IL-2 and immune system

This topic has 30 replies, 5 voices, and was last updated 11 years, 8 months ago by JerryfromFauq.

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- December 28, 2013 at 9:06 am
- Quote
JerryfromFauq
Participant
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/

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Replies

- - December 28, 2013 at 9:11 am
  - Quote
  JerryfromFauq
  Participant
  Will this work? Jci.org/articles/view/46266
- - December 28, 2013 at 9:11 am
  - Quote
  JerryfromFauq
  Participant
  Will this work? Jci.org/articles/view/46266
- - December 28, 2013 at 9:11 am
  - Quote
  JerryfromFauq
  Participant
  Will this work? Jci.org/articles/view/46266
- - December 28, 2013 at 4:00 pm
  - Quote
  JoshF
  Participant
  So what does this all mean? As someone who will be receiving IL-2 on Jan 6… I'm very interested.
- - December 28, 2013 at 4:00 pm
  - Quote
  JoshF
  Participant
  So what does this all mean? As someone who will be receiving IL-2 on Jan 6… I'm very interested.
  - December 29, 2013 at 5:03 am
    
    Quote
    POW
    Participant
    
    Hi, Josh-
    
    This article should have no impact on your decision to get IL-2. As for all melanoma treatments, these researchers are trying to figure out why some patients respond well to IL-2 and have long-term success while other patients seem to get no benefit.
    
    These authors are looking at 40 different types of T cells and asking which type(s) of T cells are being stimulated by IL-2. They did identify certain types of T cells that get stimulated to proliferate by IL-2, but they found no correlataion between increased number of those particular T cell types and patient survival.
    
    So basically, they did a lot of work and added to the knowledge base but did not yet figure out which patients will benefit from IL-2 treatment. (sigh!)
  - December 29, 2013 at 5:03 am
    
    Quote
    POW
    Participant
    
    Hi, Josh-
    
    This article should have no impact on your decision to get IL-2. As for all melanoma treatments, these researchers are trying to figure out why some patients respond well to IL-2 and have long-term success while other patients seem to get no benefit.
    
    These authors are looking at 40 different types of T cells and asking which type(s) of T cells are being stimulated by IL-2. They did identify certain types of T cells that get stimulated to proliferate by IL-2, but they found no correlataion between increased number of those particular T cell types and patient survival.
    
    So basically, they did a lot of work and added to the knowledge base but did not yet figure out which patients will benefit from IL-2 treatment. (sigh!)
  - December 29, 2013 at 5:21 am
    
    Quote
    JoshF
    Participant
    
    Thanks….didn't quite get what result if study was. I'm in trial through Prometheus labs looking at combo therapy with ipi and il2. Just finished ipi which went pretty well. Ended up with hypothyroid, itchy itchy itchy legs/rash and stomach cramping at times. Finished that dec 11 and had scan dec 20 which doc was very pleased with. Wouldn't change my mind on il2….think it's important to first try and beat this once and for all. Secondly, hopefully add some data as to effectiveness of combo therapy for other patients down the line. We all need more weapons!!!!
    
    Josh
  - December 29, 2013 at 5:21 am
    
    Quote
    JoshF
    Participant
    
    Thanks….didn't quite get what result if study was. I'm in trial through Prometheus labs looking at combo therapy with ipi and il2. Just finished ipi which went pretty well. Ended up with hypothyroid, itchy itchy itchy legs/rash and stomach cramping at times. Finished that dec 11 and had scan dec 20 which doc was very pleased with. Wouldn't change my mind on il2….think it's important to first try and beat this once and for all. Secondly, hopefully add some data as to effectiveness of combo therapy for other patients down the line. We all need more weapons!!!!
    
    Josh
  - December 29, 2013 at 5:21 am
    
    Quote
    JoshF
    Participant
    
    Thanks….didn't quite get what result if study was. I'm in trial through Prometheus labs looking at combo therapy with ipi and il2. Just finished ipi which went pretty well. Ended up with hypothyroid, itchy itchy itchy legs/rash and stomach cramping at times. Finished that dec 11 and had scan dec 20 which doc was very pleased with. Wouldn't change my mind on il2….think it's important to first try and beat this once and for all. Secondly, hopefully add some data as to effectiveness of combo therapy for other patients down the line. We all need more weapons!!!!
    
    Josh
  - December 29, 2013 at 5:03 am
    
    Quote
    POW
    Participant
    
    Hi, Josh-
    
    This article should have no impact on your decision to get IL-2. As for all melanoma treatments, these researchers are trying to figure out why some patients respond well to IL-2 and have long-term success while other patients seem to get no benefit.
    
    These authors are looking at 40 different types of T cells and asking which type(s) of T cells are being stimulated by IL-2. They did identify certain types of T cells that get stimulated to proliferate by IL-2, but they found no correlataion between increased number of those particular T cell types and patient survival.
    
    So basically, they did a lot of work and added to the knowledge base but did not yet figure out which patients will benefit from IL-2 treatment. (sigh!)
- - December 28, 2013 at 4:00 pm
  - Quote
  JoshF
  Participant
  So what does this all mean? As someone who will be receiving IL-2 on Jan 6… I'm very interested.
- - December 29, 2013 at 1:27 am
  - Quote
  Joannezaras
  Participant
  Hi Jerry
  
  my mom has recently been diagnosed and had surgery for Mucusal Melonoma if the parasinus. We are just at the beginning of this journey. I was reading about your treatment and wondered if you knew if it was happening in Canada as well? We have our first appointment with the oncologist coming up and a post op meeting with the surgeon with radiation starting shortly. Where do we start with getting tested for the drug you are taking?
- - December 29, 2013 at 1:27 am
  - Quote
  Joannezaras
  Participant
  Hi Jerry
  
  my mom has recently been diagnosed and had surgery for Mucusal Melonoma if the parasinus. We are just at the beginning of this journey. I was reading about your treatment and wondered if you knew if it was happening in Canada as well? We have our first appointment with the oncologist coming up and a post op meeting with the surgeon with radiation starting shortly. Where do we start with getting tested for the drug you are taking?
  - December 29, 2013 at 2:59 pm
    
    Quote
    Cooper
    Participant
    
    Seems like a waste of work and money since IL2 doesn't work for 94% of patients. LIke to see the old drugs give way to the new ones that don't harm the body so much and you don't have to spend time in the Intensive Care Unit to get the drug. So if they do come up with a test it will still only benefit 5% of patients. Resources get wasted on old stuff because of the money interest to keep it alive.
  - December 29, 2013 at 2:59 pm
    
    Quote
    Cooper
    Participant
    
    Seems like a waste of work and money since IL2 doesn't work for 94% of patients. LIke to see the old drugs give way to the new ones that don't harm the body so much and you don't have to spend time in the Intensive Care Unit to get the drug. So if they do come up with a test it will still only benefit 5% of patients. Resources get wasted on old stuff because of the money interest to keep it alive.
  - December 30, 2013 at 3:21 pm
    
    Quote
    POW
    Participant
    
    I understand your feeling that continuing to work with the older treatments is a waste of time and money. However, I see things a little differently.
    
    Right now, there are NO melanoma treatments that work for 100% of the patients– far from it. It is also a waste of time and money to treat people with these expensive drugs and then find out that the drugs didn't work. Even worse, the non-responder patients suffer weeks and months of toxic side-effects and "scanxiety" and all the time their melanomas are continuing to proliferate. This "shotgun" approach is a bad deal all around.
    
    That is why reseachers are putting a lot of time and thought and money (both private sector and government grants) into trying to pin down exactly what makes a drug work well in some patients and not in others. Eventually, they hope to tailor just the right treatment to just the right patient so that we can approach the goal of 100% effectiveness for everybody. I know that seems like a pipedream right now, but basic research like this is "adding to the knowledge base" that will get us there some day. IL-2 may be just the right treatment for some people; the trick is to figure out which people.
    
    By the way, pharmaceutical companies are also very anxious to figure out who will respond to what drugs so that their clinical trials will be faster and cheaper. Right now, if they need to have 500 "responder" patients to complete a clinical trial, they may have to recruit 1500 or more to reach that goal. If (as with the BRAF inhibitors) they know in advance that certain patients will or will not respond, they can focus just on the appropriate patients, recruit and treat fewer to reach their goal, and get the results in front of the FDA much faster. Then they can start selling the drugs sooner and make their investors happy.
  - December 30, 2013 at 3:21 pm
    
    Quote
    POW
    Participant
    
    I understand your feeling that continuing to work with the older treatments is a waste of time and money. However, I see things a little differently.
    
    Right now, there are NO melanoma treatments that work for 100% of the patients– far from it. It is also a waste of time and money to treat people with these expensive drugs and then find out that the drugs didn't work. Even worse, the non-responder patients suffer weeks and months of toxic side-effects and "scanxiety" and all the time their melanomas are continuing to proliferate. This "shotgun" approach is a bad deal all around.
    
    That is why reseachers are putting a lot of time and thought and money (both private sector and government grants) into trying to pin down exactly what makes a drug work well in some patients and not in others. Eventually, they hope to tailor just the right treatment to just the right patient so that we can approach the goal of 100% effectiveness for everybody. I know that seems like a pipedream right now, but basic research like this is "adding to the knowledge base" that will get us there some day. IL-2 may be just the right treatment for some people; the trick is to figure out which people.
    
    By the way, pharmaceutical companies are also very anxious to figure out who will respond to what drugs so that their clinical trials will be faster and cheaper. Right now, if they need to have 500 "responder" patients to complete a clinical trial, they may have to recruit 1500 or more to reach that goal. If (as with the BRAF inhibitors) they know in advance that certain patients will or will not respond, they can focus just on the appropriate patients, recruit and treat fewer to reach their goal, and get the results in front of the FDA much faster. Then they can start selling the drugs sooner and make their investors happy.
  - December 30, 2013 at 3:21 pm
    
    Quote
    POW
    Participant
    
    I understand your feeling that continuing to work with the older treatments is a waste of time and money. However, I see things a little differently.
    
    Right now, there are NO melanoma treatments that work for 100% of the patients– far from it. It is also a waste of time and money to treat people with these expensive drugs and then find out that the drugs didn't work. Even worse, the non-responder patients suffer weeks and months of toxic side-effects and "scanxiety" and all the time their melanomas are continuing to proliferate. This "shotgun" approach is a bad deal all around.
    
    That is why reseachers are putting a lot of time and thought and money (both private sector and government grants) into trying to pin down exactly what makes a drug work well in some patients and not in others. Eventually, they hope to tailor just the right treatment to just the right patient so that we can approach the goal of 100% effectiveness for everybody. I know that seems like a pipedream right now, but basic research like this is "adding to the knowledge base" that will get us there some day. IL-2 may be just the right treatment for some people; the trick is to figure out which people.
    
    By the way, pharmaceutical companies are also very anxious to figure out who will respond to what drugs so that their clinical trials will be faster and cheaper. Right now, if they need to have 500 "responder" patients to complete a clinical trial, they may have to recruit 1500 or more to reach that goal. If (as with the BRAF inhibitors) they know in advance that certain patients will or will not respond, they can focus just on the appropriate patients, recruit and treat fewer to reach their goal, and get the results in front of the FDA much faster. Then they can start selling the drugs sooner and make their investors happy.
  - December 30, 2013 at 7:52 pm
    
    Quote
    JerryfromFauq
    Participant
    
    Lynn, keep attacking while hiding your name. You said the same thing on the other board and all except one that has had IK-2 said that they would gladly do it again.    You are very incorrect to state that IL-2 only benefits 5% of patients. I have never seen any Peer Reviewed Journal articles that say that. IL-2 helped between 15 and 23 % of across the board melanoma patients in the trials used for FDA approval. 15% was the lowest partial success rate in the trials. It does not have as long lasting ill effects as IPI or even PD-1 (Most IL-2 ill effects are gone in about a week. As we discussed with you, I have had friends have to spend several months in the hospital from IPI side effects.
              IL-2 responses are determined much quicker than in Ipi. Il-2 has about the same overall response rate as IPI in most trials and so far IL-2 has shown a longer "Cure" time than IPI. OLD stuff, like old people still often have a benefit,ispite of your belief in only PD-1. PD-1 does help a larger % of people than IL-2, and is great to try first. It still only helps less than 50% of ALL melanoma patients.
    
         Recent NIH studies/publications have stated that NRAS mutation patients have a 47% positive response rate to IL-2, similar to PD-1. Several papers have been published lately (past 6 months) that are helping to cherrypick more of whom IL-2 will help and what cases it is not likely to help. Other treatments have been shown to be more effective following "failure" of IL-2 than when used as stand alone treatments. While it is not for everyone, WHAT IS? My Gleevec targeted treatment is much more expensive than my 49 bags over 6 weeks of IL-2 was.
  - December 30, 2013 at 7:52 pm
    
    Quote
    JerryfromFauq
    Participant
    
    Lynn, keep attacking while hiding your name. You said the same thing on the other board and all except one that has had IK-2 said that they would gladly do it again.    You are very incorrect to state that IL-2 only benefits 5% of patients. I have never seen any Peer Reviewed Journal articles that say that. IL-2 helped between 15 and 23 % of across the board melanoma patients in the trials used for FDA approval. 15% was the lowest partial success rate in the trials. It does not have as long lasting ill effects as IPI or even PD-1 (Most IL-2 ill effects are gone in about a week. As we discussed with you, I have had friends have to spend several months in the hospital from IPI side effects.
              IL-2 responses are determined much quicker than in Ipi. Il-2 has about the same overall response rate as IPI in most trials and so far IL-2 has shown a longer "Cure" time than IPI. OLD stuff, like old people still often have a benefit,ispite of your belief in only PD-1. PD-1 does help a larger % of people than IL-2, and is great to try first. It still only helps less than 50% of ALL melanoma patients.
    
         Recent NIH studies/publications have stated that NRAS mutation patients have a 47% positive response rate to IL-2, similar to PD-1. Several papers have been published lately (past 6 months) that are helping to cherrypick more of whom IL-2 will help and what cases it is not likely to help. Other treatments have been shown to be more effective following "failure" of IL-2 than when used as stand alone treatments. While it is not for everyone, WHAT IS? My Gleevec targeted treatment is much more expensive than my 49 bags over 6 weeks of IL-2 was.
  - December 30, 2013 at 7:52 pm
    
    Quote
    JerryfromFauq
    Participant
    
    Lynn, keep attacking while hiding your name. You said the same thing on the other board and all except one that has had IK-2 said that they would gladly do it again.    You are very incorrect to state that IL-2 only benefits 5% of patients. I have never seen any Peer Reviewed Journal articles that say that. IL-2 helped between 15 and 23 % of across the board melanoma patients in the trials used for FDA approval. 15% was the lowest partial success rate in the trials. It does not have as long lasting ill effects as IPI or even PD-1 (Most IL-2 ill effects are gone in about a week. As we discussed with you, I have had friends have to spend several months in the hospital from IPI side effects.
              IL-2 responses are determined much quicker than in Ipi. Il-2 has about the same overall response rate as IPI in most trials and so far IL-2 has shown a longer "Cure" time than IPI. OLD stuff, like old people still often have a benefit,ispite of your belief in only PD-1. PD-1 does help a larger % of people than IL-2, and is great to try first. It still only helps less than 50% of ALL melanoma patients.
    
         Recent NIH studies/publications have stated that NRAS mutation patients have a 47% positive response rate to IL-2, similar to PD-1. Several papers have been published lately (past 6 months) that are helping to cherrypick more of whom IL-2 will help and what cases it is not likely to help. Other treatments have been shown to be more effective following "failure" of IL-2 than when used as stand alone treatments. While it is not for everyone, WHAT IS? My Gleevec targeted treatment is much more expensive than my 49 bags over 6 weeks of IL-2 was.
  - December 31, 2013 at 4:08 am
    
    Quote
    Joannezaras
    Participant
    
    Hi Jerry
    
    so you have been successful in shrinking tumors with your treatment? Do they have this trial in Canada? What test do you take to see if you will respond to the treatment?
  - December 31, 2013 at 4:08 am
    
    Quote
    Joannezaras
    Participant
    
    Hi Jerry
    
    so you have been successful in shrinking tumors with your treatment? Do they have this trial in Canada? What test do you take to see if you will respond to the treatment?
  - December 31, 2013 at 4:08 am
    
    Quote
    Joannezaras
    Participant
    
    Hi Jerry
    
    so you have been successful in shrinking tumors with your treatment? Do they have this trial in Canada? What test do you take to see if you will respond to the treatment?
  - January 1, 2014 at 8:56 am
    
    Quote
    JerryfromFauq
    Participant
    
    Limited success as far as shrinking my tumors. Most (if not all of the C-kit targeted chemo' are considered cytostatic drugs.versus Apoptotic (Apoptosis) drugs.
    
    cytostagic drugs = stop cell reproduction
    
    Apoptosis = normal (pre-programed) cell death.
    
    Check out:
    
            http://www.ncbi.nlm.nih.gov/pubmed/22513068
    
            http://www.cancer.gov/clinicaltrials
    
    My melanoma is c-kit mucosal melanoma. I went from clear lungs in a mid Jan 2007 PET/CT scan to having innumerable lung tumors in a late Feb 2007 Lung CT scan. I was essentially stable on IL-2 for 20 months. Then had innumerable additiional new lung tumor between Dec 2008 and March 2009 and additional tumors elsewher. Inspite of the lack of approval for Gleevec by the FDA for melanoma, My Melanoma specialist, based on the one published peer reviewed publication of Gleevec working on c-kit (and work being done by Dr Wen Jen Hwu at MDA), prescribed it off-label for me. My tumors became stable within 30 days and have remained stable for another 2 1/2 years.
    
       Since that time there has been much more work and trials fo drugs targged at the C-kit mutations. I strongly recommend getting the oncoprotein stain test (The first test for c-kit – can be done by any local lab). If positive, a c-kit mutation test can be conducted by a specialized lab.
    
    Below is information about drugs that help when one has the c-kit oncoprotein overexprssion and the c-kit DNA mutations.
    
    http://mmdm.cancercommons.org/ml/index.php/C-KIT
    
    Activating c-KIT mutations have been implicated in a variety of cancers (Lennartsson 2005) starting with GIST (Gastrointestinal stromal tumors) and CML (Chronic Myelogenous Leukemia). Because of this, there are both approved drugs and drugs in clinical development that target c-KIT including Imatinib, Sunitib, Nilotinib and Dasatanib.
    
    In 2006, Boris Bastian's group conducted a systematic study evaluating the frequency of c-KIT aberrations in melanoma and found mutations and/or copy number increases in 39% of mucosal, 36% of acral and 28% of melanomas on chronically sun-damaged skins but not in melanomas on skin without chronic sun damage (Curtis 2006). Several additional studies have investigated frequency of c-KIT aberrations since and are summarized below. Also, 30% of melanoma with c-KIT mutations also show increased copy number/amplification of c-KIT.
    
    c-KIT aberrations in melanoma (Woodman 2010)
    
    Type of melanoma
    Copy number
    Mutations
    
    Acral
    24%
    
    Mucosal- All
    26%
    
    Mucosal- Head & neck
    
    12%
    
    Mucosal- Geritourinary
    
    27%
    
    Mucosal- Anorectal
    
    12%
    
    c-KIT is increasingly considered a leading therapeutic target for melanoma. So far, supporting data has primarily come from case reports and small studies (Hodi 2008, Lutzky 2008, Satzger 2010). However, both approved and new drugs are being testing in melanoma with c-KIT aberrations and results are awaited
    
    Drugs Targeting C-Kit
    
    Drug Class
    Company
    HasDevelopmentStatus
    Clinical Trial
    
    Dasatinib
    C-KIT inhibitors
    Bristol-Myers Squibb
    Approved for chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)
    NCT01092728
    NCT00436605
    NCT00597038
    NCT00792545
    
    Gleevec
    C-KIT inhibitors
    Novartis
    Approved for Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML), Kit (CD117)–positive gastrointestinal stromal tumors (GIST)
    NCT00424515
    NCT00470470
    NCT00667953
    NCT00881049
    NCT00421317
    NCT01046487
    
    Sutent
    C-KIT inhibitors
    Pfizer
    Approved for advanced kidney cancer and Gleevec-resistant GIST
    NCT00631618
    NCT00577382
    NCT00859326
    NCT01216657
    NCT01005472
    NCT00489944
    
    Tasigna
    C-KIT inhibitors
    Novartis
    Approved for drug-resistant Chronic Myeloid Leukemia (CML)
    NCT00788775
    NCT01168050
    NCT01028222
    NCT01099514
    
    Pathway
    c-KIT pathway
    
    Technology
    Targeted sequencing
    
    Vendors
    Arup, Fox Chase, Caris, Mayo Clinic, MPLN, TML, UCSF
    
    DrugClass
    c-KIT inhibitors
    
    Comments
    
    Relevant Subtypes: Subtype 2.1
    
    Relevant Trials:
    
    Trials
    Status
    Title
    
    NCT00421317
    Recruiting
    Imatinib in Adult Patients With Metastatic Ocular Melanoma
    
    NCT00424515
    Recruiting
    Imatinib in Patients With Mucosal or Acral/Lentiginous Melanoma
    
    NCT00436605
    Active but not recruiting
    Dasatinib in Treating Patients With Stage III Melanoma That Cannot Be Removed By Surgery or Stage IV Melanoma
    
    NCT00470470
    Recruiting
    Imatinib Mesylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery
    
    NCT00489944
    Recruiting
    Sunitinib, Tamoxifen, and Cisplatin in Treating Patients With High-Risk Ocular Melanoma
    
    NCT00577382
    Recruiting
    SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma
    
    NCT00597038
    Active, not recruiting
    A Phase I/II Study of Dasatinib and Dacarbazine
    
    NCT00631618
    Recruiting
    Clinical Trial of Sutent to Treat Metastatic Melanoma
    
    NCT00667953
    Active not recruiting
    Study of Temzolomide and Gleevec in Advanced Melanoma
    
    NCT00700882
    Suspended
    Dasatinib in Treating Patients With Locally Advanced or Metastatic Mucosal Melanoma, Acral Melanoma, or Solar Melanoma That Cannot Be Removed By Surgery
    
    NCT00788775
    Recruiting
    Nilotinib in TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral, or Chronically Sun Damaged Melanoma
    
    NCT00792545
    Recruiting
    Dasatinib and Bevacizumab in Treating Patients With Solid Tumors That Are Metastatic or Cannot be Removed by Surgery
    
    NCT00859326
    Recruiting
    Combination of Temozolomide and Sunitinib in Treatment of Patients With Metastatic and Unresectable Malignant Melanoma
    
    NCT00881049
    Completed
    Trial of Imatinib (Gleevec®) in Selected Patients With Metastatic Melanoma
    
    NCT01005472
    Active not recruiting
    Temozolomide and Sunitinib Malate in Treating Patients With Stage III or Stage IV Malignant Melanoma
    
    NCT01028222
    Recruiting
    A Study of AMNN107 Against Dacarbazine (DTIC) in the Treatment of Metastatic and/or Inoperable Melanoma Harboring a c-Kit Mutation (TEAM)
    
    NCT01046487
    Recruiting
    Imatinib Mesylate And Cyclophosphamide In Metronomic Administration: Dose Escalation Study Of Imatinib Mesylate (PALANGI3)
    
    NCT01092728
    Not yet recruiting
    Treatment With Dasatinib in Patients With Acral Lentiginous, Mucosal, or Chronic Sun-damaged Melanoma
    
    NCT01099514
    Recruiting
    Study of Nilotinib in Metastatic Melanoma With KIT Aberrations
    
    NCT01168050
    Recruiting
    Efficacy of Nilotinib in First or Second Line Treatment of Primary Melanomas Stage III Unresectable Melanomas.
    
    NCT01216657
    Recruiting
    Trial of Single Agent Sunitinib for Patients With Chemo-refractory Metastatic Melanoma
    
    **********************************************************
    
    Also look at;
    
    http://oncologystat.com/journals/journal_scans/KIT_as_a_Therapeutic_Targ…
    
    http://www.melanoma.org/comment/reply/26098/71256
    
    Even if one does not have the C-kit nor BRAF (they are mutually exlusive) One cannot ubequivalently state that "chemo doesn't touch melanoma." There are many chemo's that have made some melanoma patients NED or else slowed their disease (Most only in the 1-3% range). The problem is that we have not yet learned why they work on the few that they do work on.
    
       IL-2 and Ipi (Yervoy), Immunotherapy treatments (not considered chemo), have a record of helpiing around 20% of across the board melanoma stage IV patients. Again they don 't know exactly why, but these broad spectrum treatments can be effective for many. So far IL-2 has the highest long term "remission/cure" rate for about 5% of stage IV patients.
    
    *******************************************
    
    My email add is: [email protected]
  - January 1, 2014 at 8:56 am
    
    Quote
    JerryfromFauq
    Participant
    
    Limited success as far as shrinking my tumors. Most (if not all of the C-kit targeted chemo' are considered cytostatic drugs.versus Apoptotic (Apoptosis) drugs.
    
    cytostagic drugs = stop cell reproduction
    
    Apoptosis = normal (pre-programed) cell death.
    
    Check out:
    
            http://www.ncbi.nlm.nih.gov/pubmed/22513068
    
            http://www.cancer.gov/clinicaltrials
    
    My melanoma is c-kit mucosal melanoma. I went from clear lungs in a mid Jan 2007 PET/CT scan to having innumerable lung tumors in a late Feb 2007 Lung CT scan. I was essentially stable on IL-2 for 20 months. Then had innumerable additiional new lung tumor between Dec 2008 and March 2009 and additional tumors elsewher. Inspite of the lack of approval for Gleevec by the FDA for melanoma, My Melanoma specialist, based on the one published peer reviewed publication of Gleevec working on c-kit (and work being done by Dr Wen Jen Hwu at MDA), prescribed it off-label for me. My tumors became stable within 30 days and have remained stable for another 2 1/2 years.
    
       Since that time there has been much more work and trials fo drugs targged at the C-kit mutations. I strongly recommend getting the oncoprotein stain test (The first test for c-kit – can be done by any local lab). If positive, a c-kit mutation test can be conducted by a specialized lab.
    
    Below is information about drugs that help when one has the c-kit oncoprotein overexprssion and the c-kit DNA mutations.
    
    http://mmdm.cancercommons.org/ml/index.php/C-KIT
    
    Activating c-KIT mutations have been implicated in a variety of cancers (Lennartsson 2005) starting with GIST (Gastrointestinal stromal tumors) and CML (Chronic Myelogenous Leukemia). Because of this, there are both approved drugs and drugs in clinical development that target c-KIT including Imatinib, Sunitib, Nilotinib and Dasatanib.
    
    In 2006, Boris Bastian's group conducted a systematic study evaluating the frequency of c-KIT aberrations in melanoma and found mutations and/or copy number increases in 39% of mucosal, 36% of acral and 28% of melanomas on chronically sun-damaged skins but not in melanomas on skin without chronic sun damage (Curtis 2006). Several additional studies have investigated frequency of c-KIT aberrations since and are summarized below. Also, 30% of melanoma with c-KIT mutations also show increased copy number/amplification of c-KIT.
    
    c-KIT aberrations in melanoma (Woodman 2010)
    
    Type of melanoma
    Copy number
    Mutations
    
    Acral
    24%
    
    Mucosal- All
    26%
    
    Mucosal- Head & neck
    
    12%
    
    Mucosal- Geritourinary
    
    27%
    
    Mucosal- Anorectal
    
    12%
    
    c-KIT is increasingly considered a leading therapeutic target for melanoma. So far, supporting data has primarily come from case reports and small studies (Hodi 2008, Lutzky 2008, Satzger 2010). However, both approved and new drugs are being testing in melanoma with c-KIT aberrations and results are awaited
    
    Drugs Targeting C-Kit
    
    Drug Class
    Company
    HasDevelopmentStatus
    Clinical Trial
    
    Dasatinib
    C-KIT inhibitors
    Bristol-Myers Squibb
    Approved for chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)
    NCT01092728
    NCT00436605
    NCT00597038
    NCT00792545
    
    Gleevec
    C-KIT inhibitors
    Novartis
    Approved for Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML), Kit (CD117)–positive gastrointestinal stromal tumors (GIST)
    NCT00424515
    NCT00470470
    NCT00667953
    NCT00881049
    NCT00421317
    NCT01046487
    
    Sutent
    C-KIT inhibitors
    Pfizer
    Approved for advanced kidney cancer and Gleevec-resistant GIST
    NCT00631618
    NCT00577382
    NCT00859326
    NCT01216657
    NCT01005472
    NCT00489944
    
    Tasigna
    C-KIT inhibitors
    Novartis
    Approved for drug-resistant Chronic Myeloid Leukemia (CML)
    NCT00788775
    NCT01168050
    NCT01028222
    NCT01099514
    
    Pathway
    c-KIT pathway
    
    Technology
    Targeted sequencing
    
    Vendors
    Arup, Fox Chase, Caris, Mayo Clinic, MPLN, TML, UCSF
    
    DrugClass
    c-KIT inhibitors
    
    Comments
    
    Relevant Subtypes: Subtype 2.1
    
    Relevant Trials:
    
    Trials
    Status
    Title
    
    NCT00421317
    Recruiting
    Imatinib in Adult Patients With Metastatic Ocular Melanoma
    
    NCT00424515
    Recruiting
    Imatinib in Patients With Mucosal or Acral/Lentiginous Melanoma
    
    NCT00436605
    Active but not recruiting
    Dasatinib in Treating Patients With Stage III Melanoma That Cannot Be Removed By Surgery or Stage IV Melanoma
    
    NCT00470470
    Recruiting
    Imatinib Mesylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery
    
    NCT00489944
    Recruiting
    Sunitinib, Tamoxifen, and Cisplatin in Treating Patients With High-Risk Ocular Melanoma
    
    NCT00577382
    Recruiting
    SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma
    
    NCT00597038
    Active, not recruiting
    A Phase I/II Study of Dasatinib and Dacarbazine
    
    NCT00631618
    Recruiting
    Clinical Trial of Sutent to Treat Metastatic Melanoma
    
    NCT00667953
    Active not recruiting
    Study of Temzolomide and Gleevec in Advanced Melanoma
    
    NCT00700882
    Suspended
    Dasatinib in Treating Patients With Locally Advanced or Metastatic Mucosal Melanoma, Acral Melanoma, or Solar Melanoma That Cannot Be Removed By Surgery
    
    NCT00788775
    Recruiting
    Nilotinib in TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral, or Chronically Sun Damaged Melanoma
    
    NCT00792545
    Recruiting
    Dasatinib and Bevacizumab in Treating Patients With Solid Tumors That Are Metastatic or Cannot be Removed by Surgery
    
    NCT00859326
    Recruiting
    Combination of Temozolomide and Sunitinib in Treatment of Patients With Metastatic and Unresectable Malignant Melanoma
    
    NCT00881049
    Completed
    Trial of Imatinib (Gleevec®) in Selected Patients With Metastatic Melanoma
    
    NCT01005472
    Active not recruiting
    Temozolomide and Sunitinib Malate in Treating Patients With Stage III or Stage IV Malignant Melanoma
    
    NCT01028222
    Recruiting
    A Study of AMNN107 Against Dacarbazine (DTIC) in the Treatment of Metastatic and/or Inoperable Melanoma Harboring a c-Kit Mutation (TEAM)
    
    NCT01046487
    Recruiting
    Imatinib Mesylate And Cyclophosphamide In Metronomic Administration: Dose Escalation Study Of Imatinib Mesylate (PALANGI3)
    
    NCT01092728
    Not yet recruiting
    Treatment With Dasatinib in Patients With Acral Lentiginous, Mucosal, or Chronic Sun-damaged Melanoma
    
    NCT01099514
    Recruiting
    Study of Nilotinib in Metastatic Melanoma With KIT Aberrations
    
    NCT01168050
    Recruiting
    Efficacy of Nilotinib in First or Second Line Treatment of Primary Melanomas Stage III Unresectable Melanomas.
    
    NCT01216657
    Recruiting
    Trial of Single Agent Sunitinib for Patients With Chemo-refractory Metastatic Melanoma
    
    **********************************************************
    
    Also look at;
    
    http://oncologystat.com/journals/journal_scans/KIT_as_a_Therapeutic_Targ…
    
    http://www.melanoma.org/comment/reply/26098/71256
    
    Even if one does not have the C-kit nor BRAF (they are mutually exlusive) One cannot ubequivalently state that "chemo doesn't touch melanoma." There are many chemo's that have made some melanoma patients NED or else slowed their disease (Most only in the 1-3% range). The problem is that we have not yet learned why they work on the few that they do work on.
    
       IL-2 and Ipi (Yervoy), Immunotherapy treatments (not considered chemo), have a record of helpiing around 20% of across the board melanoma stage IV patients. Again they don 't know exactly why, but these broad spectrum treatments can be effective for many. So far IL-2 has the highest long term "remission/cure" rate for about 5% of stage IV patients.
    
    *******************************************
    
    My email add is: [email protected]
  - January 1, 2014 at 8:56 am
    
    Quote
    JerryfromFauq
    Participant
    
    Limited success as far as shrinking my tumors. Most (if not all of the C-kit targeted chemo' are considered cytostatic drugs.versus Apoptotic (Apoptosis) drugs.
    
    cytostagic drugs = stop cell reproduction
    
    Apoptosis = normal (pre-programed) cell death.
    
    Check out:
    
            http://www.ncbi.nlm.nih.gov/pubmed/22513068
    
            http://www.cancer.gov/clinicaltrials
    
    My melanoma is c-kit mucosal melanoma. I went from clear lungs in a mid Jan 2007 PET/CT scan to having innumerable lung tumors in a late Feb 2007 Lung CT scan. I was essentially stable on IL-2 for 20 months. Then had innumerable additiional new lung tumor between Dec 2008 and March 2009 and additional tumors elsewher. Inspite of the lack of approval for Gleevec by the FDA for melanoma, My Melanoma specialist, based on the one published peer reviewed publication of Gleevec working on c-kit (and work being done by Dr Wen Jen Hwu at MDA), prescribed it off-label for me. My tumors became stable within 30 days and have remained stable for another 2 1/2 years.
    
       Since that time there has been much more work and trials fo drugs targged at the C-kit mutations. I strongly recommend getting the oncoprotein stain test (The first test for c-kit – can be done by any local lab). If positive, a c-kit mutation test can be conducted by a specialized lab.
    
    Below is information about drugs that help when one has the c-kit oncoprotein overexprssion and the c-kit DNA mutations.
    
    http://mmdm.cancercommons.org/ml/index.php/C-KIT
    
    Activating c-KIT mutations have been implicated in a variety of cancers (Lennartsson 2005) starting with GIST (Gastrointestinal stromal tumors) and CML (Chronic Myelogenous Leukemia). Because of this, there are both approved drugs and drugs in clinical development that target c-KIT including Imatinib, Sunitib, Nilotinib and Dasatanib.
    
    In 2006, Boris Bastian's group conducted a systematic study evaluating the frequency of c-KIT aberrations in melanoma and found mutations and/or copy number increases in 39% of mucosal, 36% of acral and 28% of melanomas on chronically sun-damaged skins but not in melanomas on skin without chronic sun damage (Curtis 2006). Several additional studies have investigated frequency of c-KIT aberrations since and are summarized below. Also, 30% of melanoma with c-KIT mutations also show increased copy number/amplification of c-KIT.
    
    c-KIT aberrations in melanoma (Woodman 2010)
    
    Type of melanoma
    Copy number
    Mutations
    
    Acral
    24%
    
    Mucosal- All
    26%
    
    Mucosal- Head & neck
    
    12%
    
    Mucosal- Geritourinary
    
    27%
    
    Mucosal- Anorectal
    
    12%
    
    c-KIT is increasingly considered a leading therapeutic target for melanoma. So far, supporting data has primarily come from case reports and small studies (Hodi 2008, Lutzky 2008, Satzger 2010). However, both approved and new drugs are being testing in melanoma with c-KIT aberrations and results are awaited
    
    Drugs Targeting C-Kit
    
    Drug Class
    Company
    HasDevelopmentStatus
    Clinical Trial
    
    Dasatinib
    C-KIT inhibitors
    Bristol-Myers Squibb
    Approved for chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)
    NCT01092728
    NCT00436605
    NCT00597038
    NCT00792545
    
    Gleevec
    C-KIT inhibitors
    Novartis
    Approved for Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML), Kit (CD117)–positive gastrointestinal stromal tumors (GIST)
    NCT00424515
    NCT00470470
    NCT00667953
    NCT00881049
    NCT00421317
    NCT01046487
    
    Sutent
    C-KIT inhibitors
    Pfizer
    Approved for advanced kidney cancer and Gleevec-resistant GIST
    NCT00631618
    NCT00577382
    NCT00859326
    NCT01216657
    NCT01005472
    NCT00489944
    
    Tasigna
    C-KIT inhibitors
    Novartis
    Approved for drug-resistant Chronic Myeloid Leukemia (CML)
    NCT00788775
    NCT01168050
    NCT01028222
    NCT01099514
    
    Pathway
    c-KIT pathway
    
    Technology
    Targeted sequencing
    
    Vendors
    Arup, Fox Chase, Caris, Mayo Clinic, MPLN, TML, UCSF
    
    DrugClass
    c-KIT inhibitors
    
    Comments
    
    Relevant Subtypes: Subtype 2.1
    
    Relevant Trials:
    
    Trials
    Status
    Title
    
    NCT00421317
    Recruiting
    Imatinib in Adult Patients With Metastatic Ocular Melanoma
    
    NCT00424515
    Recruiting
    Imatinib in Patients With Mucosal or Acral/Lentiginous Melanoma
    
    NCT00436605
    Active but not recruiting
    Dasatinib in Treating Patients With Stage III Melanoma That Cannot Be Removed By Surgery or Stage IV Melanoma
    
    NCT00470470
    Recruiting
    Imatinib Mesylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery
    
    NCT00489944
    Recruiting
    Sunitinib, Tamoxifen, and Cisplatin in Treating Patients With High-Risk Ocular Melanoma
    
    NCT00577382
    Recruiting
    SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma
    
    NCT00597038
    Active, not recruiting
    A Phase I/II Study of Dasatinib and Dacarbazine
    
    NCT00631618
    Recruiting
    Clinical Trial of Sutent to Treat Metastatic Melanoma
    
    NCT00667953
    Active not recruiting
    Study of Temzolomide and Gleevec in Advanced Melanoma
    
    NCT00700882
    Suspended
    Dasatinib in Treating Patients With Locally Advanced or Metastatic Mucosal Melanoma, Acral Melanoma, or Solar Melanoma That Cannot Be Removed By Surgery
    
    NCT00788775
    Recruiting
    Nilotinib in TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral, or Chronically Sun Damaged Melanoma
    
    NCT00792545
    Recruiting
    Dasatinib and Bevacizumab in Treating Patients With Solid Tumors That Are Metastatic or Cannot be Removed by Surgery
    
    NCT00859326
    Recruiting
    Combination of Temozolomide and Sunitinib in Treatment of Patients With Metastatic and Unresectable Malignant Melanoma
    
    NCT00881049
    Completed
    Trial of Imatinib (Gleevec®) in Selected Patients With Metastatic Melanoma
    
    NCT01005472
    Active not recruiting
    Temozolomide and Sunitinib Malate in Treating Patients With Stage III or Stage IV Malignant Melanoma
    
    NCT01028222
    Recruiting
    A Study of AMNN107 Against Dacarbazine (DTIC) in the Treatment of Metastatic and/or Inoperable Melanoma Harboring a c-Kit Mutation (TEAM)
    
    NCT01046487
    Recruiting
    Imatinib Mesylate And Cyclophosphamide In Metronomic Administration: Dose Escalation Study Of Imatinib Mesylate (PALANGI3)
    
    NCT01092728
    Not yet recruiting
    Treatment With Dasatinib in Patients With Acral Lentiginous, Mucosal, or Chronic Sun-damaged Melanoma
    
    NCT01099514
    Recruiting
    Study of Nilotinib in Metastatic Melanoma With KIT Aberrations
    
    NCT01168050
    Recruiting
    Efficacy of Nilotinib in First or Second Line Treatment of Primary Melanomas Stage III Unresectable Melanomas.
    
    NCT01216657
    Recruiting
    Trial of Single Agent Sunitinib for Patients With Chemo-refractory Metastatic Melanoma
    
    **********************************************************
    
    Also look at;
    
    http://oncologystat.com/journals/journal_scans/KIT_as_a_Therapeutic_Targ…
    
    http://www.melanoma.org/comment/reply/26098/71256
    
    Even if one does not have the C-kit nor BRAF (they are mutually exlusive) One cannot ubequivalently state that "chemo doesn't touch melanoma." There are many chemo's that have made some melanoma patients NED or else slowed their disease (Most only in the 1-3% range). The problem is that we have not yet learned why they work on the few that they do work on.
    
       IL-2 and Ipi (Yervoy), Immunotherapy treatments (not considered chemo), have a record of helpiing around 20% of across the board melanoma stage IV patients. Again they don 't know exactly why, but these broad spectrum treatments can be effective for many. So far IL-2 has the highest long term "remission/cure" rate for about 5% of stage IV patients.
    
    *******************************************
    
    My email add is: [email protected]
  - December 29, 2013 at 2:59 pm
    
    Quote
    Cooper
    Participant
    
    Seems like a waste of work and money since IL2 doesn't work for 94% of patients. LIke to see the old drugs give way to the new ones that don't harm the body so much and you don't have to spend time in the Intensive Care Unit to get the drug. So if they do come up with a test it will still only benefit 5% of patients. Resources get wasted on old stuff because of the money interest to keep it alive.
- - December 29, 2013 at 1:27 am
  - Quote
  Joannezaras
  Participant
  Hi Jerry
  
  my mom has recently been diagnosed and had surgery for Mucusal Melonoma if the parasinus. We are just at the beginning of this journey. I was reading about your treatment and wondered if you knew if it was happening in Canada as well? We have our first appointment with the oncologist coming up and a post op meeting with the surgeon with radiation starting shortly. Where do we start with getting tested for the drug you are taking?