients. Mild changes do not usually warrant the discontinuation of treatment.
Publication Types: Review Review of Reported Cases
PMID: 12423438 [PubMed - indexed for MEDLINE]
6: Cancer Res 2002 Oct 15;62(20):5720-6
Inhibition of growth and metastasis of orthotopic human prostate cancer in athymic mice by combination therapy with pegylated interferon-alpha-2b and docetaxel.
Huang SF, Kim SJ, Lee AT, Karashima T, Bucana C, Kedar D, Sweeney P, Mian B, Fan D, Shepherd D, Fidler IJ, Dinney CP, Killion JJ.
Department of Urology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
We evaluated whether treatment of orthotopic human prostate cancer in nude mice with pegylated IFN-alpha-2b (PEG-IFN-alpha-2b) and docetaxel could represent a two-compartment targeting of primary tumor (tumor cells and tumor-associated endothelial cells) and inhibition of regional lymph node metastasis. The antiangiogenic properties of IFN were combined with the cytotoxic properties of docetaxel, resulting in apoptosis of both tumor cells and endothelium and hence significant inhibition of primary tumor growth. We first determined the optimal biological dose of PEG-IFN-alpha-2b (70,000 IU/week) necessary to down-regulate the expression of basic fibroblast growth factor, matrix metalloprotease-9, and matrix metalloprotease-2. The therapeutic dose of docetaxel (10 mg/kg/week) was determined by efficacy and minimal body weight loss. Therapy beginning 3 days after orthotopic implantation of PC3-MM2 prostate cancer cells reduced tumor weight by 37% in mice treated with PEG-IFN-alpha-2b, by 60% in mice treated with docetaxel, and by 83% in those given both drugs. PEG-IFN-alpha-2b also induced apoptosis of tumor-associated endothelial cells and hence a significant decrease in microvessel density. Our data indicate that the combination of PEG-IFN-alpha and docetaxel inhibits neoplastic angiogenesis by inducing a decrease in the local production of proangiogenic molecules by tumor cells, resulting in increased apoptosis of tumor-associated endothelial cells.
Publication Types: Evaluation Studies
PMID: 12384530 [PubMed - indexed for MEDLINE]
7: J Urol 2002 Oct;168(4 Pt 1):1496
Prompt resolution of acute disseminated intravascular coagulation with docetaxel and cisplatin in hormone refractory prostate cancer.
Avances C, Jacot W, Senesse P, Culine S.
Department of Medical Oncology, CRLC Val d'Aurelle, Montpellier, France.
PMID: 12352431 [PubMed - indexed for MEDLINE]
8: Semin Urol Oncol 2002 Aug;20(3 Suppl 1):1-3
Editorial: the coming revolution in the treatment of prostate cancer patients.
Petrylak DP, de Wit R.
Publication Types: Editorial
PMID: 12198631 [PubMed - indexed for MEDLINE]
9: Semin Urol Oncol 2002 Aug;20(3 Suppl 1):31-5
Chemotherapy for androgen-independent prostate cancer.
Petrylak DP.
College of Physicians and Surgeons of Columbia University, Columbia-Presbyterian Medical Center, New York, NY 10032-3789, USA.
While men with metastatic prostate cancer frequently show a good initial response to androgen ablation, few options have been available for progressive hormone-refractory prostate cancer, and survival following chemotherapy has not exceeded 9 to 12 months. The combination of prednisone and mitoxantrone has significant palliative effects on bone pain but does not extend survival. The combination of estramustine phosphate (EMP) with the taxanes paclitaxel or docetaxel produces greater than additive cytotoxicity in vivo, and phase I and II studies of taxane-based therapy demonstrate improved survival in hormone-refractory prostate cancer compared to historical controls. Docetaxel appears to have relatively high activity as a single agent and in combination with EMP. Further studies are needed to clarify the optimum dose of EMP, taking into account potential cardiovascular toxicity. Phase III studies of its combination with docetaxel are in progress. Copyright 2002, Elsevier Science (USA). All rights reserved.
Publication Types: Review Review Literature
PMID: 12198636 [PubMed - indexed for MEDLINE]
10: Cancer Res 2002 Jul 1;62(13):3743-50
Identification of human uroplakin II promoter and its use in the construction of CG8840, a urothelium-specific adenovirus variant that eliminates established bladder tumors in combination with docetaxel.
Zhang J, Ramesh N, Chen Y, Li Y, Dilley J, Working P, Yu DC.
Cell Genesys, Inc., Foster City, California 94404, USA.
Uroplakins (UPs) are a group of integral membrane proteins that are synthesized as the major differentiation products of mammalian urothelium. UPII gene expression is bladder specific and differentiation dependent, but very little is known about its transcription response elements. To identify the promoter elements, a DNA fragment of 2239 bp upstream of the UPII gene was amplified by PCR and linked to a promoterless firefly luciferase reporter gene. Transient transfection experiments showed that the DNA segment located between -1809 and +1 bp resulted in preferential expression in bladder carcinoma cells with negligible expression in nonurothelial cells. This promoter was engineered into adenovirus (Ad) type 5 to drive the expression of the E1A and E1B genes and to create an attenuated replication-competent Ad variant, termed CG8840. Viral replication and the cytopathic effect of CG8840 were evaluated by virus yield and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays in bladder transitional cell carcinoma (TCC) cell lines RT4 and SW780; nonbladder cancer cell lines G361 (melanoma), LNCaP (prostate cancer), PA-1 (ovarian cancer), and U118 (brain cancer); and human primary cells including lung fibroblasts, bladder smooth muscle cells, and mammary epithelial cells. CG8840 replicated in and eliminated bladder TCC efficiently with high specificity (10,000:1) in comparison with nonbladder cells. The antitumor activity of CG8840 was examined in BALB/c nu/nu mice carrying s.c. human TCC xenografts. Intratumoral and i.v. administration of CG8840 in RT4 human bladder cancer xenografts caused significant (P < 0.01) inhibition of tumor growth. Synergistic antitumor efficacy was observed when CG8840 was combined with docetaxel, resulting in significant regression of RT4 bladder cancer xenograft tumors within 6 weeks after i.v. administration of CG8840 (3.33 x 10(9) plaque-forming units/animal on day 1) and docetaxel (20 mg/kg on days 2, 6, and 9). These results demonstrate the utility of the UPII promoter in the generation of urothelium-specific adenoviral vectors and provide a potential foundation for the development of bladder tumor-specific oncolytic viral therapies.
PMID: 12097284 [PubMed - indexed for MEDLINE]
11: Cell Mol Life Sci 2002 Jul;59(7):1198-211
Survival of docetaxel-resistant prostate cancer cells in vitro depends on phenotype alterations and continuity of drug exposure.
Makarovskiy AN, Siryaporn E, Hixson DC, Akerley W.
Department of Medical Oncology, Rhode Island Hospital/Brown University School of Medicine, Providence 02903, USA.
We evaluated in vitro the effect of paclitaxel and docetaxel on PC-3 and DU-145 prostate cancer cell lines to understand better the downstream events in drug-induced tumor cell death. Taxane treatments of DU-145 cells induced rapid cell death by apoptosis, but in PC-3 cells, treatments achieved growth arrest, followed by extensive karyokinesis resulting in multinucleation, giant-cell formation and delayed cell death. To determine if the giant multinucleated cells were able to produce proliferating and drug-resistant survivors, we first delineated the kinetics of drug activity and cytotoxic dose range. Analysis of both lines by colorimetric and cell viability assays demonstrated improved cytotoxicity of taxanes applied continuously. Selected doses and schedules of docetaxel were used to induce giant multinucleated cells that gave rise to docetaxel-resistant survivors, which remained sensitive to paclitaxel and other chemotherapeutics. Growth and morphology of the recovered clones was similar to parental cells. The resistant phenotype of these clones determined by immunofluorescence and immunoblot was associated with transient expression of the beta-tubulin i.v. isoform and was independent of P-glycoprotein, bcl-2 and bcl-xL. Resistant clones will be useful to model progression of resistance to taxanes and to identify unknown and clinically important molecular mechanisms of cell death and resistance.
PMID: 12222966 [PubMed - indexed for MEDLINE]
12: Can J Urol 2002 Jun;9 Suppl 1:21-5
The role of chemotherapy in advanced prostate cancer.
Ernst DS.
Department of Medicine, Tom Baker Cancer Centre, Calgary, Alberta, Canada.
The development of hormone resistance is an unfortunate final common pathway in most patients with advanced prostate cancer, resulting in a narrowing of therapeutic options for the clinician, and limited median survival of 10-12 months for the patient. While cytotoxic chemotherapy has been utilized for many years, its efficacy has been disappointing. Quality of life assessments are increasingly used in assessing response in hormone-resistant prostate cancer (HRPC), and PSA has emerged as an important surrogate marker of response in both local and advanced disease. Estramustine and the taxanes have been investigated, as monotherapy and in combination, in the treatment of HRPC in phase 2 and 3 clinical trials, a number of which are ongoing. Substantial advances in the management of HRPC over the past decade have led to renewed optimism that improvement in survival can be achieved, and support the belief that chemotherapy plays a role in this pursuit. In tandem with the development of new agents, refined means of assessing response have been developed, and represent a key component of new research strategies in HRPC.
Publication Types: Review Review, Tutorial
PMID: 12121591 [PubMed - indexed for MEDLINE]
13: Curr Urol Rep 2002 Jun;3(3):232-8
Effects of docetaxel on pain due to metastatic androgen-independent prostate cancer.
Beer TM, Bubalo JS.
Department of Medicine, Oregon Health & Science University, Mail Code L586, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA.
support@ohsuedu
Bone pain commonly plagues patients with metastatic androgen-independent prostate cancer. Studies of mitoxantrone demonstrated that chemotherapy can substantially reduce this debilitating symptom. Two of the available studies examining the use of docetaxel with and without estramustine for treatment of androgen-independent prostate cancer include a detailed prospective analysis of pain and quality of life. One study required patients to have pain at entry and demonstrated significant improvement in pain. The second study enrolled patients with low prevalence and intensity of pain and did not demonstrate pain relief. The available results, although preliminary, suggest that patients with significant bone pain due to androgen-independent prostate cancer can experience substantial pain relief with docetaxel-based therapy. Larger randomized studies targeting patients with sufficient prevalence and intensity of pain are needed to refine our understanding of the contribution of docetaxel to pain control in this patient population.
Publication Types: Review Review, Tutorial
PMID: 12084194 [PubMed - indexed for MEDLINE]
14: Oncology (Huntingt) 2002 Jun;16(6 Suppl 6):63-72
Docetaxel in the integrated management of prostate cancer. Current applications and future promise.
Logothetis CJ.
Department of Genitourinary Medical Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
support@mail.mdandersonorg
Docetaxel (Taxotere)-based regimens can be included among the most effective treatment options for the management of patients with advanced, androgen-independent prostate cancer. Results with docetaxel as a single agent and in combination regimens with estramustine (Emcyt) have consistently achieved a palliative response, reduced serum PSA levels by > or = 50%, and produced objective responses in patients with measurable disease. In addition, encouraging survival data have been demonstrated in several phase II trials. The ability to administer docetaxel on a weekly basis has substantially enhanced research efforts for treatment in prostate cancer patients. The results of ongoing phase III randomized trials evaluating docetaxel regimens in androgen-independent prostate cancer are eagerly awaited for their potential to definitively demonstrate a beneficial impact on overall patient survival. Docetaxel-containing regimens are likely to demonstrate a substantial role in the management of early-stage prostate cancer patients in the adjuvant and neoadjuvant settings, where clinical investigations are under way. In addition, study results from ongoing trials that integrate docetaxel with hormonal therapies for patients with biochemical recurrence following definitive local treatments will be important in refining the future role of chemotherapy for prostate cancer in general. The preliminary findings from studies conducted with docetaxel are encouraging and await final analysis. Finally, preliminary results from studies exploring combination regimens of docetaxel and novel agents that possess completely different mechanisms of action (eg, proapoptotic agents, angiogenesis inhibitors, and vitamin D analogs) have demonstrated the regimens to be feasible and safe, with promising early response data. These types of investigational studies will likely occupy a dominant position in future research initiatives for patients with advanced prostate cancer.
Publication Types: Review Review Literature
PMID: 12108899 [PubMed - indexed for MEDLINE]
15: Neoplasia 2002 May-Jun;4(3):255-62
Early response of prostate carcinoma xenografts to docetaxel chemotherapy monitored with diffusion MRI.
Jennings D, Hatton BN, Guo J, Galons JP, Trouard TP, Raghunand N, Marshall J, Gillies RJ.
Department of Biochemistry, University of Arizona Health Sciences Center, 1501 North Campbell Avenue, Tucson, AZ 85724, USA.
For many anticancer therapies, it would be desirable to accurately monitor and quantify tumor response early in the treatment regimen. This would allow oncologists to continue effective therapies or discontinue ineffective therapies early in the course of treatment, and hence, reduce morbidity. This is especially true for second-line therapies, which have reduced response rates and increased toxicities. Previous works by others and ourselves have shown that water mobility, measured by diffusion-weighted magnetic resonance imaging (DW-MRI), increases early in tumors destined to respond to therapies. In the current communication, we further characterize the utility of DW-MRI to predict response of prostate cancer xenografts to docetaxel in SCID mice in a preclinical setting. The current data illustrate that tumor volumes and secreted prostate-specific antigen both respond strongly to docetaxel in a dose-responsive manner, and the apparent diffusion coefficient of water (ADC(w)) increases significantly by 2 days even at the lowest doses (10 mg/kg). The ADCw data were parsed by histogram analyses. Our results indicate that DW-MRI can be used for early detection of prostate carcinoma xenograft response to docetaxel chemotherapy.
PMID: 11988845 [PubMed - indexed for MEDLINE]
16: Cancer 2002 Mar 1;94(5):1457-65
Phase II evaluation of docetaxel plus one-day oral estramustine phosphate in the treatment of patients with androgen independent prostate carcinoma.
Sinibaldi VJ, Carducci MA, Moore-Cooper S, Laufer M, Zahurak M, Eisenberger MA.
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
support@jhmiedu
BACKGROUND: Recent clinical trials have shown antitumor activity with the combination of docetaxel plus estramustine phosphate (EMP) in the treatment of patients with androgen independent prostate carcinoma (AIPC). However, the most commonly employed treatment schedules with EMP have been associated with significant gastrointestinal, cardiovascular, and thromboembolic toxicity. The authors hypothesized that the therapeutic index of the combination of docetaxel plus EMP for patients with prostate carcinoma could be enhanced by reducing the incidence and severity of EMP-associated toxicity, which could be accomplished by shortening the duration of exposure to EMP. To preserve the therapeutic synergism between docetaxel and EMP, they designed a regimen employing higher doses of oral EMP administered on the day of the docetaxel infusion. METHODS: From June 1, 1998 through September 28, 2000, 42 patients with AIPC were registered to receive docetaxel (70 mg/m2 intravenously over 1 hour) and EMP (280 mg orally every 6 hours x 5 doses) every 21 days, up to a maximum of 6 cycles. Dexamethasone was administered prior to docetaxel and coumadin 2 mg orally every day was taken during the study treatment period. Patient characteristics included a median age of 68 years, a median Eastern Cooperative Oncology Group performance status of 1, a median prostate specific antigen (PSA) level at study entry of 110.5 ng/mL, and a median of 2 prior hormonal manipulations. Ten patients (25%) had received prior chemotherapy, and 14 patients (33%) had received prior palliative radiation therapy.
RESULTS: Forty patients were evaluable for response and toxicity. Eighteen patients (45%; 95% confidence interval, 29-62%) had a decline > 50% in PSA level that lasted > 4 weeks with a median time to PSA progression and a median duration of PSA response of approximately 4.0 months. Four of 20 patients (20%) had partial soft tissue responses. Ten of 17 symptomatic patients (59%) had improvement in pain. The median survival for all patients was 13.5 months. The most prominent Grade 3 and 4 toxicities were reversible myelosuppression and fatigue. Nausea, emesis, diarrhea, and peripheral edema were minimal. No thromboembolic or hepatic complications were seen. CONCLUSIONS: Docetaxel plus 1 multidose day of oral EMP was active in patients with AIPC and was associated with an acceptable toxicity profile. Overall, the therapeutic index of this regimen compared favorably with regimens that employed a longer administration of EMP. Copyright 2002 American Cancer Society.
Publication Types: Clinical Trial Clinical Trial, Phase II
PMID: 11920502 [PubMed - indexed for MEDLINE]
17: Cancer 2002 Feb 1;94(3):847-53
Severe interstitial pneumonitis associated with docetaxel administration.
Read WL, Mortimer JE, Picus J.
Department of Medicine, Division of Medical Oncology at Washington University, St. Louis, Missouri, USA.
support@medicine.wustledu
BACKGROUND: Interstitial pneumonitis has not been reported as a toxicity of docetaxel. The authors report the presentation and natural history of four patients who developed a severe interstitial pneumonitis after receiving docetaxel. METHODS: The hospital and outpatient records of patients treated with docetaxel were reviewed to identify whether any of these patients required an evaluation for respiratory problems.
RESULTS: Four patients developed an interstitial pneumonitis that could be explained only as a toxicity of docetaxel. None had metastatic disease to the lung, and all had normal liver function before receiving chemotherapy. The patients presented with acute dyspnea and fever within 1-2 weeks of receiving docetaxel. All developed progressive interstitial infiltrates and respiratory failure that required mechanical ventilation. An exhaustive workup for other causes of pneumonitis was negative. Broad-spectrum antibiotics and corticosteroids were ineffective. Two patients died of complications related to the pulmonary process. The two survivors required ventilatory support for more than 21 days. The clinical and pathologic findings of these patients are presented. CONCLUSIONS: Interstitial pneumonitis is a rare and potentially fatal complication of docetaxel treatment. Prolonged ventilatory support is appropriate in patients with a favorable prognosis.
Copyright 2002 American Cancer Society. DOI 10.1002/cncr.10263
PMID: 11857321 [PubMed - indexed for MEDLINE]
18: Front Radiat Ther Oncol 2002;36:72-80
Controversies in chemotherapy of prostate cancer.
Heicappell R.
Department of Urology, Universitatsklinikum Benjamin Franklin, Freie Universitat, Berlin, Germany.
support@medizin.fu-berlinde
Publication Types: Review Review, Tutorial
PMID: 11842757 [PubMed - indexed for MEDLINE]
19: J Urol 2002 Jan;167(1):339-46
Enhanced transgene expression in androgen independent prostate cancer gene therapy by taxane chemotherapeutic agents.
Li Y, Okegawa T, Lombardi DP, Frenkel EP, Hsieh JT.
Department of Urology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9110, USA.
PURPOSE: Chemotherapy is often used as a primary therapy for metastatic cancer because it kills cells en masse. However, high doses of chemotherapeutic drugs can cause toxicity in nontarget organs. Gene therapy may provide a better alternative to chemotherapy because its targeting of specific genes may reduce the undesirable toxicity associated with chemotherapy. We evaluated whether the chemotherapeutic agent docetaxel or paclitaxel may be combined with gene therapy to create a new therapeutic regimen for metastatic androgen independent prostate cancer. MATERIALS AND METHODS: The 2 androgen independent prostate cancer cell lines PC-3 and DU 145 were treated with docetaxel or paclitaxel. Three recombinant adenoviruses containing p21WAF-1/CIP1, p53 protein or beta-galactosidase complementary DNA under the control of cytomegalovirus promoter were used to determine transgene expression. They were evaluated by Western blot analysis, beta-galactosidase activity or in vitro growth assays. The [(3)H] labeled E1 deleted adenovirus dl312 was used to determine adenovirus uptake into cells.
RESULTS: Docetaxel and paclitaxel enhanced adenovirus mediated transgene expression. Docetaxel appears to be a more potent growth inhibitor in vitro. Elevated transgene expression in virus infected cells induced by these 2 drugs was produced by increased cytomegalovirus promoter activity rather than increased virus uptake. CONCLUSIONS: The potential synergy of gene therapy with docetaxel and paclitaxel may be an important direction for future therapy for metastatic androgen independent prostate cancer.
PMID: 11743353 [PubMed - indexed for MEDLINE]
20: Prostate 2002 Jan 1;50(1):27-37
Combined modality radioimmunotherapy for human prostate cancer xenografts with taxanes and 90yttrium-DOTA-peptide-ChL6.
O'Donnell RT, DeNardo SJ, Miers LA, Lamborn KR, Kukis DL, DeNardo GL, Meyers FJ.
Department of Internal Medicine, Division of Hematology and Oncology, Section of Radiodiagnosis & Therapy, University of California Davis Medical Center, Sacramento, California 95816, USA.
support@ucdavisedu
BACKGROUND: Therapy for prostate cancer in the PC3 tumor-nude mouse model with 90yttrium-(90Y)-DOTA-peptide-ChL6 (5.55 MBq;150 microCi) has resulted in durable responses. To make radioimmunotherapy (RIT) more effective, the radiation-enhancing drugs Taxol (paclitaxel) and Taxotere (docetaxel) were tested for synergy with 90Y-DOTA-peptide-ChL6.
METHODS: Nude mice bearing human prostate cancer PC3 xenografts were treated with 90Y-DOTA-peptide-ChL6 (2.78 MBq; 75 microCi) and after 24 hr, paclitaxel (300 or 600 microg), or docetaxel (300 microg). Tumor size, survival, blood counts, and pharmacokinetics were monitored to assess efficacy and toxicity. RESULTS: Docetaxel plus RIT had a 67% cure rate, whereas no mice were cured among the RIT alone, chemotherapy alone, or untreated controls. Paclitaxel (600 microg) plus RIT produced a 100% response rate with 20% cures. Average tumor volume was reduced to a greater degree in the combined modality radioimmunotherapy (CMRIT) groups compared to controls and the anti-tumor response was durable. Myelotoxicity in the combined modality groups (RIT plus paclitaxel or RIT plus docetaxel) were similar to groups receiving the same dose of RIT alone.
CONCLUSION: In the PC3-tumor nude mouse model, addition of paclitaxel or docetaxel to 90Y-DOTA-peptide-ChL6, in doses clinically achievable in humans, provided therapeutic synergy without increased or excessive toxicity. Copyright 2002 Wiley-Liss, Inc.
PMID: 11757033 [PubMed - indexed for MEDLINE]
21: Urology 2002 Jan;59(1):137, Successful treatment of metastatic hormone-refractory prostate cancer with malignant pericardial tamponade using docetaxel.
Hayes-Lattin BM, Kovach PA, Henner WD, Beer TM.
Oregon Health and Science University, Portland, Oregon 97201, USA.
Reports of malignant pericardial effusion due to adenocarcinoma of the prostate are few and describe only patients with hormone-naive disease. We report a case of malignant pleural and pericardial effusions due to metastatic hormone-refractory prostate cancer. Despite presenting with pericardial tamponade, this patient was successfully treated with pericardiocentesis and intrapericardial methylprednisolone and cisplatin, followed by a course of intravenous docetaxel. The patient was alive and free of disease-related symptoms nearly 2 years later. This case suggests that patients with pericardial tamponade due to hormone-refractory prostate cancer do not have a uniformly dismal prognosis and should be considered for aggressive treatment.
PMID: 11796304 [PubMed - indexed for MEDLINE]
22: Tumori 2001 Nov-Dec;87(6):A12-4 [Chemotherapy of prostate cancer: potential role of docetaxel]
[Article in Italian]
Bracarda S.
Publication Types: Review Review, Tutorial
Hans J LL legte am 25.5.2005 die folgende Übersetzung vor:
Nutzen einer Chemotherapie
Charles E. Myers [ein amerikanischer Onkologe und Experte für Prostatakrebs – Ed] hat eine Präsentation für die Prostate Center Support Group am Kettering Medical Center gehalten. (25. April 2002) Hier einige Ausschnitte übersetzt:
Erstmals habe ich 1987 an dieser Krankheit gearbeitet. Während der ersten fünf Jahre meiner Arbeit am PK war die übereinstimmende Meinung, dass man vom Beginn der Hormonrefraktion noch 6 bis 8 Monate zu leben hatte.
Nun muss ich Ihnen aber sagen, dass ich mich nicht an das letzte Mal erinnern kann, wo ich einen Patienten gesehen habe, der nach weniger als einem Jahr gestorben ist, nachdem er hormonrefraktär wurde. Meistens waren es zwei Jahre, vielleicht auch länger. Und ich glaube, es lassen sich bei weitem bessere Ergebnisse erzielen.
Ich war bei einem Meeting in West Palm Beach, wo einer der jungen Forscher von M.D. Anderson die Ergebnisse der neuesten klinischen Tests präsentierte. Es wurde kein spezifisches Medikament herausgestellt, jedoch gesagt, dass der Median der Überlebenszeit bei all ihren Versuchen mit hormonrefraktärem PK bei 36 Monaten lag. Und dass sie nur Männer mit weit verbreiteten Metastasen zu sehen bekommen, die schlimmste Art von PK also, bei solchen Versuchen. Es gibt viele Männer mit hormonrefraktärem Krebs, der viel langsamer wächst, und besser sein kann als diese Zahlen es hergeben.
Ich habe einen Patienten, der 1994 hormonrefraktär wurde. Er bekam eine Chemo, die acht Wochen dauerte, und dann nahm er die Medikamente, die wir ihm zum Stoppen des Wachstums seiner Krankheit verschrieben. Sein Krebs blieb bis 2001 unter Kontrolle. Er musste wieder eine Chemo durchmachen. Er hat wieder Unterdrückungstherapie und hat während der letzten zwei Jahre südlich von Santa Barbara ein größeres Weingut aufgebaut.
Was ich besonders bekämpfen will, ist dieses überwältigende negative Gefühl, das Männer bekommen, wenn sie die Diagnose hormonrefraktär bekommen, oder das von ihren Ärzten rüberkommt, nur weil die Ärzte bei hormonrefraktärer Lage ihre Möglichkeiten einfach nicht kennen.
Und natürlich, wenn Ihr Verstand nicht positiv denkt, und Sie marschieren nicht los und erledigen, was getan werden kann, dann kriegen Sie natürlich ein schlechtes Resultat. Wie Sie wissen, ein Pessimist bekommt immer die Bestätigung für seine schlimmsten Befürchtungen, während die unerwartet guten Sachen den Optimisten passieren. Also, was hat sich beim hormonrefraktären PK getan?
Erstens haben wir jetzt eine ganze Gruppe von Medikamenten-Kombinationen, auf die mehr als die Hälfte der Patienten ansprechen. Und mit Ansprechen meine ich, dass ihr PSA um mehr als 50 % zurückgeht. Jetzt können Sie sagen: Wie wichtig ist es, dass mein PSA um 50% fällt? Nun, in jedem Krebszentrum, das sich hiermit beschäftigt, wo alle Medikamentenkombinationen genutzt werden, übersetzt man einen 50-prozentigen Abfall Ihres PSA mit zwei Jahre Überleben. Deshalb sterben die Männer jetzt nicht mehr nach sieben bis acht Monaten.
„Wenn Sie sagen: 50 % Ansprechrate, bedeutet das doch, dass ich nur 50:50-Chance habe?“ Aber nein, das hat mir Ken Pienta von der Universität Michigan erklärt, als er seine PK-Patienten durchsprach. Er sagte: Während nur 50 % auf diese Kombination ansprechen, haben wir doch drei oder vier Kombinationen, und man probiert sie nacheinander durch, und dann sprechen 95 % der Patienten auf eine dieser Kombinationen an. So können wir fast jeden Mann mit hormonrefraktärem PK zum Ansprechen auf Chemo bringen. Es kann also sein, das wir es beim ersten Mal nicht gleich hinkriegen.
Und dann muss man noch etwas verstehen. Chemotherapie verursacht gewöhnlich ein Anfangsansprache. Über die ersten 2 bis 3 Monate fällt der PSA und die Tumormassen gehen zurück, und dann bildet sich ein Plateau aus. Man kann mit der Chemo weitermachen, aber es wird dadurch keinen Deut besser. Ich meine, der Zeitpunkt zum Aufhören mit der Chemo ist dann erreicht, wenn wir einen Deckel drauf halten können. Der erste, der gezeigt hat, dass dies ein kluges Vorgehen ist, war Dan Petrylak von der Universität von Columbia. Er beschäftigte sich mit Taxotere, einem der Medikamente, die wir benutzen. Nach den ersten 3 bis 4 Monaten, wenn das Ansprechen zur Plateaubildung überging, hörte er mit der Behandlung auf. Er hatte herausgefunden, dass er nach weiteren 3 bis 4 Monaten mit der Behandlung wieder einsetzen konnte, und der Patient sprach auf genau dasselbe Medikament an und kam wieder ein Plateau herunter. Stop. Ein paar Monate warten und dasselbe wiederholen. Es ist, als ob der Widerstand nur eine bestimmte Zeit dauert und nach 3 oder 4 Monaten Chemotherapie-Pause verschwindet.
Was nun einige versuchen, und ich bin wirklich nicht der einzige, ist den PSA mit der Chemotherapie um 50 bis 90 % zu senken, und dann aufzuhören, - aber nicht um nichts zu tun, sondern die Männer auf Medikamente zu setzen, die das Wachstum dieses Krebses verlangsamen. Bei einer Anzahl meiner Patienten bringen wir so den PSA bei einem Ausgangswert von sagen wir 200 hinunter auf 80, wo sich ein Plateau bildet. Setze sie auf Medikation, die das Wachstum des Krebses behindert und nach drei Monaten ist das PSA vielleicht von 80 auf 100 gegangen. Zurück zur Chemotherapie und sie gehen von 100 auf 30. Am Ende haben sie sich so eine Treppe hinunterbewegt, und natürlich ist das Ziel ein unmeßbares PSA und vollkommene Remission zu erreichen. Eine Anzahl von Onkologen wenden diese Methode in den USA an. Schon jetzt kann ich sagen dass die Lebensqualität viel, viel besser ist, wenn man Urlaub von der Chemo nehmen kann. Wer von Ihnen schon mal auf Chemotherapie war, weiß wie schön ein solcher Urlaub ist.
Inzwischen hat sich noch einiges andere ergeben: Zometa ist ein Medikament, das den Krebs daran hindert, die Knochen zu zerstören. Es ist das stärkste Medikament in dieser Serie. Die anderen sind z. B. Actonel, Fosamax, Aredia. Zometa ist das beste dieser Gruppe. Die klinischen Tests haben ergeben, dass bei PK mit Knochenmetastasen Zometa Ihr Risiko neuer Knochenmetastasen über mehrere Jahre dramatisch absenkt. Deshalb ist dies ein weiteres sehr nützliches Werkzeug, den Fortschritt der Krankheit zu verhindern und zwar ohne die Nebenwirkungen der Chemotherapie.
Wiederum treten Fehler auf, wenn der Onkologe versucht, diese Krankheit stückweise anzugehen und sich ein einzelnes Werkzeug herauspickt. Das ist wie wenn man Schwimmen geht und das Wasser ist kalt, man steckt den großen Zeh rein, dann geht man langsam nach und nach rein, wie weh das tut. Wenn Sie diese Methodik auf Chemotherapie und hormonresistenten PK anwenden, dann muss man eher vom Sprungbrett voll in den kalten See eintauchen. Sie müssen alle für diese Krankheit verfügbaren Werkzeuge zusammen gleichzeitig einsetzen und das in einer integrierten Art und Weise, bei der alle Phasen zusammenarbeiten müssen. Calcitriol, ein Medikament, über das wir Anfangs gesprochen haben, kommt jetzt zurück, um eine neue Rolle zu spielen. Ich glaube, der aufregendste Aufsatz der letzten zwei Jahre über Chemotherapie ist der von Dr. Beer von der Universität von Oregon. Er hat gezeigt, dass eine einzige massive Dosis Calcitriol, die 24 Stunden vor der Chemotherapie administriert wird, die Nebenwirkungen in keiner Weise verstärkt, aber die Anti-Tumor-Wirkung enorm verstärkt. Er beschäftigt sich spezifisch mit Taxotere, dem wirksamsten einzelnen chemotherapeutischen Medikament für PK. Die Ansprechrate ging im Labor von ca. 40 auf 75 %, die gleiche Methode verbessert dramatisch die Wirksamkeit von Carboplatin, ein weiteres Medikament in der Behandlung von PK. Eine Anzahl von Onkologen benutzt es. So kann man erkennen, wie all diese verschiedenen Werkzeuge plötzlich wirksamer werden, weil wir gelernt haben, besser mit ihnen umzugehen.
MichaelK schrieb am 12.1.2006:
In vielen Quellen habe ich relativ optimistische Aussagen über DHB bei lokalisiertem oder lokal fortgeschrittenem, nichtmetastatischem Prostatakrebs. Aber keine spezielle Aussagen über DHB bei fortgeschrittenem Prostatakrebs mit Metastasen.
Ich sehe zwar keine vernünftige Alternative zu DHB, aber es wäre trotzdem interessant, welche Infos es zu diesem Thema gibt, weil bei mir es gerade der Fall ist (Lymphknoten am Hals sind betroffen. Wo noch etwas steckt, zeigen die Untersuchungen, die ab nächster Woche beginnen).
Ralf antwortete am selben Tag:
Dr. Leibowitz fügt routinemäßig beim Vorliegen mindestens eines Hochrisikofaktors (PSA >20 ng/ml, GS >6, Vorliegen von Metastasen oder befallenen Lymphknoten) der DHB eine Vierfach-Chemotherapie hinzu, weil er die Erfahrung gemacht hat, dass bei allen den Patienten, bei denen die DHB nicht wunschgemäß wirkte, mindestens einer dieser Faktoren vorlag. Leider wirst Du in Deutschland keinen Arzt finden, der das nachmacht.
[Ralf bekam daraufhin direkte Post von Urologe fs, der schrieb:
"Das stimmt nicht ganz. Ich gebe zusätzlich low-dose-Taxotere von Anfang an, wenn der Pat. die Kosten übernimmt, denn bisher habe ich noch jede Bitte um Übernahme von den Kassen abgelehnt bekommen mit der Begründung – noch nicht nachgewiesen (Klinik rechts-der-Isar geht übrigens auch so vor). Ich kenne das Originalschema, welches mir durch Korrespondez mit Kollegen Tucker von ihm persönlich zugestellt wurde. Es wird bei mir unter bestimmten Umständen – allerdings in einer von mir modifizierten Variante – engesetzt. Ich hatte jetzt einen 50-jährigen Patienten mit kompletter Metastasierung aller Knochen und PSA 1035 ng/ml. Der ist unter diesem Regime gesten bei PSA 0,08 ng/ml - bezahlt das Taxotere allerdings selber. Ich habe gegeben: Low-dose-Taxotere 40 mg, zusammen mit dem Zometa alle vier Wochen. Estramustin 3 x 280 mg in den ersten drei Monaten kontinuierlich, CalciumD3, Rocaltrol 1 x abends, Selenase 2 x 1, Proscar 1 x 1, Androcur 2 x 2 (nach 6 Mon. auf Casodex umgestellt), Bion 3, Eligard, Fortecortin 1 mg. Ich habe in diesem Falle auf HDK verzichtet. Patient hat mit Viagra immer noch normal GV!]
Auf Anfrage ergänzte Ralf am 14.1.2006 seine obenstehende Antwort:
Die Vierfach-Chemo ist nachzulesen bei den KISP-Texten, Nrn. 38 und 62. Auszug aus Nr. 62:
"Derzeit besteht unsere Therapie der ersten Wahl bei metastatischer Erkrankung in der Verwendung von niedrig dosiertem, wöchentlichem Taxotere, Estramustin und Carboplatin. Wir haben eine Ansprechrate von über 90 %, definiert als PSA-Verringerung um 50 % oder mehr, wenn wir dieses Programm anwenden. Die überwiegende Mehrheit unserer Patienten haben einen vollständigen Rückgang aller Schmerzen, wenn vorhanden, innerhalb von ein oder zwei Dosen. Diese Form der Chemotherapie geht mit keiner der klassischen Nebenwirkungen von Chemotherapie wie Übelkeit, Erbrechen, Haarausfall, Infektionsrisiko oder der Notwendigkeit von Transfusionen einher. Diese Chemotherapie führt zu Müdigkeit, die dieser Patient bereits verspürt. Estramustin erhöht in der Tat das Risiko von Tiefvenenthrombose, und eine prophylaktische oder aktive Blutgerinnungshemmung ist erforderlich. Die spezifische Dosierung von Taxotere, Emcyt und Carboplatin ist wie folgt: Taxotere 25 mg/m², Carboplatin 200 mg insgesamt und Estramustin zwei Kapseln zu je 140 mg dreimal täglich, aber nur am Tag der Chemotherapie und am Tag danach. Dexamethason wird nur am Tag der Chemotherapie 20 mg intravenös und als 4-mg-Tablette am Morgen nach ihr verabreicht. Die Therapie wird an den Tagen 1, 8 und 15 eines 28-tägigen Zyklus verabreicht, und ich würde erwarten, dass der Patient etwa 12 bis 18 Chemotherapie-Dosen bekommen sollte, wenn er nach vier bis acht Wochen anspricht."
Die vier Hauptkomponenten sind also niedrig dosiertes Taxotere, Emcyt (Estracyt, Multosin), Carboplatin und Dexamethason, außerdem noch Diverses gegen etwaige Nebenwirkungen wie Thrombosen (durch das Estramustinphosphat), Übelkeit usw. Erfahrungen mit dieser Therapie kannst Du nachlesen im Forumextrakt - Therapieerfahrungen - Chemotherapie, ja, und auch in den "Texten", Nr. 14. Niemand, auch Leibowitz und Tucker nicht, behaupten, dass sie Wunderheiler sind, die jeden retten könnten.
Dine150 fragte am 3.12.2008:
Kann mir jemand erklären wie das bei einer Chemo abläuft? Er bekommt dann die Infusion und darf wieder nach Hause, nach ein paar Tagen geht es ihm superschlecht, er übergibt sich, ihm fallen die Haare aus und hat Schmerzen im ganzen Körper, danach hat er ein paar Wochen Pause und die ganze Sache geht von vorne los? Ich weiß, das alles muss auch nicht passieren, aber im schlimmsten und meisten Fällen läuft es doch so ab, oder? Was passiert dann? Bekommt er dann so lange er lebt Chemos bis der Körper schlapp macht, denn heilbar durch Chemo kommt ja auch nicht mehr in Frage?
Daniel Schmidt (Strahlentherapeut) antwortete:
Ich versuch's mal.
Zitat:
Er bekommt dann die Infusion und darf wieder nach Hause, nach ein paar Tagen, geht es ihm super schlecht, er übergibt sich, ihm fallen die Haare aus und hat Schmerzen im ganzen Körper, danach hat er ein paar Wochen Pause und die ganze Sache geht von vorne los?
Jein...
1. In der Regel sind es mehrere Infusionen bei Cisplatin+Etoposid, auf jeden Fall viel Flüssigkeit. Neben der Chemo, kriegt er noch Vor- und Nachwässerung für die Nieren und einige Medikamente, die die Nebenwirkungen der Chemotherapie lindern sollen.
Er bleibt in der Regel ein paar Tage im Krankenhaus, darf aber dann nach Hause. In der Regel wird Cisplatin+Etoposid stationär gemacht, es gibt Onkologen, die es aber auch ambulant machen.
2. Übelkeit kann es geben, Cisplatin verursacht dies gerne. Falls die Nierenwerte nicht so toll sind, kann es sein, dass man auf Carboplatin umsteigt. Diese Substanz macht nicht soviel Übelkeit. Erbrechen ist leider möglich, er wird aber Medikamente vorbeugend dafür bekommen.
3. Die Haare werden ausfallen, Etoposid verursacht diesen Effekt leider.
4. Schmerzen sollte er eigentlich wegen der Chemo nicht haben.
5. In der Regel macht man diese Chemotherapie alle drei bis vier Wochen, jeweils über ein paar Tage.
Zitat:
Ich weiß, das alles muss auch nicht passieren, aber im schlimmsten und meisten Fällen läuft es doch so ab, oder?
Was oft passiert ist, dass die Blutwerte abfallen und er dann Bluttransfusionen braucht. Es kann auch zu Infektionen mit Fieber kommen. Blutungen sind selten.
Zitat:
Was passiert dann? Bekommt er dann so lange er lebt Chemos bis der Körper schlapp macht, denn heilbar durch Chemo kommt ja auch nicht mehr in Frage?
Man macht in der Regel vier Zyklen dieser Chemo und beurteilt anschließend den Effekt. Ein ganzes Leben lang kann man diese natürlich nicht machen. Falls der Tumor schlecht ansprechen sollte, kann man auch ein anderes Schema ausprobieren, es nennt sich ACO.
Eine Heilung ist realistisch nicht zu erwarten, ein Überlebensgewinn (wenn der Tumor anspricht) schon.