randomized to interferon in clinical trial

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12/16/2013 3:41pm
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hello friends.   this is my first post, though i have been lurking for the past 3 months or so.  july 12,2012 i had a melanoma, 3.05   without an irritated site.  removed along with an alledged negative snb.  one small area of which had an area that the pathologist would not declare negative, nor would he declare it positive.     i thought i was in good shape.  had a good year.   august 2013, noted groin  node in lymph area of past surgical site.  (left ankle)   had node removed and clean out of lymph nodes.   wore drain 4 weeks, then had 23 days or radiation to site.   was waiting for randomization to trial   of 2 arms  ipi and l arm interferon.      just learned that i was placed in the interferon group.        i am a robust 75 who looks 65 and is healty other than a little arthritis and hypertension.and don't want to waste one of my possible last years being miserable          i did learn through probling my onc, (very nice, but not mel specialist) that i am braf negative, and NRAS positive.  (i know this is not good news)   i have just completed negative pet and ct scan or head. ( i cannot have mri or head due to implant in ear)    i am asking for advice re next step.   i would like to see a mel specialist at a large cancer center.   vanderbilt is much more convenient, sloan kettering could be managed.   and what is "watch and wait" really like.   is that good enough for me.    any bit of info provided would be appreciated and evaluated.   i have learned so much from this site and felt such kindess and knowledge frin every post.     thanks to you all.     

I've been reading up about interferon. I'm beginning to understand why there is so much confusion and controversy about it. Part of the problem, especially in the early clinical trials intended to gain FDA approval for interferon, is that neither sentinal node biopsy nor complete lymphadenectomy were commonly practiced at the time. Lymph node involvement is an important progostic indicator for melanoma and that was not always determined in these studies. 

The second problem I see is that many of the treatment guidelines published prior to 2011 (when Zelboraf was approved) or 2012 (when Yervoy was approved) had nothing to offer patients that was better than interferon. Once someone became Stage IV it was going to be "lights out" for them in 6 to 9 months so you might as well take interferon and hope for the best. 

The best write-up I have seen about interferon for Stage III patients at high risk for recurrence (i.e., primary lesion >4.0mm or any lesion with lymph node involvement) is from Canada (published in 2009 and updated in 2013). "Systemic Adjuvant Therapy for Patients at High Risk for Recurrent Melanoma".

Basically, they recommend that Stage III patients at high risk for recurrence find a clinical trial because "at most a small overall survival benefit exits" for interferon with or without chemotherapy. If one is going to do interferon, the only significant benefit results from doing the whole year-- 1 month of high dose interferon followed by 11 months of low dose interferon.  

One of the major interferon clinical trials (from 2000) said that 44% of high dose interferon patients remained disease free for 5 years while 35% of the control arm (observation only) remained disease free for 5 years. That is a net benefit to 9% of the patients. They also said that there was no difference in overall survival between the interferon arms and the observation arm. In other words, interferon may delay recurrence of melanoma in 9% of the people who take it. But once it recurs, the prognosis is bleak (remember, that was back in 2000 when no other treatments were available).

As always, the choice of treatment is a very individual and personal decision. A lot of factors have to be taken into account including whether or not you have young children to care for and how many years you expect to live during which the melanoma could reccur-- melanoma at 30 is different from melanoma at 70. But personally, I would not be too afraid of Stage III melanoma. Stage III is not going to kill you. If and when you get to Stage IV, there are several treatment options available to you that are not currently available to Stage III patients and more treatments are in the pipeline.

If it was me--at my age (semi-retired) and with no children, I would pass on the interferon. I would try to find a promising clinical trial. If no trials were available, I would watch and wait and enjoy my life to the max unless and unitl  I hit Stage IV.

POW,

This is a great document that you posted. I actually used this as a part of my decision making process on whether or not to do Adjuvant Interferon Therapy. From all the reading ive done, it seems like time after time the conclusion is that it is very controversial. Again a very personal decision but you must be confident in your choice and never look back.

Samuel

Lucy,

A couple years ago I was stage III and got randomized into the interferon arm of the same trial.  I did the full year of interferon and even though I managed fairly well compared to others it still was no picnic.  About 4 months after finishing my year I progressed to stage IV.  POW's summary is right on the money.  I knew the long term survival was not helped much by interferon but I felt there was enough evidence it might delay a recurrance to give it a try.  I was 43 at the time with a 1 year old and 3 year old.  Would I do it again?  Yes.  Would I do it if I was 75?  Probably not.  You have about a 50-50 chance of having a recurrance.  If it were me I would start looking at getting myself as healthy as I could with exercise, nutrition, and supplements (despite the recent thread on supplements I think it's worth a try).  I would look for other clinical trials if they are available.  Finding clinical trials in the adjuvant setting is tricky but there have been various vaccine trials in the past.

Good luck Lucy.  Sorry you are in your situation but try your best to stay positive.  The recent advances in treatment options for stage IV has been amazing the last couple years.  Hopefully you won't ever need them but it's nice to know that if you do some of them should be availble in the not too distant future.

Brian

Thanks to you and the others who so graciously answered my post.  I see my  understanding onc tomorrow for her input re another  trial and a referral to a larger treatment center.   And my thoughts of  gratitude and support for all  of you.  Lucy 3

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241890/

Basically says 47% of NRAS patients responded to IL-2

2013 NIH report NRAS & IL-2

Should read the full report.

 

The purpose of this study is to identify clinical and molecular characteristics of melanoma patients that predict response to high-dose interleukin-2 (HD IL-2) in order to improve patient selection for this approved but toxic therapy.

We reviewed the records of 208 patients with unresectable stage III/IV melanoma treated with HD IL-2 at The University of Texas M.D Anderson Cancer Center (MDACC) (n=100) and Beth Israel Deaconess Medical Center (BIDMC) (n=108) between 2003 and 2009. The BRAF and NRAS mutation status of the tumors was determined for patients with available tissue samples and the mutation status and clinical characteristics were compared to clinical outcomes. Pre-treatment serum lactate dehydrogenase (LDH) levels were available for most patients (n=194). Tissue was available for mutational analysis on a subset of patients (n=103) and the prevalence of mutations was as follows: BRAF 60%, NRAS 15%, WT/WT 25%. In the subset of patients for which mutational analysis was available, there was a significant difference in the response rate based on the mutation status: NRAS 47%, BRAF 23%, and WT/WT 12% (p=0.05). Patients with NRAS mutations had non-statistically longer overall survival (5.3 versus 2.4 years, p=0.30) and progression free survival (214 versus 70 days, p=0.13). Patients with an elevated LDH had a decreased PFS (46 versus 76 days, p<0.0001), decreased OS (0.56 versus 1.97 years, p<0.0001), and trended toward a decreased response rate (7% versus 21%, p=0.08). NRAS mutational status is a new candidate biomarkers for selecting patients with melanoma for HD IL-2 treatment.

 

I'm me, not a statistic. Praying to not be one for years yet.

Great information Jerry.  Thanks.

Uggh. Not anonymous. Kylez.

Thank you to everyone able to post non-anonymously, it helps add to the sense of community!

Anonymous - (1/3/2014 - 11:08pm)

Thansk Jerry. I wonder how many of us have even been tested for NRAS? I am seen at an academic institution and they sequenced my tumor a couple of years ago and found an NRAS G12A mutation. There's a few NRAS mutations noted for melanoma, that's one of them.

I also responded to HD IL-2 in my lungs bilaterally, both were NED on the PET scan after 2 cycles IIRC. That hasn't been the end of the story for me but it was a very good start. I haven't hit 5.3 years yet but I like those numbers. They would seem to be a (very) good reason to keep HD IL2 around as a tx.

 

^^^^ kylez.

Thank you to everyone able to post non-anonymously, it helps add to the sense of community!