Thursday, February 2, 2017

For Stage II/III melanoma patients: Interferon NO BETTER than observation!!!!

Since 2010, the beginning of this blog, I have been YELLING that interferon provides little to no help in stopping the progression of melanoma and NO effect on overall survival at all!!! (That's from the real live DATA people!)  It WILL, however, make you extremely ill! The problem has always been the presence of anecdotal "evidence" and the desire of folks to believe.  We've all heard this story, "Well, I'm Stage III and I took interferon and MY melanoma hasn't recurred!"  In melanoma world, when ANYONE fails to recur, that is WONDERFUL news!!!  However, these stories were never proof that interferon had ANYTHING to do with failure to progress.  Research has been lacking because, with no effective drugs for use as adjuvant, no one was really paying attention, AND - many folks with Stage II/III melanoma never progress even with no treatment!!!  Now there's this.....

Phase III Randomized Study of 4 Weeks of High-Dose Interferon-α-2b in Stage T2bNO, T3a-bNO, T4a-bNO, and T1-4N1a-2a (microscopic) Melanoma: A Trial of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group (E1697). Agarwala, Lee...Sosman, Flaherty, Sondak, ….Kirkwood. J Clin Oncol. 2017 Jan 30.

Purpose: To test the efficacy of 4 weeks of intravenous (IV) induction with high-dose interferon (IFN) as part of the Eastern Cooperative Oncology Group regimen compared with observation (OBS) in patients with surgically resected intermediate-risk melanoma.

Patients and Methods: In this intergroup international trial, eligible patients had surgically resected cutaneous melanoma in the following categories: (1) T2bN0, (2) T3a-bN0, (3) T4a-bN0, and (4) T1-4N1a-2a (microscopic). Patients were randomly assigned to receive IFN α-2b at 20 MU/m2/d IV for 5 days (Monday to Friday) every week for 4 weeks (IFN) or OBS. Stratification factors were pathologic lymph node status, lymph node staging procedure, Breslow depth, ulceration of the primary lesion, and disease stage. The primary end point was relapse-free survival. Secondary end points included overall survival, toxicity, and quality of life.

Results: A total of 1,150 patients were randomly assigned. At a median follow-up of 7 years, the 5-year relapse-free survival rate was 0.70 for OBS and 0.70 for IFN. The 5-year overall survival rate was 0.83 for OBS and 0.83 for IFN. Treatment-related grade 3 and higher toxicity was 4.6% versus 57.9% for OBS and IFN, respectively. Quality of life was worse for the treated group.

Conclusion: Four weeks of IV induction as part of the Eastern Cooperative Oncology Group high-dose IFN regimen is not better than OBS alone for patients with intermediate-risk melanoma as defined in this trial.

The results speak loud and clear!  Interferon is no better than observation alone!!!! However, there will certainly be those who say, "Yeah, well.  These folks only took it for 4 weeks. I took it for a year!!"  The facts remain:  All previous studies of interferon in melanoma (even when administered for a full year) have shown no change in overall survival for anyone and only in patients with ulcerated lesions was there the slightest benefit in progression free survival.  HOWEVER, now that ipi and anti-PD-1 are available, with far better outcomes than any ever delivered with interferon, I see NO REASON for anyone in need of adjuvant melanoma treatment to be relegated to this inhumane option.  Agarwala, Sondak, Flaherty and the King of all things interferon: Kirkwood ~ PLEASE!  Read and comprehend your own data!!! Work toward making anti-PD-1 available for your early Stage melanoma patients who desire treatment, rather than continuing to beat this dead horse!

Ok. Rant over.  I guess. - c


  1. Ugh. You have been telling everyone this FOREVER! I wish they would quit torturing patients with this stuff, while simultaneously letting their melanoma run rampant.

  2. Hi there...I've been reading your blog over the past few weeks, as I have melanoma, stage 3b. I'm impressed by your knowledge and spirit. In my case, after undergoing axilla lymph node dissection to take place next week (already had local dissection and sentinel node removal), the only adjuvant therapy I'm being offered (I'm in Nova Scotia, Canada) is IFN (1 month high dose and 11 months, 3 times/wk). I've been leaning towards doing it based on the following meta-analysis which seems to imply both RFS and OS are improved with IFN (see the plain language summary on page 2.

    Mocellin, S., Lens, M. B., Pasquali, S., Pilati, P., & Chiarion Sileni, V. (2013). Interferon alpha for the adjuvant treatment of cutaneous melanoma. The Cochrane Library.

    I'm trying to decide what to do. In your opinion would it be better to forget the IFN and wait for my cancer to get to stage IV at which point, I would be offered ipi, at least. Ipi is what is offered in NS for stage IV melanoma. Nivolumab (anti-PD-1) is not yet approved by Health Canada (our equivalent of the FDA).

    I understand if you are uncomfortable making any suggestion for me. Also, I have to admit that my oncologist is not encouraging me to take the IFN. While he admits it might improve RFS, he doesn't believe it improves OS which I'm suggesting to him is contradicted by this meta-analysis, I'm citing. He also believes not taking the IFN will provide me with a better quality of life (I'm 65 and very healthy, other than this cancer). :-)

    1. Note the date of the study you are reading. 2013. The one I posted above is from THIS YEAR!!! Additionally, the study I posted was written by some of those who have promoted IFN the longest, even in this day of new treatments for melanoma...Flaherty, Kirkwood and Sondak. With THIS data...even THEY had to say IFN did no better than observation for folks in your shoes. I can tell you no more than what I said in the post above... But...there is this: I was first diagnosed as 3b in 2003. There was NO ipi, anti-PD1 or BRAF inhibitors on the horizon for my use at that moment...or even if I progressed. They did not exist! And I still did not take IFN.

      I wish you luck with your decision. les

    2. PS I had a lovely visit to Nova Scotia a couple of years ago. Halifax is a great city, a fabulous place to hike inland and on the shore. I enjoyed amazing farmer's markets. Hallifax Gardern and the dahlias! Learned all about the explosion that took out large parts of the town and its inhabitants due to stubborn men steering boats loaded with dynamite! Oh my goodness! You are lucky to live in such a beautiful place. Hang in there. les

    3. Thanks so much for responding to my post, Les! I grew up in Halifax and now I live in a more rural area, east of Halifax. But my surgery will be in the city. Yes, I know that the meta-analysis was done in 2013 but it was reviewed again in 2015 and they felt that there were no new studies to contradict what they had determined in 2013. Of course that doesn't included anything published in 2016-2017. But being a meta-analysis, it looked at 17 trials with over 10,499 participants, so it was very comprehensive. But I'm going to take a closer look at this latest one you are citing and read all of your posts over the past 7 years. I'm sure it will help me decide what to do. One more question, if you don't mind - what is your theory for why oncologists would continue to recommend IFN if there is no efficacy for it?

  3. Money! More docs are invested in things (both egotistically and financially) than you may realize. And...some doctors have a real hard time telling folks they have no way to treat or prevent the disease process they are facing. It is very hard for patients to accept that as well. Currently NONE of the reputable Big Dogs in melanoma research are continuing to support the use of IFN in your circumstance. Some of them ARE looking at it for advanced folks in combination with other meds. But...those studies are either barely started or are just in planning phases. IFN is incredibly toxic so very few patients who wish to use it can tolerate the entire dosing schedule when using it alone. It remains to be seen if it will actually improve outcomes or be tolerable for folks at Stage IV. Hang in there. Melanoma is not easy.