Not yet a member?

    Popular Topics
    Search


    Forums
  • Forums
  • Ask a question about:

  • Archived Onctalk Forums
    Our Supporters
    Syndication
    Subscribe

High Blood Pressure and Anti-Angiogenic Therapy: A Beneficial Side Effect?

October 20, 2009 - 9:59 pm     Print This Post Print This Post     view / write comments

1 Star2 Stars3 Stars4 Stars5 Stars (2 votes, average: 5.00 out of 5)
Loading ... Loading ...
 Dr West

One of the most common side effects of many different anti-angiogenic agents, which are felt to decrease the tumor’s blood supply, is high blood pressure, also known as hypertension.   The cause of this isn’t really known, but most patients develop some degree of high blood pressure.  What is interesting is that there is growing evidence that this may not just be an unwanted side effect, but rather a marker of a probability of doing better, similar to the correlation of rash with longer survival in patients receiving EGFR inhibitors.

For this, we can start by looking at results from a recent study of the anti-angiogenic agent sorafenib (nexavar) in renal cell carcinoma (kidney cancer).  Here, patients were classified according to whether they demonstrated evidence of a high blood pressure, which was defined as a systolic blood pressure (the higher number) of 140 or greater, and/or a diastolic blood pressure (the lower number) of 90 or greater over the course of their treatment with sorafenib. The 441 of 534 (83%) who had hypertension had a remarkably higher response rate (54% vs. 10%, p < 0.0001), and a significantly longer median progression-free survival (12.5 vs. 2.5 months, p < 0.0001) and median overall survival (30.5 vs. 7.8 months, p < 0.0001) than the patients with advanced RCC who didn’t have hypertension on the study:

motzer-rcc-and-htn

Interestingly, and importantly, the study showed that it didn’t seem to matter much whether patients were treated with a dose reduction of sorafenib, started anti-hypertensive (blood pressure) medicines, or both; the only people who seemed to do poorly were those who never developed high pressure.

htn-dose-reductions-and-anti-htn-medications

Perhaps that’s a fluke, but the same trend has been seen in lung cancer, although without as striking a difference.  In a retrospective analysis from the ECOG 4599 trial of carbo/taxol alone or combined with avastin (bevacizumab), patients with high blood pressure on avastin (in this case defined by a much higher bar of a BP above 150 systolic and 100 diastolic) had a median progression-free survivalof 8.0 vs. 4.5 months for those with hypertensive events, while the median overall survival was 14 months, vs. 11.3 months (neither statistically significant).  And in a review of a global registry of over 2000 patients receiving avastin in advanced lung cancer that was presented by Dr. Nick Thatcher at the World Conference on Lung Cancer in San Francisco earlier this year (abstract not available), the median overall survival was 18.8 months for those with hypertension, compared with 12. 9 months for those who didn’t show significantly elevated blood pressure.

These are still early reports and represent a small minority of the work being done with anti-angiogenic agents in cancer.  Nevertheless, it’s intriguing to see the same trends applying to patients being treated with different anti-angiogenic agents for different cancers, and in several different studies.  This issue certainly merits further study and raises the question of whether modifying the dose of anti-angiogenic agents in an attempt to develop high blood pressure, possibly as a biomarker that the drug is acting as intended, may possibly be beneficial.  This is not the standard approach right now, but we should see more information about the association of blood pressure and survival with various anti-angiogenic agents in oncology in the coming years.

No related posts.

Related posts brought to you by Yet Another Related Posts Plugin.

Posted in: Anti-angiogenic agents, Cancer Treatments, Pain and Symptom Management, Treatment Print This Post Print This Post


  1. October 22, 2009 - 4:36 pm

    My adjuvant treatment mimicked ECOG 1505, featuring maintenance avastin. At about month 7-8 (with NED), I began having problems with hypertension. Also developed proteinuria, but within tolerable limits. BP was deemed too high (~150/100), however, so I began taking Atavan which was effective in reducing the BP. However, my cancer recurrence followed right afterwards at about month 10-11. Coincidence? I have continued the BP medicine even though I have moved on to Tarceva, largely because I am not in the shape I used to be in before all this happened and I was happily training for a marathon. I wonder if I should stop the BP meds at this point.

    road runner
  2. October 22, 2009 - 5:08 pm

    I would caution that the second figure in the post shows that people with renal cell carcinoma who had BP controlled did comparably if they started BP meds or had a dose reduction for hypertension. The only arm that clearly did worse is the arm that didn’t develop any hypertension at all.

    -Dr. West

    Dr West
  3. October 27, 2009 - 5:00 pm

    Thank you Dr. West for news of this study. I received Tarceva for a year as part of a trial looking for possible chemopreventative properties. Several months into the trial it was decided that I should be sent to an Internist because I had elevated blood pressure on each follow up visit.

    As I use to keep close check on my BP prior to the discovery of my cancer, I could not help but wonder if the reason I was now experiencing hypertension had anything at all to do with my treatment program (docetaxol & cisplatin)or the Tarceva.

    I was told that because I am , “a minority, overweight, and middle-aged (44)” that these had to be the reasons why I was now hypertensive. I never believed that was so as I was all of those things before my cancer was discovered and was not hypertensive.

    My question for you though is about any data regarding a drop of BP back to previous levels? I began taking hypertension medicines about 5 moths into the trial, and I haven’t been able to return to normal BP despite losing 40lbs and exercising 5-6 days a week, and reducing my salt intake. I guess I am hoping that there is some clue that may help get me off of these meds (I now on 3), or reduce the number that I have to take?

    Thanks,
    Tex

    texatl
  4. October 27, 2009 - 7:22 pm

    Sorry, not yet. Oncologists aren’t used to focusing on blood pressure, except when it’s too low, and we’re only starting to sift through the data and get a sense that something’s going on here. Plenty of other questions follow from these early observations, but few if any answers yet.

    Dr West
  5. October 30, 2009 - 7:13 pm

    Ok, thanks again Dr. West.

    texatl
  6. January 21, 2010 - 12:59 pm

    Dr. West,

    Can you clarify whether the pts analyzed in these hypertension studies if any of them were previously already on HTN meds? I am wondering if someone is already on one or more HTN med(s) before starting Avastin how that affects this correlation.

    Thanks!

    rlei
  7. March 1, 2010 - 1:30 pm

    I am going through articles I missed and came across this one four months after it came out. I took Avastin for NSCLC for two periods with a break in between. All together about 15 months. The rise in blood pressure (140/90 at peak between treatments, 100-110/60 before treatments) was upsetting to me. I had learned to associate moderate numbers with good health and athletic activity. The whole blood pressure issue confused me. What was much more clear was that I did not like taking Avastin. Unlike standard chemotherapies, Avastin made me permanently lethargic. The first few months would be OK, and then things got tough. In response to my complaints, my doctor allowed me to reduce the frequency of dosing, but with each treatment cycle I became less tolerant of the treatment. When I skipped a treatment I felt like I was on vacation, my energy completely returned. It is hard to express the frustration and fear I felt during this time when my cancer was under control but I could not live an active life. My own ignorance of what was going on did not help matters. Perhaps with a better understanding of the physiology relating to this drug, I could have gotten more benefit from it.

    dfourer