MPIP: Melanoma Patients Information Page

The MPIP is the oldest and largest community of people affected by melanoma hosted through the Melanoma Research Foundation. It is designed to provide support and information to caregivers, patients, family and friends. Once you have been touched by melanoma—either as a patient or as a family member or friend of a patient—you become part of a community. It is not a community anyone joins willingly. But if you must be part of this group, you will find no better place to find the tools you need in your journey with this cancer, and the friends who can make that journey more bearable.

The information on the bulletin board is open and accessible to everyone. To add a new topic or to post a reply, you must be a registered user. Please note that you will be able to post both topics and replies anonymously even though you are logged in. All posts must abide by MRF posting policies.

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Patina's picture
Replies 8
Last reply 12/31/2013 - 2:06am

Hi,

Does anyone here know or have they experinced a reduction in visible tumors within weeks of taking Yervoy?  I can't find anything on this and wonder if anyone knows how good a sign this might be or not...

My Mother was diagnosed with stage IV and later brain mets.  She had gamma knife radiation for lesions on her brain and 4 days later had her first infusion of Yervoy. 

She had a very large tumor on her neck and 18 small to large tumors on her scalp.  There were 8 small lesions on her brain.

Two weeks later the tumor on her neck has shrunk by 50% and the tumors on her head are now hard compared to what they had been.  She still have 3 more treatments of Yervoy and I'm wondering how positive this might be or not...  

She goes in 3 weeks to get a MRI of her brain and we might know what is happening with her scalp, but its encouraging that the tumor on her neck is much smaller.

 

 

 

 

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JerryfromFauq's picture
Replies 10
Last reply 1/1/2014 - 3:56am
Replies by: JerryfromFauq, Joannezaras, POW, Anonymous, JoshF

Tried to post the URL so that you could read the whole long article.  Here's the start.    This is in response to the Gal that has been telling people that one must kill their immunsystem before they can receive IL-2. 

2013 IL-2 & T-Regs   Does IL-2 require killinig Immune system (Which includes our T-cells)?
Introduction

High-dose (HD) bolus IL-2 therapy is currently one of the most potent forms of immunotherapy and was approved by the FDA as a single-agent cytokine therapy for metastatic melanoma and renal cell carcinoma (1–3). Typical HD IL-2 therapy consists of bolus infusions of 600,000 or 720,000 IU/kg of aldesleukin (Novartis), and each cycle of therapy is aimed at giving up to 15 bolus infusions every 8 hours or as many as the patient can withstand due to toxicity (1, 4). The therapy cycle is then repeated approximately every 14 to 21 days for up to 6 to 8 cycles, depending on the clinical performance of each patient and toxicities associated with IL-2 therapy. Early single and multicenter clinical trials have consistently shown a 15%–16% partial and complete response rate in patients with stage IIIC or stage IV noncutaneous metastatic melanoma and in patients with renal cell carcinoma, among whom a smaller fraction of patients (about 5%) experience durable long-lasting complete remission for years (1, 2, 5). HD IL-2 has also been combined with other immunotherapies, including adoptive T cell therapy using ex vivo–expanded tumor-infiltrating lymphocytes (6–8) and tumor antigen peptide vaccines (9), where it may enhance antitumor T cell function. IL-2 is known to induce NK cell and CD8+ T cell proliferation, survival, and acquisition of effector function through STAT5 activation (10–12). Increased tumor-infiltrating and circulating perforin+ (PRF1+) NK cells and activated CD8+ T cells have been found in most patients undergoing HD IL-2 therapy, but this finding did not always correlate with tumor regression or clinical response (13–15).

One of the key problems with HD IL-2 therapy, which limits its more widespread use, is its adverse effects, including blood pressure changes, vascular leak syndrome, liver dysfunction, neurological changes (cognitive impairment), and high fever (1, 2). These toxic effects require some patients to withdraw from therapy after a limited number of therapy cycles. Nevertheless, HD IL-2 continues to be a treatment of choice for qualified patients, especially for those with metastatic melanoma, because it is one of the only therapies capable of inducing documented durable clinical remission lasting for many years. Thus, specific biomarkers that can identify subsets of patients who are responsive to HD IL-2, and thereby improve patient selection, are needed to refine this form of therapy and make it more attractive to more clinical centers.

Recently, a number of groups have reported that HD IL-2 markedly expands the classic Treg pool, consisting of CD4+CD25+Foxp3+ Tregs (16–19). Some of these studies have attempted to correlate the extent of Treg expansion during IL-2 therapy with clinical outcome and have suggested a negative correlation between a sustained increase in Tregs during multiple IL-2 therapy cycles and progressive disease (17). Tregs inhibit effector CD8+ and CD4+ T cells by suppressing their proliferation or inducing cell death. Moreover, Tregs can also antagonize NK cell–mediated antitumor activity (20–23). However, the exact role of Tregs in HD IL-2 therapy needs to be further defined.

Tregs exist in two main forms: the so-called natural Tregs, originally derived from the thymus, and induced Tregs, generated from peripheral naive CD4+ T cells in the presence of TGF-β and IL-2 (22, 24, 25). However, the phenotypic markers distinguishing these two main Treg types are still unclear. Although previous studies have tracked the appearance of Tregs during IL-2 therapy by using the classic markers CD25, Foxp3, cytotoxic T lymphocyte antigen 4 (CTLA4), glucocorticoid-induced tumor necrosis factor receptor (GITR), and CD127, Tregs may exist in various states of differentiation and activation that may be discernible with use of additional markers. For example, a subset of Tregs may be tumor antigen specific and activated through the TCR before HD IL-2 therapy; these cells may carry specific activation markers reflecting this ongoing antigenic stimulation that clearly separates them from the bulk circulating Treg population. Thus, these previously “activated” tumor-specific Tregs may be induced to further divide by IL-2 treatment.

In this article, we investigated which lymphoid and myeloid subsets were modulated upon HD IL-2 therapy and their possible association with clinical response to allow preidentification of patients who can benefit from this treatment. We performed comprehensive multiparameter flow cytometry analysis to determine the changes in more than 40 different lymphocyte subsets, including subpopulations of Tregs, DCs, and CD4+, CD8+, NK, and B cells in PBMCs from patients treated with HD IL-2 before IL-2 infusion and 2 days after the last infusion of cycle 1 of HD IL-2 therapy. After analyzing the fold changes of each cell subset, we found that CD4+ICOS+ T cell subset, consisting almost exclusively of CD25hi and Foxp3hi Tregs (ICOS+ Tregs), was one of the most rapidly expanding lymphocyte subsets in response to IL-2. We present data characterizing the phenotype of CD4+ICOS+ and ICOS+ Treg subsets during the first cycle of HD IL-2 therapy and their potential as predictive biomarkers.
Results

Activated T cells within a CD4+ICOS+ subset greatly increase during IL-2 therapy. We developed a multicolor FACS staining panel to track changes in multiple lymphocyte subsets in peripheral blood of patients with melanoma during cycle 1 of HD IL-2 therapy. This panel allowed us to track the changes in multiple T cell, B cell, DC, and NK cell lineages before and after HD IL-2 therapy. First, we analyzed the first 9 patients consecutively treated with HD IL-2 (Supplemental Table 1; supplemental material available online with this article; doi: 10.1172/JCI46266DS1). Blood was collected immediately before the first bolus infusion of IL-2 and during the rebound period, which is 2 days after the last IL-2 infusion, when a rapid influx of lymphocytes back into the blood occurs (16, 26, 27). This sample 2 days after IL-2 treatment gives us a “window” into the immediate changes that are induced in patients during the first cycle of IL-2 therapy. A heat diagram of the FACS data shows the fold change in 46 lymphocyte subsets as a percentage of total live lymphocytes (Figure 1A). Strikingly, although minor changes occurred in a number of lymphocyte subsets, some major cell types consistently exhibited markedly high increases in all patients during IL-2 therapy, as indicated by the bright red regions in Figure 1A. One of these cell types was the CD4+ T cells, which consisted of ICOS+, CD25+ICOS+, and CD4+CD25+ICOS+ T cells that coexpressed Foxp3 (Figure 1A).
CD4+ T cells expressing ICOS with phenotypic characteristics of Tregs increFigure 1

CD4+ T cells expressing ICOS with phenotypic characteristics of Tregs increase the most in peripheral blood after HD IL-2 therapy. PBMCs isolated at baseline and 2 days after the last dose of IL-2 during cycle 1 of HD IL-2 therapy from 9 patients (nonresponders) were stained for multiple T, B, and NK cell and DC markers. The percentage of 46 cell subsets in the live lymphocyte gate were determined, and the fold change in the frequency of each indicated cell subset in the lymphocyte gate was calculated by dividing the frequency of cells before HD IL-2 therapy by the frequency after treatment. (A) Changes in the percentage of indicated cell subsets analyzed for all 9 patients (patient numbers are shown at the top of the heat map) were heat mapped based on the fold changes, with the use of an Excel conditional formatting program, as indicated at the bottom of the figure. The major lymphocyte subpopulations corresponding to the different phenotypic marker subsets (left side) are indicated on the right side of the heat diagram. (B) Total numbers of CD4+ICOS+, CD4+CD25+ICOS+, and CD4+CD25+Foxp3+ICOS+ cells before IL-2 and 2 days after cycle 1 of HD IL-2 therapy (after IL-2) are shown for these 9 patients. Total cell numbers were calculated by multiplying the percentage of each subset in the viable lymphocyte gate by the absolute lymphocyte count. Horizontal bars represent median values. Statistical analyses were performed with 2-tailed Wilcoxon matched paired test.

The second major cell type that showed a high increase in all patients was NK cells, with a predominantly CD56hiCD16loPRF1+ NK phenotype (Figure 1A) and more than an 80-fold increase in these cells in some patients (median, 25-fold increase; n = 9). Expansion of NK cells and acute sensitivity of these cells to IL-2, as these cells constitutively express CD25 (IL-2Rα), as well as perforin-induced expression by IL-2 were expected on the basis of previous studies on IL-2–treated patients (28–31). All other lymphocyte subsets exhibited either small increases after IL-2 therapy (less than 2 fold) or a decrease, as shown by the blue regions in Figure 1A. Increased frequency of CD11c+ DCs was seen in some patients (median, 3.6 fold), whereas the frequency of CD19+ B cells consistently decreased after IL-2 therapy by 3 fold to 4 fold.

The CD4+ICOS+ and CD4+CD25+ICOS+ cell subsets increased by a median of 13 fold and 27 fold, respectively. However, the most consistent and highest increase was in the frequency of CD4+CD25+Foxp3+ICOS+ T cells (median, 37 fold). We calculated the change in total number of ICOS+ cells in the CD4+ subset by multiplying the absolute lymphocyte counts per milliliter of blood by the percentage of each subset in the live lymphocyte gate. As shown in Figure 1B, the total number of CD4+ICOS+, CD4+CD25+ICOS+, and CD4+CD25+Foxp3+ICOS+ T cells increased greatly after HD IL-2 therapy. Similar results were seen with the .     . http://www.jci.org/

 

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

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Janet Lee's picture
Replies 5
Last reply 1/13/2014 - 11:19am

I've seen a couple of posts recently about left-over melanoma drugs, as well as cautionary replies about scams, confidentiality, etc. I think this is a very valid topic, and would like to know if there are any "legitimate" ways to donate any of these expensive drugs to the melanoma patients who may be without insurance or are being denied the medicine for whatever reason.

Seems to me there should or could be some sort of clearing house to help others?

Janet Lee

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Bob B.'s picture
Replies 3
Last reply 1/9/2014 - 11:25am
Replies by: lsmith - MRF, Anonymous, BrianP

it's been awhile since I visited.   The site has changed.

 

How do I "search" a previous Topic?

 

Thanks!

 

Bob B.

The Only Good Legend is a Dead Legend.

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hdelancey23's picture
Replies 10
Last reply 12/30/2013 - 11:23pm

I am up visiting my mom for Christmas. And it has been a great time. My mom is doing as well as can be expected. The morphine is really helping in managing her pain at home. She does okay through the day but it is the mornings that are the worst on her. It is hard for her to get up out of bed and very painful for her. I guess it is from the morphine wearing off through the night and it seems like her body is very very stiff. She has consultation for WBR next week and will start next week as well. I am nervous to see how she takes a second dose of it. I am just praying that it might buy some more time to get into the pd1 trials. At this point for me any more Tim that we can get is very precious. She is such a fighter and so strong. Her doctors told her last December that she only had three to six months and now here we are a year later. To all those that are fighting this horrible disease and to family members that are watching their loved ones struggle you can't always go by what the doctors say. Keep fighting and keep hoping.

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lll.ll.lll.ll.lll's picture
Replies 7
Last reply 1/4/2014 - 12:01am

I'm so glad I have found this.. I've been a little lost with all this and seems that nobody really wants to talk about it so I'm hoping I can find some input here.

I started noticing something was wrong back in late Aug early September.. I was tired all the time. I'm physically active and workout five to six days a week and was doing a very physical job at the time but I was really the only one struggling dieting it physically with being so tired.

It was during that time I started to notice a swimy feeling in my head and I was getting confused and angry at almost nothing. I honestly thought I was getting early dementia or had cte.

Two months later I was still tired and having the same issues with my brain.. I would describe it as taking pain killers on an empty stomach and the sick feelings that come with. But I kept brushing it off till one morning I woke with a severe burning feeling on a spot on my back. When I went to look in the mirror it was a dark spot I had had for years and apon touching it it began to ooze dark thick blood.

Being uninsured two days later I found a dermatologist that would perform the biopsy. I told the nurse and the Dr what I had been going through. The Dr only visually looked at my back and said there were a few spots he was concerned about but the one I came in for definitely needed to be biopsied.

A week later the results came back that it was in fact melanoma and it needed to be removed and he recommend I get health insurance to get it taken care of.

Well my insurance wont kick in till the first of the year and other things keep popping up.. I still have the swimy brain only worse now.. I stumble now sometimes when I walk.. I've noticed lymph nodes in my pelvis get larger over the past month or so and now I'm getting pains in the area.. I get a stabbing pain in my diaphragm from time to time and I find it hard to catch my breath..

I've been to the er twice now cause it gets so bad..

My white count is "elevated" and they say it can be from just an infection.. my brain scan had some admoralities but nothing "acute" and my chest xray looked "alright"

I know er and Dr talk all to well and they dance around things.. I guess I'm hoping maybe someone has had similar symptoms

Adam McCurry

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PracticeUpdate: In your view, which development that occurred in 2013 in melanoma research could have the most significant impact on clinical practice?

Dr. Kirshner: The reporting of the results of additional clinical trials of antibodies against the programmed death 1 (PD-1) receptor and ligand (PD-L1).

The most striking of these studies was presented at ASCO 2013 and promptly published by Wolchok et al in The New England Journal of Medicine in July.1 Metastatic melanoma patients treated with the combination of ipilimumab and nivolumab had a disease control rate of over 65%! The majority of responses were major and are predicted to be durable.

Additional reports of T-cell checkpoint inhibition presented at ASCO add to the growing body of evidence that inhibitors of CTLA-4, PD-1, and PD-L1 are effective treatments for melanoma, with a number of long-term survivors. Patients progressing on ipilimumab can respond to nivolumab or even to retreatment with the same drug and schedule.

PracticeUpdate: What specific changes have you observed or do you foresee as a result of this development?

Dr. Kirshner: I expect FDA approval of nivolumab in the next year and the approval of even more checkpoint inhibitors in the near future.

PracticeUpdate: Would you put this development into historical perspective for the practicing physician?

Dr. Kirshner: Not too long ago, treatment options for metastatic melanoma were very limited. Responses to chemotherapy are poor, in general, and toxicity can be substantial. Immunotherapy (interferon and IL-2) is toxic, for the most part, but occasional durable responses were seen, usually in patients with more limited disease.

T-cell checkpoint inhibitors have a different mode of action than prior treatments (blocking inhibition activates T cells for more effective immune destruction of the metastases). These are the most active treatments for metastatic melanoma to date, and toxicities are manageable.

PracticeUpdate: Would you sum up in a single sentence why you chose this development as the top story of the past year?

Dr. Kirshner: The development of new T-cell checkpoint inhibitors (specifically anti-PD-1 and anti-PD-L1) not only adds to the armamentarium of treatments for advanced melanoma, but there are reasons to believe that these drugs will be active in a wide range of malignancies that would respond to immunotherapy.

Reference

  1. Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369(2):122-133.

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Brendan's picture
Replies 3
Last reply 1/1/2014 - 9:09am
Replies by: ReginaTink, Anonymous, POW

Hi Everyone,

I hope the holidays are treating you well.  

I am happy to report that I am now in a PD-1 trial.  I am receiving nivolumab every other Friday for at least five more doses. If I respond then I will receive six additional doses.  The clinical trial is in Tampa and I live in Philadelphia.  I have flown down twice and the bills are already adding up.  USAir and Southwest fly daily and I am going to look into their medical travel programs.

Does anyone know of any agencies, non-profits, etc., that help cancer patients with travel expenses?  The primary expense is obviously airfare, but car rental adds up too.

Thanks and good luck to you,

Brendan

 

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mitchwendy's picture
Replies 2
Last reply 12/31/2013 - 10:40am
Replies by: mitchwendy, sbrooks90

If you had this done, how long did you wait before returning to exercise, specifically running?
 

They say "return to normal activities", but would that include running? I had 5 nodes removed (all free! ) and I did do 20 minutes with walk breaks yesterday and did not have any new swelling or increased pain....

Just curious as to what others experiences were....

 

Thanks!

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arthurjedi007's picture
Replies 4
Last reply 1/1/2014 - 7:34am
Replies by: Anonymous, buffcody, arthurjedi007, ecc26

Got my blood work today before my 3rd dose of ipi(yervoy). Anyone know what a large increase means in eosinophils? 3 weeks ago it was 2.7 with an absolute of .2. Today it is 8.0 with an absolute of .5.

I was also wondering if ipi is working should we also see an increase in our absolute lymphocytes? 3 weeks ago mine was 1.2 and now it is 1.1 so really no change.

Typically my numbers are closely the same so to see a number more than double is odd and has me wondering what's happening. I assume it is a reaction to ipi so that is great but I dunno. My dr did not mention anything about it just said my blood work looks good.

Thanks everyone and I hope the new year is great for all of us mel warriors.

 

 

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SaveMySister's picture
Replies 13
Last reply 1/10/2014 - 8:15am

Hi all,

I haven't posted since shortly after my sister passed away less than one month after being diagnosed with stage 4 melanoma last July. Being that she had no skin abnormalities, I am wondering if we all missed any other warning signs.  If you get a melanoma lesion on your lung, would it cause breathing difficulty? She had a small 'mass' on her lung that they called a cyst, which was detected about 1-1/2 months before her diagnosis. She had had breathing problems which were assumed to be allergy related back in 2011, which never really got under control completely.  (They removed polyps from her sinuses but kept putting her on steroids.)  She was tired a lot and became a caffeine drinker.

Her melanoma was discovered when a large tumor was removed from her lymph node. An MRI of her brain shortly thereafter revealed 11 lesions. I guess what I am trying to figure out, is that are there any warning signs that I can look for to try to catch this very scary form of melanoma that shows up internally? I don't want to spend my 50's and 60's being paranoid that I will be dealt the same fate as my sister. I am getting my skin checked every 6 months, but in my case that may not be enough.

Thanks!

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BrianP's picture
Replies 1
Last reply 12/30/2013 - 9:54pm
Replies by: BrianP

A small subset of patients with supposedly nongenetically driven melanomas respond to molecularly targeted treatment with an MEK inhibitor, according to recent findings released today.

Two novel genetic fusions involving BRAF – PAPSS1-BRAF and TRIM24-BRAF – were present in 2 of 24 (8%) of pan-negative melanoma samples tested. Both BRAF fusions activate the MAPK signaling pathway, and tumors found harboring either genetic fusion were more sensitive to treatment with trametinib than with the BRAF inhibitor vemurafenib, reported Dr. Jeffrey A. Sosman, professor of medicine, director of the melanoma and tumor immunotherapy program, and co-leader of the VICC signal transduction and cell proliferation research program of the Vanderbilt-Ingram Cancer Center in Nashville, Tenn., and his associates.

“About 35% of melanomas are, as of today, considered pan negative, which means they are devoid of any previously known driver mutations in the genes BRAF, NRAS, KIT, GNAQ, and GNA11,” Dr. Sosman explained in a press release issued by the American Association of Cancer Research.

“Our data support the idea that pan-negative cancers are not truly pan negative,” he added, noting the results are “important because they suggest that there probably are other, as yet unidentified, molecular changes that make these melanomas susceptible to drugs that are available right now.”

Dr. Sosman and his associates have spent several years assessing pan-negative tumors for any potential genetic anomalies other than those already known that could offer targets for molecularly driven treatment. Their discovery of PAPSS1-BRAF came from examination of a sample from a 27-year-old woman with stage IIIC malignant melanoma involving almost all the axillary lymph nodes. Despite irradiation and experimental and standard immunotherapies, the patient progressed rapidly and died just 11 months after her diagnosis.

Some of you more technical savy folks might find this article interesting.  Just don't ask me to explain it!

 

The patient’s sample had been genotyped using the, which examines more than 3,000 exons in 182 cancer-related genes and 37 introns and in 14 genes recurrently rearranged in cancer. The assay simultaneously looks for any single nucleotide variants, insertions, deletions, copy number changes, and selected genetic rearrangements.

They found a large genomic deletion in BRAF and a region on chromosome 7 suggesting that two genes were possibly fused together. Subsequent targeted RNA sequencing of complementary DNA identified PAPSS1-BRAF and further studies showed that it activated the MAPK signaling pathway and that this activation was more sensitive to inhibition with a MEK inhibitor than with a BRAF inhibition.

The team then evaluated a further 51 melanoma samples, of which the majority were supposedly pan negative – only eight had BRAF V600 changes and seven had other, non-V600 changes. TRIM24-BRAF was also identified and found to affect the MAPK signalling pathway and be more sensitive to MEK than BRAF inhibition.

The team also analyzed RNA, whole genome, and whole-exome sequencing data from an independent cutaneous dataset available from the Cancer Genome Atlas and found BRAF fusions in two of 49 of pan-negative melanoma cases researchers.

“Collectively, these data suggest that BRAF fusions exist in 4%-8% of pan-negative melanomas,” the researchers reported. “Coupled with the fact that the transforming ability of multiple BRAF fusions has already been established, we believe enough evidence exists to raise awareness that BRAF fusions are present in this ‘pan-negative’ population.”

This could have implications for clinical trials involving therapies that target the MAPK signaling pathway and explain why unexpected clinical responses are sometimes seen with MEK inhibitor therapy. The findings could also help clinicians select patients for MEK-directed therapy.

Dr. Sosman and associates conclude (Clin. Cancer Res. 2013 Dec. 17;19:6696-702): “BRAF fusions represent a new, potentially clinically relevant target in melanomas possibly treatable with kinase inhibitors.”

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WendyD.'s picture
Replies 5
Last reply 12/31/2013 - 3:50pm
Replies by: Anonymous, WendyD., BrianP, Janner

I have to admit once I was diagnosed with melanoma I did what most of us did. I Googled everything I could on melanoma. I wanted to know what I was facing. Well, during all of the research I got confused on something. How can doctors/pathologists stage someone a stage T1a melanoma when there usually isn't a SNB done for thin lesions? How would anyone truly know that someone is a T1a without knowing if the melanoma has spread to nearby lympnodes? Another thing I would like to know is what are the chances of a thin lesion spreading that had no mitosis and no ucleration and was less than 1mm thick? If someone has links to web pages stating percentages of chance of spread I would definitely like to see it. It seems everything I have read so far says it can only truly be a T1a if it hasn't spread, which goes back to how do we truly know if the SNB was never done? Ok sorry for all the questions, but I really want to know this stuff.

In God I Trustsmiley!

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What You Need to Know About Interleukin-2 for Metastatic Melanoma.

"Melanoma." National Comprehensive Cancer Network. V.1.2009. 27 January 2009.

"Proleukin Prescribing Information." Novartis Pharmaceuticals Corp. 27 January 2009.

Smith FO, Downey SG, Klapper JA, et al. Treatment of metastatic melanoma using interleukin-2 alone or in conjunction with vaccines. Clin Cancer Res 2008 14:5610-5618. 27 January 2009.

This overview will arm you with the critical information you need to understand how it works, its effectiveness and its side effects.

Other Names (United States)
Proleukin, aldesleukin
Approved

1998
Description

IL-2 was approved by the Food and Drug Administration for the treatment of metastatic melanoma in 1998.

IL-2 is different than a chemotherapy drug -- it is actually a natural part of your body's immune system. It is a type of messenger molecule called a "cytokine" that is secreted from certain cells to alert other cells about an infectious invader. At least 15 different kinds of interleukins have been discovered since the 1970s: IL-2 is known to specifically stimulate the growth and maturation of two kinds of white blood cells, called "T and B lymphocytes." The IL-2 used to treat metastatic melanoma doesn't come from the body but rather is mass produced, using the techniques of genetic engineering. It has the same properties as the natural version, but it has a slightly different name, aldesleukin.

Evidence for the Effectiveness of Interleukin-2

In the studies that led to approval, 6% of selected patients (those in good physical and mental condition) with metastatic melanoma had a complete response to high-dose IL-2, and 10% had a partial response. A complete response is defined as a long-lasting (10+ years and counting) elimination of the disease, although it is not technically a "cure." Regardless of the terminology, it is the only drug available that even has the possibility of such a profoundly positive and lengthy effect. Responses were observed in patients with a variety of metastases, including in the lung, liver, lymph nodes, soft tissue, adrenal glands and subcutaneous (deep) layers of the skin. IL-2, however, has not previously been recommended for patients with existing brain metastases.

Many clinical trials have been conducted (and are still being conducted) in an attempt to increase the response rates of IL-2 by combining it with other medicines. For example, a study demonstrated higher response rates when IL-2 was given in combination with a vaccine (22%) compared to IL-2 alone (13%). Unfortunately, many attempts to combine IL-2 with various chemotherapy drugs (cisplatin, vinblastine, dacarbazine and others) -- an approach called "biochemotherapy" -- as well as with other drugs (interferon-alfa2b, etc), have thus far shown no significant improvement in the statistic that really counts: survival time.

Use of Interleukin-2

IL-2 is given by a 15-minute IV infusion every 8 hours for 5 days. Each treatment course consists of two 5-day treatment cycles separated by a 9-day rest period, and multiple courses are the norm. You will typically be imaged about a month after finishing your first treatment. If you are responding, you'll likely be offered a second course of treatment for 6 to 12 weeks after finishing the first course. To be eligible for IL-2 treatment, you must be in relatively good physical condition, with good heart, lung, liver and kidney function.

Potential Side Effects

IL-2 has frequent, often serious and sometimes fatal side effects. It should be given in a hospital under the supervision of a qualified physician experienced in the use of anticancer agents. An intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine must be available. The rate of drug-related deaths in clinical trials of metastatic melanoma patients who received IL-2 was 2%.

Many of the side effects are due to "capillary leak," which begins immediately after treatment is started. Capillary leak results in the leakage of proteins out of blood that then causes a decrease in blood pressure. The most common side effects are as follows:

    nausea, vomiting, diarrhea, loss of appetite
    weakness and fatigue
    flu-like symptoms (fever, chills, headache and muscle aches)
    low blood pressure
    general pain, chest pain (angina)
    breathing problems due to fluid in the lungs
    weight gain, fluid retention
    mental effects (paranoia, hallucinations, insomnia)
    itching, peeling skin
    anemia (low red blood cell count)
    low platelet count (increasing the risk of bleeding)
    low white blood cell count
    kidney damage
    mouth sores

These side effects are rarer but have been reported in some people taking IL-2:

    abnormal heart rhythm, heart attack
    respiratory failure
    severe infections
    gastrointestinal bleeding
    thyroid problems
    liver problems
    severe dizziness, fainting

Cautions/Interactions

IL-2 can make the side effects of other drugs and diseases much worse, so tell your doctor if you have:

    kidney problems
    heart disease
    liver disease
    lung disease
    a seizure disorder
    thyroid disorder
    infections
    any allergies
    any immune disorders

Also let your doctor know about any over-the-counter or prescription medications you use, especially corticosteroids, indomethacin, blood pressure drugs, antidepressants, anti-anxiety drugs or other anticancer medications. Do not start or stop any medicine without doctor approval.

Sources:

 

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

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JerryfromFauq's picture
Replies 5
Last reply 1/2/2014 - 3:30am
Replies by: BrianP, JerryfromFauq, Anonymous, JoshF, POW

What You Need to Know About Interleukin-2 for Metastatic Melanoma.

"Melanoma." National Comprehensive Cancer Network. V.1.2009. 27 January 2009.

"Proleukin Prescribing Information." Novartis Pharmaceuticals Corp. 27 January 2009.

Smith FO, Downey SG, Klapper JA, et al. Treatment of metastatic melanoma using interleukin-2 alone or in conjunction with vaccines. Clin Cancer Res 2008 14:5610-5618. 27 January 2009.

This overview will arm you with the critical information you need to understand how it works, its effectiveness and its side effects.

Other Names (United States)
Proleukin, aldesleukin
Approved

1998
Description

IL-2 was approved by the Food and Drug Administration for the treatment of metastatic melanoma in 1998.

IL-2 is different than a chemotherapy drug -- it is actually a natural part of your body's immune system. It is a type of messenger molecule called a "cytokine" that is secreted from certain cells to alert other cells about an infectious invader. At least 15 different kinds of interleukins have been discovered since the 1970s: IL-2 is known to specifically stimulate the growth and maturation of two kinds of white blood cells, called "T and B lymphocytes." The IL-2 used to treat metastatic melanoma doesn't come from the body but rather is mass produced, using the techniques of genetic engineering. It has the same properties as the natural version, but it has a slightly different name, aldesleukin.

Evidence for the Effectiveness of Interleukin-2

In the studies that led to approval, 6% of selected patients (those in good physical and mental condition) with metastatic melanoma had a complete response to high-dose IL-2, and 10% had a partial response. A complete response is defined as a long-lasting (10+ years and counting) elimination of the disease, although it is not technically a "cure." Regardless of the terminology, it is the only drug available that even has the possibility of such a profoundly positive and lengthy effect. Responses were observed in patients with a variety of metastases, including in the lung, liver, lymph nodes, soft tissue, adrenal glands and subcutaneous (deep) layers of the skin. IL-2, however, has not previously been recommended for patients with existing brain metastases.

Many clinical trials have been conducted (and are still being conducted) in an attempt to increase the response rates of IL-2 by combining it with other medicines. For example, a study demonstrated higher response rates when IL-2 was given in combination with a vaccine (22%) compared to IL-2 alone (13%). Unfortunately, many attempts to combine IL-2 with various chemotherapy drugs (cisplatin, vinblastine, dacarbazine and others) -- an approach called "biochemotherapy" -- as well as with other drugs (interferon-alfa2b, etc), have thus far shown no significant improvement in the statistic that really counts: survival time.

Use of Interleukin-2

IL-2 is given by a 15-minute IV infusion every 8 hours for 5 days. Each treatment course consists of two 5-day treatment cycles separated by a 9-day rest period, and multiple courses are the norm. You will typically be imaged about a month after finishing your first treatment. If you are responding, you'll likely be offered a second course of treatment for 6 to 12 weeks after finishing the first course. To be eligible for IL-2 treatment, you must be in relatively good physical condition, with good heart, lung, liver and kidney function.

Potential Side Effects

IL-2 has frequent, often serious and sometimes fatal side effects. It should be given in a hospital under the supervision of a qualified physician experienced in the use of anticancer agents. An intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine must be available. The rate of drug-related deaths in clinical trials of metastatic melanoma patients who received IL-2 was 2%.

Many of the side effects are due to "capillary leak," which begins immediately after treatment is started. Capillary leak results in the leakage of proteins out of blood that then causes a decrease in blood pressure. The most common side effects are as follows:

    nausea, vomiting, diarrhea, loss of appetite
    weakness and fatigue
    flu-like symptoms (fever, chills, headache and muscle aches)
    low blood pressure
    general pain, chest pain (angina)
    breathing problems due to fluid in the lungs
    weight gain, fluid retention
    mental effects (paranoia, hallucinations, insomnia)
    itching, peeling skin
    anemia (low red blood cell count)
    low platelet count (increasing the risk of bleeding)
    low white blood cell count
    kidney damage
    mouth sores

These side effects are rarer but have been reported in some people taking IL-2:

    abnormal heart rhythm, heart attack
    respiratory failure
    severe infections
    gastrointestinal bleeding
    thyroid problems
    liver problems
    severe dizziness, fainting

Cautions/Interactions

IL-2 can make the side effects of other drugs and diseases much worse, so tell your doctor if you have:

    kidney problems
    heart disease
    liver disease
    lung disease
    a seizure disorder
    thyroid disorder
    infections
    any allergies
    any immune disorders

Also let your doctor know about any over-the-counter or prescription medications you use, especially corticosteroids, indomethacin, blood pressure drugs, antidepressants, anti-anxiety drugs or other anticancer medications. Do not start or stop any medicine without doctor approval.

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

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