What is the most successful drug against cancer ?

It is Avastin (bevacizumab).
A slide-presentation about Zytiga (by Janssen Biotech/Johnson & Johnson), which I saw on the internet, contained a slide with a graph that had on the vertical axis the 'billions of dollars accumulated since the introduction of a drug' versus the date (up to 2013) horizontally. A successful drug does not only rise fast, but keeps rising. This requires a high price and an increasing number of patients using it. And Avastin was said to be the most successful drug.

From Wikipedia: Bevacizumab (trade name Avastin, by Genentech/Roche) is an angiogenesis inhibitor, a drug that slows the growth of new blood vessels, required for tumor growth. It is licensed to treat various cancers, including colorectal, lung, breast (outside the USA; in USA approved in 2008, approval withdrawn in 2011), glioblastoma (USA only), kidney and ovarian. First approval was in 2004... Clinical trials are underway for many other indications... Typical cost of Avastin: $50,000 a year.

Already in 1998 'dr. Bob' Leibowitz started treating PCa patients with thalidomide (Thalomid/Celgene Corp) as an anti-angiogenic agent. The USA-FDA granted approval of thalidomide in 2006 for multiple myeloma (a cancer of the blood), 7 years after its efficacy had already been confirmed in the medical literature. And Celgene took advantage of "off-label" marketing opportunities to promote the drug in advance of its FDA approval for the myeloma indication (Wikipedia).

Lenalidomide (Revlimid/Celgene) is a derivative of thalidomide introduced in 2004. On June 29, 2006, lenalidomide received USA-FDA clearance for use in combination with dexamethasone in patients with multiple myeloma. It is undergoing clinical trial as a treatment for Hodgkin's Lymphoma, as well as non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia and solid tumor cancers, such as carcinoma of the pancreas. It costs $163,381 per year for the average patient (Wikipedia).

Drugs like Avastin, Thalomid, Revlimid, that slow the growth of tumors: no cancer patient should be without it. So where do we, metastatic PCa patients stand, what do we have ? None, nothing. Yes, when you go to the private clinic of 'dr. Bob' , you will get all 3 of them, "off-label" , so not paid for by your insurance. And they are very expensive.

When the price of drugs are increasing the way they are currently doing, there comes a point where our society will be not willing to pay for it. This happened in the UK where Zytiga(abiraterone) was considered too expensive for use on the National Health Service(NHS).
"There is no set threshold cost per QALY (quality-adjusted life year) of drugs that meet the end of life criteria, but since the supplementary advice was introduced, the highest cost per QALY of a recommended drug has been £50,000 (for renal cell carcinoma). Therefore the £63,200 cost per QALY for abiraterone would still not be deemed a cost effective use of NHS resources," said a Nice statement. Nice is the National Institute for Health and Clinical Excellence in the UK.

Abiraterone was developed by scientists at the Institute of Cancer Research (ICR) and the Royal Marsden in London. When I had been a UK-taxpayer (I am not) then I would think I should get it for free, because I had already paid for all this academic research.

Avastin was used in a clinical trial for prostate cancer several years ago and failed miserably. A good friend of mine was in it.
http://www.nytimes.com/2010/03/13/business/13drug.html?_r=0

Angiogenisis inhibitors are not all alike and act in different ways. Tasquinimod is the hot new one for prostate cancer and seems to be doing well so far in clinical trials. It is in Phase III now. Lenalinomide is in tests as well. There is new one called AMG 386 that is being tested with abiraterone now.

There has been some research that suggests that some angiogenesis inhibitors may only be beneficial at very low doses, but may interfere with chemo at higher doses. High doses may create an immunosuppressive response that paradoxically encourages tumor growth. Low doses are being tested in clinical trials.

- Allen

Many PC patients lack VEGF marker on the PC cells that Avastin binds to. Ideally, patients should be screened for VEGF marker, and if positive, it could be assumed that Avastin would help their particular case.

Special Lady, that’s the point: Diagnostics first, then comes the appropriate therapy! BTW: Thalidomide is more of an immunomodulator or stimulator than an VEGF Blocker, and that might be beneficial! Thalidomide suppresses the TNF- α production, reduce the expression of proangiogenic factors, such as VEGF and IL-6 and induces NK cells!

Fairwind said...
Outside the U.S. most cancer victims just get sick and die, the lifesaving drugs are simply not available to them..

So "outside the US most cancer victims just get sick and die".
I wonder if Americans realize just how offensive is this unmitigated drivel. Good manners prevents me from posting a link to a very recent news article ----------- nah, bugger good manners ---- here it is.


www.news.com.au/lifestyle/health-fitness/australian-cancer-patients-have-highest-survival-rate-in-world/story-fneuzlbd-1226593471571

And, I should think that remarkably similar cure rates apply in most developed countries.

Post Edited (BillyMac) : 3/12/2013 3:10:41 AM (GMT-6)

So far, Avastin seems to be working well for me (click on my PCa History, below). Currently, PSA = 0.2 one year after the end of medication. I stay on the trial 'til my PSA reaches 2.0. Now, I understand that these results could be solely due to the ADT2, but that's what the trial is for. I really interested to see how the control group fared. btw, this trial is for Avastin much earlier in Prostate cancer progression than the trial that did not meet end-point.

...Jerry

Tall Allen said...
Avastin was used in a clinical trial for prostate cancer several years ago and failed miserably. A good friend of mine was in it.
www.nytimes.com/2010/03/13/business/13drug.html?_r=0

- Allen

Failed miserably ? Addition of Avastin increased the median Overall Survival from 21.5 to 22.6 months, the median Progression Free Survival from 7.5 to 9.9 months, and the Objective Response from 35.5 to 49.4%.
Although, Grade 3 or greater treatment-related toxicity increased as well, from 56.2 to 75.4%.
Because OS is the main objective (it should not be !) the extra 1.1 months is considered too little.

Synergy in combinations should be used in the first place to lower doses and therefore lower SEs.

What I consider a miserable failure is MAILSAIL. When some patients can barely stand 5 mg Revlimid then 25 mg for 14 days is a terrible mistake. This shows in the reported dose-reductions and high toxicity. It should have been 5 mg for 21 days in the 3-weekly cycle. And synergy should imply a sizeable reduction of the doses of docetaxel as well. Hopefully to the point that the toxicity of the combination becomes lower than that of docetaxel alone. By the way: I was asked to join MAILSAIL in sept'2010. Glad I didn't.

On the AUA 2012 dr. Oliver Sartor said: "It takes 4 drugs to cure Hodgkin's disease - clearly multiple drugs will be necessary to take the next big step." And in one of his videos dr. Charles Meyers talked about combinations the same way. askdrmyers.wordpress.com/page/3/ Combining PCa Drugs, Posted October 17, 2012.

Post Edited (Arno) : 3/13/2013 10:00:49 AM (GMT-6)

Tall Allen said...
Here's the ASCO Presentation:
meeting.ascopubs.org/cgi/content/abstract/28/18_suppl/LBA4511

Avastin (added to docetaxel/prednisone) treatment-related deaths were 4-fold higher than docetaxel/prednisone alone. Grade 3 or higher AEs increased by 35% and included fatigue, febrile neutropenia, hypertension, and gastrointestinal perforation and hemorrhage. There was no statistically significant increase in overall survival.

- Allen

Statistics ! On 1050 patients in the trial 1 patient died in one branch, 4 in the other one. Yes, 4-fold higher, but how many can you expect beforehand ? And the 35% increase of serious SEs: it looks quite different when you look at the actual numbers, 56.2 vs. 75.4%, so an increase of 34%. But it shows that docetaxel by itself already has much too much serious SEs.

The problem with these trials is that the desingers take the original treatment and add, more or less in isolation, the other drug. Anxious to get a significant difference it is taken at a too high dose.
There is no attempt to find a combination that improves on response and on SEs. In the MAILSAIL trial this was so bad that they had to stop early because of the high toxicity.

Sorry, Allen, I had not looked at the 'treatement-related' deaths (might be somewhat difficult to decide if it is PCa-related, or so-called co-morbidity, or treatment-related).

But, even with the extra 'treatment-related' deaths, there was still a survival benefit, meaning that the the time it took that 50% of the patients were dead, was 22.6 months vs. 21.5 months. A 1.1 months benefit, which, when no accuracies of the underlying numbers are given, might or might not be significantly different from zero.

Post Edited (Arno) : 3/13/2013 2:58:32 PM (GMT-6)

Moreover, Overall Survival (OS), I prefer to think of it as Time To Death (TTD), is not so relevant anymore for docetaxel. When it failed there are several other drugs, such as cabazitaxel (Jevtana), abiraterone (Zytiga) and others, so there is no reason to wait until you are dead after docetaxel failed.
Then it is much more important that you experienced a better Progression Free Survival time and a better reduction of the tumor (both PSA and alkaline phosphatase).