Question on ketoconazole

I'd like to ask a question of those who have taken or are taking ketoconazole. How long does it take to take effect? I am concerned because after two months of use, my PSA has not come down significantly. I started the high dose of 400 mg three times a day two months ago when my PSA was 17. After one month, it came down to 12 and I was encouraged, thinking that maybe it just takes a while to reach nadir. Then a few days ago at the end of the second month, I had my PSA checked and it is back to 15. Is there something I am doing wrong?

[Johnstonearch]

It seems to be working just fine as long as you keep getting better numbers. I was on it for 8 years and it was very effective. The expert on this treatment is Dr. Myers on Charlottesville Virginia, you should pay him a visit.

[Hidden in reply to Johnstonearch]

Hi Johnstonearch,

Thanks for your very encouraging reply. Did you take keto right off the bat or was it after the failure of antiandrogens like Lupron, Casodex etc?

[Hidden]

I according to my Researcher Medical Oncologist, Ketoconazole does have Prostate Cancer killing properties. However, his research showed that it is best used in combination with other agents that also have Cancer killing properties. I took Keto every day for three cycles during a six month trial.

The combination therapy which I received was a part of a Clinical Trial and was as follows:

Each course of chemotherapy lasts for 8 weeks. Patients were treated in weeks 1, 3, and 5 with Doxorubicin 20 mg/m2 as a 24-hour intravenous infusion on the first day of every week in combination with Ketoconazole 400 mg orally 3 times a day daily for 7 days. In weeks 2, 4, and 6, treatment consisted of Paclitaxel 100 mg/m2 intravenously on the first day of every week in combination with Estramustine 280 mg orally 3 times a day for 7 days. During the 24 weeks 30 mg of Prednisone were taken orally in two doses, 10 mg and 20 g. Hormone management with either Lupron or Eligard was initiated at the start of chemotherapy. I remained on Lupron/Eligard for six years. After completion of 3 courses of chemotherapy, Casodex was administered daily in two doses, 10 mg and 20 mg for eight months.

After 12 years since the start of the trial, my metastatic lesions are resolved and my PSA is still undetectable. Two years after the cessation of hormone injections, I started 4 mg of Androgen to boost my Testosterone. My testosterone level is approx. 480. I have complete blood analyzed every four months.

Gourd Dancer

[Hidden in reply to Hidden]

Thanks for your very informative reply. My oncologist prescribed Keto because I am supposedly in the transition stage from CRPC to mCRPC. Before prescribing it, she had body scan done on me which showed no metastasis, which is good. So unless the body scan was not accurate, I am not ready for chemotherapy. Plus if it gets to that point, God forbid, I have a big decision to make. I am 77 years old and have lived long enough and prefer quality of life over longevity given a choice.

[Hidden in reply to Hidden]

Good for you. Before I had seeds implanted I had a bone scan and abdominal cramps scan. No mets. 12 months later two mets. Medical Oncologist told me that it did not matter which primary I had, it was too late. Then he explained micro metastasis caused by cancer cells floating around in the lymph and vascular systems look for a place to land and multiply

Hopefully you will not experience that scenario. At 58 I took a very aggressive posture in treatment of the Stage 4 Prostate Cancer. I also glad that I did and was able to find a remarkable researcher.

Keep kicking the bastard.

GD

[Hidden in reply to Hidden]

I was diagnosed with 24 PSA and Gleason 8 in May, 2002. Fortunately, I found proton beam therapy at Loma Linda for my primary and got there in November. Before going there, I was on preadjuvant hormone blockade therapy (Zoladex) on the advice of my urologist while I was searching for answers. Before Loma Linda started my treatment, they had an abdominal scan to rule out lymph involvement and fortunately I passed. But because of my high diagnosis stats, they gave me a triple part protocol of proton, photon and advice to go on hormonal blockade (Zoladex and Casodex) So I had that but instead of going continuously for 24 months, I elected intermittent androgen blockade (IAB) and that worked well for me until early this year. So counting from mid 2002 post diagnosis to today, I have so far beat the bastard for 14 years and still no signs of metastasis. I also read that the median lifetime of Keto before reaching mCRPC is 18 months. I hope to have that or even longer. I have a friend who took it for 7 years until he had to move on to Xtandi.

[Daddyishealing in reply to Hidden]

Gd. I'm not sure where you live but you seem to have an incredible doctor/researcher. Do you mind sharing that info?

[Hidden in reply to Daddyishealing]

I do have an incredible Doctor who has spent years in researching kidney and prostate cancer; Dr. Robert Amato. When I met him he was on the faculty of Baylor Medical School and practicing through Methodist Hospital. When Baylor divorced Methodist he rolled over to Cornell Medical School. And finally went back to the University of Texad Health Science Center and Herman Memorial Cancer Center, all in the Ztexas Meducal Center. He also was at MD Anderson Cancer Center and the University of Texas.

He was recommended by one of my Radiation Oncologist who was also in academia as someone that he would seek out if he was in my shoes.

GD

[GAdrummer]

My husband was on Lupron + ketoconazole + high dose prednizone. At the start his PSA was 10.1, after a month and a half it was 4.2, at two months 1.7, then stayed at 0.7 for six months before starting to shoot back up. One medicine does not work for all men with mPCA all the time.

[Hidden in reply to GAdrummer]

Thanks for your reply. I hope for the best for your husband. I just started Keto after 14 years post diagnosis, proton beam radiation and intermittent androgen blockade. I am not metastatic yet and hope will continue to hold off with Keto.

[GAdrummer in reply to Hidden]

It's a roller coaster journey we've been on for 7 years when he was diagnosed GS 9, PSA 40 with lymph node involvement between the kidneys and aorta that no one locally would touch with surgery or radiation. His doubling time after the Extandi failed was 2 months. We just tried VT-464 on a clinical trial and had to quit because the side effects got too serious: metabolic encephalopathy that hasn't disappeared after one month off the drug. All the drug did was stabilize the PSA at the level before starting it for 4 months.

[Hidden]

I never had or knew about Avodart until I joined this community a few weeks ago. But if it is a suggestion for the initial stages, I am past that already. I had successful Hormone suppression for 11 years following proton beam radiation. Early this year I reached castrate resistance so I was prescribed Ketoconazole. I hope I am just one of the 50% that need to wait it out. At least my PSA has stayed steady at the lower teens and not gone higher than the 17 when I started two months ago. Thanks for your feedback.

[Dan59]

I remember with keto it was important to take it with a acetic beverage , like coca cola to increase absorption

[Hidden in reply to Dan59]

Thanks. I do remember coming across that in my research. I have ginger ale and that should help

[Hidden]

I will do as you suggest. Although not necessary as I take your word, I might find additional details to share with my oncologist. Although she is not a specialist in prostate cancer, she treats me with respect unlike many, if not most, doctors who get defensive when they have a patient who knows so much, sometimes more than they. Ha! Ha!

[Dan59]

Yes I believe other than coke or pepsi I believe ginger ale to be the most acetic

[Hidden]

Interesting information, thank you. Ketoconazole works differently than anti-androgens like Lupron, Eligard, Zoladex, Casodex and the like. Keto lowers testosterone by blocking the action of androgen receptors. So it is prescribed when the anti-androgens stop working, which is what happened to me after 14 years on Zoladex and Casodex. I am hoping to solve my problems with Keto by following suggestions like taking it with acidic drinks like Coca Cola and ginger ale, which allegedly improve absorption. Even if I don't reach undetectable PSA as long as I can lower it to single figures. Better than having to move to chemotherapy which I am not qualified for yet because my recent scan showed no metastasis.

[Sisira]

Dear Fred,

Please find my response to your last writing to me a few days back which appears under Replies to my original post. It has nothing to do with "Ketokonazole".

Sisira

[Hidden in reply to Sisira]

Dear Sisira,

Thanks. I am glad I found this letter because I wanted to start a private conversation with you but I got lost and did not know where to look. Looks like I have to start with your original post and find my way to the spot where we left off a few days ago. But before I go there, I have another post on the subject of ketoconazole for everyone.

When I could not tolerate the side effects of keto (nausea, lack of appetite, fatigue, insomnia) I finally relented and asked my med onc for the steroid that she promised to prescribe should I need it. She gave me hydrocortisone 20 mg three times a day which I take after keto and a meal. I asked her why not prednisone. I did not tell her that my research showed that is what everyone else is taking. She said, "No, prednisone is not for PCa." So either she knows something others don't or she is misinformed. There was a little glitz. She wanted to be sure the prescription does not mess up a melangioma that an MRI showed in my brain. So she asked me to consult a neurologist or my family doctor. There was confusion in the communication and the pharmacy called me to say that it was ready. I won't make an issue out of it. I took it anyway and will take full responsibility. I now have a full appetite; it's great to finally enjoy my food. Any words of wisdom?

Fred Agnir

[Sisira in reply to Hidden]

Dear Fred,

I hope you are aware that my pathological condition is entirely different to that of yours and I have not used Ketoconazole in my treatment protocols. But I have some knowledge about these drugs which I would like to share with you and hope will help you to understand better the issue you have with your med onco.

Steroids such as Hydrocortisone, Prednisone, Dexamethasone and Triamcinolone ( new drug ) are all in the same category of synthetic drugs used in combination with strong cancer drugs such as Ketoconazole and chemo pharmaceuticals such as Docetaxel etc. in treating CRPC .Prednisone is invariably used in combination with Docetaxel and other chemo drugs and may be used with Ketoconazole as well. It is wrong to say Prednisone is not used in treating PCa as a combination drug.

Dr.Charles Snuffy Myres who is a reputed med onco specialising in treating PCa, often uses Ketoconazole in combination with Hydrocortisone when treating patients with CRPC. High doses of Ketoconazole like 400mg should never be used without the combination of a steroid.

Dr.Small, another popular med onco who is specialising in treating PCa, uses 200mg dose and says in many cases it is equally effective in treating PCa with Ketoconazole and there will be hardly any side effects. However, decision on the dose is up to your onco, depending on the severity of your case.

Ketoconazole has to be taken every 8 hours by the clock. It needs to be taken with an acid beverage like soda, pepsi, gingerale etc. and never with grape fruit juice. Ketoconazole interferes with the body's disposal of half of all prescription drugs including widely used antibiotics.

When Ketoconazole is used in high doses of 400mg three times daily, it is often associated with significant side effects such as nausea, vomiting, malaise and liver damage. Liver functions should be carefully monitored during this therapy.

The main action of Ketoconazole is the suppression of adrenal androgen production. But at the same time it impairs the adrenal production of steroids like cortisone.Steroids are important in maintaining the energy levels of the body, improve your appetite and relieve pain etc. Therefore steroidal drugs such as Hydrocortisone should be used in combination when Ketoconazole is used, to supplement the steroid loss.

By the way, you can use this site for private conversations as well without disturbing others. Follow the simple steps given below.

1. Click on the name of the intended person. That person's individual screen will come.

2. In this screen, right side top corner there is a box - "Message." Click on the "Message"

3. You will get another screen with a box to type your message. Once you complete your writing click on the "Send" button.

Your message will be received only by the intended person.

Now that you have my e-mail address too, you may use it if you feel it is more appropriate.

Good luck and God Bless you!

Sisira

[Hidden in reply to Sisira]

Dear Sisira,

Thank you for your letter which continues to demonstrate how caring you are and how much help you are able to give because of your wide knowledge. Just from your letter, I have learned so much that is vital to my fight against this disease. Some of what you advised are new to me and necessary and will surely make a difference in the outcome of my treatment. I think that what you say is of value to others in this community as well and that is why I am responding publicly. I will use a private conversation if and when I dwell on topics that have little to do with PCa.

I did start with 200 mg after pleading with my med onco. She was reluctant to give me permission to start low, saying that it was tantamount to a placebo. Eventually she convinced me to go to 400 mg, promising that should I be unable to tolerate the side effects, she would prescribe a steroid. When I reported suffering from nausea, fatigue and loss of appetite, she prescribed hydrocortisone, which puzzled me because all I hear about from others is prednisone. I now understand what she meant. She presumably knows that, as you say, prednisone is usually used in combination with chemo, which stage I am not at yet, thank God.

I did not know about the strict regimen of exactly eight hours between doses. Although it will take some effort, I will try to follow it. Ditto strictly monitoring my liver functions. I will be more diligent in taking liver detoxification measures.

Thank you as well for an earlier information on oligometastasis and the pioneering work of Mayo Clinic’s Dr. Kwon. I was completely blown away by his video presentation, which shows that oligometastasis can now be accurately identified and successfully eradicated. It made me wish it was available in 2006 when my PSA started to rise post primary treatment. At any rate, it is now too late for me to take advantage of it and probably would not be accepted into Dr. Kwon’s program given my age and disease stage. But I am sharing what you gave me to quite a few who come to me for advice, especially those who are in an earlier stage of recurrence.

I wish you well in your own PCa journey and for your admirable mission of helping others. There’s a special place in God’s future for you.

Always,

Fred

[Sisira in reply to Hidden]

Dear Fred,

Your words are very touching and encouraging.

I am glad to have learned that the information I passed on to you was useful to you.

Being diagnosed only in 2015, I am still in the beginning of my learning curve. But I feel confident, that I have gathered a substantial knowledge on Prostate Cancer within a very short time. I have built it up very methodically so that I can transfer what I have gained for the benefit of others who are in need which in turn gives me great pleasure to be of service to those who suffer along with me. Besides, I am from a small Asian country ( Sri Lanka ) with very limited hospital facilities!

As you have proposed it is always better to exchange our views on PCa publicly on this site for the benefit of all. On the other hand, since we are not qualified doctors, in case we have misconceived or misinterpreted something, a more knowledgeable person in the group can correct us. That will always enrich our learning process.

My ardent wish is to be a brave warrior in this battle and fight it for me and for others until we reach Victory together! In the background, throughout I hear your favourite and emotional song "I want to live."

Yes, life is to live but happily and meaningfully - may be short - may be long.

God Bless you my friend!

Sisira

[Hidden in reply to Sisira]

Here's a new twist in my protocol for which I would appreciate some feedback. I rushed to my family doctor yesterday because my foot is swollen. I had suspected it because of heaviness in the lower extremities but did not see the extent till I took off my shoes and saw the evidence. Naturally, it is disturbing because it could suggest a cardiovascular event. The doctor said it has to be the hydrocortisone, perhaps reasoning from the timing of my discovery. She told me to stop the hydrocortisone by tapering it off. When I asked her if it is OK then to try prednisone or some other, she said if if is hydrocortisone, the same thing would happen with any other steroid. It will take about a week for me to finish the tapering off and then we will find out if she is correct. I hate to stop it because it has improved everything from gaining my appetite to no more nausea and renewed energy. On the other hand, can the swelling be a side effect of the ketoconazole? Any thoughts?

[Sisira in reply to Hidden]

Both you and your doctor seem to have acted properly in the new situation you are facing. Yes as you have suspected swelling can be due to ketokonazole, hydrocortisone or in the extreme cardio vascular issue. Tapering the dose of hydrocortisone can be an effective strategy. Up to about 30% of patients using hydrocortisone are bound to be affected by the kind of swelling you are experiencing depending on the dose of the steroid and the period of use. Now let us analyse some information which may help you to manage the problem with better understanding and more confidence.

Swelling known as edema is a build up of fluid in the body. Swelling most often affects feet, anckles and hands. But swelling can also affect other parts of the body such as the abdomen and face.Causes of swelling include : heart disease, liver disease, aggressive treatments given for cancer and various drugs and allergic conditions. Yours is most likely due to the present treatment you are receiving. Dr. Charles Myres when using ketoconazole 400mg 3 times daily combines it with hydrocortisone at a dose of 20mg in the morning and 10mg in the evening. Through experience he must be knowing 30mg for a day could be tolerated by the majority of individulas without compromising too much on the benefits of the steroid that should be used to maintain loss of appetite, nausea, vomiting and the like side effects associated with strong cancer treatment drugs such as ketoconazole and chemo pharmaceuticals. The intended objective of your doctor to reduce the dosage of hydrocortisone to 30mg for a day in the tapering strategy could be beneficial. Sometimes, individuals react differently to different drugs in the same class. Therefore, experimenting with different steroids without aggravating the conditions can be meaningful. Prostate cancer is heterogeneous and is a genetic malfunction that individual responses and tolerance to the same drug can be different.

Now the things you can do to ameliorate your troublesome condition are the following :

- Elevate your feet as often as possible ( Either sitting in a chair with your feet on a stool with a pillow or in the bed or couch with feet up on two pillows )

- Do not stand for a long period of time.

- Avoid tight shoes.

- Do not cross your legs.

- Reduce your salt intake.

- Eat balanced diet.

Depending on the causes of your swelling your doctor may adjust your medication and/or prescribe suitable medicine - Eg. Diuretics - may be known as "water pills" as they would be making you urinate out extra fluid.

Hope you may be able to use this information when you discuss your fluid retention ( swelling - edema ) issue with your med onco.

Best regards and God Bless you.

[Sisira in reply to Sisira]

Above reply is from me, your good friend Sisira. I forgot to type my name below the text.

Cheers.

[Hidden in reply to Sisira]

No problem, Sisia. The message could not have come from anybody else but you from the content and I have no other private conversations with anybody else.

Thanks for all the information. The doctor I am working with right now is my family doctor. But she and my med onco are coordinating on this treatment. I have the most beautiful relationship with both and am very lucky.

I did ask her last time if she would prescribe me a diuretic and she said she will after we get to the 30 mg a day dose and I still have swelling. I am finishing the 40 mg dose tomorrow so I start the 30 mg dose on Monday. A week after, she will see me and then we will evaluate and take it to the next step. The day after that, I see my med onco. She will be very pleased at how my family doctor and I worked together.

I have frequent blood tests and am pleased that liver functions are normal. I have also become more studious in taking my liver detox supplement. I have also started taking a supplement called Vital Reds. It promises to boost metabolism. It seems to have arrested the precipitous downward slide of my weight. It seemed that no matter how much I was eating, I kept losing weight. So boosting my metabolism might work. Vital Reds has a lot of vitamins so I have substituted it for my multivamins supplement.

Thanks for the advice on keeping my feet up and avoiding long standing. As for diet, you and I know as Asians how much of a challenge it is. And I love those potato chips.

Blessings,

Fred