Ulceration? Why is this an important factor?

I'm sorry you have been diagnosed with melanoma, but you've come to the right place.  I would be lost without the support and wealth of information from this great group!

I was also diagnosed earlier this year with a very deep primary, nodular melanoma (22mm) with ulceration.  I also had macro mets to one lymph node and it's now in my lungs.  My mitosis was less than 1, but since I had spread to a lymph node, my onc. didn't seem to think it mattered.  I think mitosis is more important in thin melanomas, but I could be wrong.

I was faced with the same problem as you when I was diagnosed – I had NED after surgery, so in essence, the melanoma was gone. I chose to get myself into a clinical trial with a placebo arm versus ipillumumab. I wanted to do something that was newer and showing more benefit over Interferon – especially considering my melanoma was deep and possibly already in my bloodstream. Everyone is different – it could take months or years to come back – nobody knows.

I wish you the best of luck and hope that you have many years of NED!

Lisa

I'm sorry you have been diagnosed with melanoma, but you've come to the right place.  I would be lost without the support and wealth of information from this great group!

I was also diagnosed earlier this year with a very deep primary, nodular melanoma (22mm) with ulceration.  I also had macro mets to one lymph node and it's now in my lungs.  My mitosis was less than 1, but since I had spread to a lymph node, my onc. didn't seem to think it mattered.  I think mitosis is more important in thin melanomas, but I could be wrong.

I was faced with the same problem as you when I was diagnosed – I had NED after surgery, so in essence, the melanoma was gone. I chose to get myself into a clinical trial with a placebo arm versus ipillumumab. I wanted to do something that was newer and showing more benefit over Interferon – especially considering my melanoma was deep and possibly already in my bloodstream. Everyone is different – it could take months or years to come back – nobody knows.

I wish you the best of luck and hope that you have many years of NED!

Lisa

Denise, do not let this information be the sole basis your decision, as the numbers are not impressive for interferon. (then again, what is when it comes to melanoma?) This information merely states that since your melanoma is ulcerated, you may have a better chance in a delay of recurrence than if it was not ulcerated.

Interferon is not very effective in the majority of patients. IFN treatment may delay the time to a potential recurrence, but is now known that the overall chance of survival time is not improved.

You may wish to research further the one month high dose vs. the 11 month low dose, and the potential side effects as well, such as depression.

Good luck,

Michael

Sorry, I should have been more clear. Sometimes it is lost in typing translation.

Also, please be aware that I am not trying to push interferon on you in any way, but just to help inform you instead. Whatever you do, the decision is yours to make.

What I meant was to read up on the one month studies vs. the 11 months after. Some studies show that the one month high dose may be as effective as the 11 months low dose.

Here is something you may wish to read as well:

http://www.melanomacenter.org/treatment/lowdoseinterferon.html

Similar info here:

http://www.aimatmelanoma.org/aim-for-answers/treatment-of-melanoma/immunotherapy/interferons.html

Michael

Oh, and not all trails have a placebo:

http://clinicaltrials.gov/ct2/info/understand

From WIKI:

http://en.wikipedia.org/wiki/Clinical_trial

Phase I

Phase I trials are the first stage of testing in human subjects. Normally, a small (20-100) group of healthy volunteers will be selected. This phase includes trials designed to assess the safety (pharmacovigilance), tolerability, pharmacokinetics, and pharmacodynamics of a drug. These trials are often conducted in an inpatient clinic, where the subject can be observed by full-time staff. The subject who receives the drug is usually observed until several half-lives of the drug have passed. Phase I trials also normally include dose-ranging, also called dose escalation, studies so that the appropriate dose for therapeutic use can be found. The tested range of doses will usually be a fraction of the dose that causes harm in animal testing. Phase I trials most often include healthy volunteers. However, there are some circumstances when real patients are used, such as patients who have terminal cancer or HIV and lack other treatment options. "The reason for conducting the trial is to discover the point at which a compound is too poisonous to administer."^[21] Volunteers are paid an inconvenience fee for their time spent in the volunteer centre. Pay ranges from a small amount of money for a short period of residence, to a larger amount of up to approx $6000 depending on length of participation.

There are different kinds of Phase I trial:

Single Ascending Dose studies are those in which small groups of subjects are given a single dose of the drug while they are observed and tested for a period of time. If they do not exhibit any adverse side effects, and the pharmacokinetic data is roughly in line with predicted safe values, the dose is escalated, and a new group of subjects is then given a higher dose. This is continued until pre-calculated pharmacokinetic safety levels are reached, or intolerable side effects start showing up (at which point the drug is said to have reached the Maximum tolerated dose (MTD)).

SAD

Multiple Ascending Dose studies are conducted to better understand the pharmacokinetics & pharmacodynamics of multiple doses of the drug. In these studies, a group of patients receives multiple low doses of the drug, while samples (of blood, and other fluids) are collected at various time points and analyzed to acquire information on how the drug is processed within the body. The dose is subsequently escalated for further groups, up to a predetermined level.

MAD

A short trial designed to investigate any differences in absorption of the drug by the body, caused by eating before the drug is given. These studies are usually run as a crossover study, with volunteers being given two identical doses of the drug while fasted, and after being fed.

Food effect

Phase II

Once the initial safety of the study drug has been confirmed in Phase I trials, Phase II trials are performed on larger groups (20-300) and are designed to assess how well the drug works, as well as to continue Phase I safety assessments in a larger group of volunteers and patients. When the development process for a new drug fails, this usually occurs during Phase II trials when the drug is discovered not to work as planned, or to have toxic effects.

Phase II studies are sometimes divided into Phase IIA and Phase IIB.

• Phase IIA is specifically designed to assess dosing requirements (how much drug should be given).
• Phase IIB is specifically designed to study efficacy (how well the drug works at the prescribed dose(s)).

Some trials combine Phase I and Phase II, and test both efficacy and toxicity.

Some Phase II trials are designed as case series, demonstrating a drug's safety and activity in a selected group of patients. Other Phase II trials are designed as randomized clinical trials, where some patients receive the drug/device and others receive placebo/standard treatment. Randomized Phase II trials have far fewer patients than randomized Phase III trials.

Trial design

Phase III

Phase III studies are randomized controlled multicenter trials on large patient groups (300–3,000 or more depending upon the disease/medical condition studied) and are aimed at being the definitive assessment of how effective the drug is, in comparison with current 'gold standard' treatment. Because of their size and comparatively long duration, Phase III trials are the most expensive, time-consuming and difficult trials to design and run, especially in therapies for chronic medical conditions.

It is common practice that certain Phase III trials will continue while the regulatory submission is pending at the appropriate regulatory agency. This allows patients to continue to receive possibly lifesaving drugs until the drug can be obtained by purchase. Other reasons for performing trials at this stage include attempts by the sponsor at "label expansion" (to show the drug works for additional types of patients/diseases beyond the original use for which the drug was approved for marketing), to obtain additional safety data, or to support marketing claims for the drug. Studies in this phase are by some companies categorised as "Phase IIIB studies."^[22][23]

While not required in all cases, it is typically expected that there be at least two successful Phase III trials, demonstrating a drug's safety and efficacy, in order to obtain approval from the appropriate regulatory agencies such as FDA (USA), or the EMA (European Union), for example.

Once a drug has proved satisfactory after Phase III trials, the trial results are usually combined into a large document containing a comprehensive description of the methods and results of human and animal studies, manufacturing procedures, formulation details, and shelf life. This collection of information makes up the "regulatory submission" that is provided for review to the appropriate regulatory authorities^[3] in different countries. They will review the submission, and, it is hoped, give the sponsor approval to market the drug.

Most drugs undergoing Phase III clinical trials can be marketed under FDA norms with proper recommendations and guidelines, but in case of any adverse effects being reported anywhere, the drugs need to be recalled immediately from the market. While most pharmaceutical companies refrain from this practice, it is not abnormal to see many drugs undergoing Phase III clinical trials in the market.^[24]

Phase IV

Phase IV trial is also known as Post-Marketing Surveillance Trial. Phase IV trials involve the safety surveillance (pharmacovigilance) and ongoing technical support of a drug after it receives permission to be sold. Phase IV studies may be required by regulatory authorities or may be undertaken by the sponsoring company for competitive (finding a new market for the drug) or other reasons (for example, the drug may not have been tested for interactions with other drugs, or on certain population groups such as pregnant women, who are unlikely to subject themselves to trials). The safety surveillance is designed to detect any rare or long-term adverse effects over a much larger patient population and longer time period than was possible during the Phase I-III clinical trials. Harmful effects discovered by Phase IV trials may result in a drug being no longer sold, or restricted to certain uses: recent examples involve cerivastatin (brand names Baycol and Lipobay), troglitazone (Rezulin) and rofecoxib (Vioxx).

Phase V

Phase V is a growing term used in the literature of translational research to refer to comparative effectiveness research and community-based research; it is used to signify the integration of a new clinical treatment into widespread public health practice. [1]

Oh, and not all trails have a placebo:

http://clinicaltrials.gov/ct2/info/understand

From WIKI:

http://en.wikipedia.org/wiki/Clinical_trial

Phase I

Phase I trials are the first stage of testing in human subjects. Normally, a small (20-100) group of healthy volunteers will be selected. This phase includes trials designed to assess the safety (pharmacovigilance), tolerability, pharmacokinetics, and pharmacodynamics of a drug. These trials are often conducted in an inpatient clinic, where the subject can be observed by full-time staff. The subject who receives the drug is usually observed until several half-lives of the drug have passed. Phase I trials also normally include dose-ranging, also called dose escalation, studies so that the appropriate dose for therapeutic use can be found. The tested range of doses will usually be a fraction of the dose that causes harm in animal testing. Phase I trials most often include healthy volunteers. However, there are some circumstances when real patients are used, such as patients who have terminal cancer or HIV and lack other treatment options. "The reason for conducting the trial is to discover the point at which a compound is too poisonous to administer."^[21] Volunteers are paid an inconvenience fee for their time spent in the volunteer centre. Pay ranges from a small amount of money for a short period of residence, to a larger amount of up to approx $6000 depending on length of participation.

There are different kinds of Phase I trial:

Single Ascending Dose studies are those in which small groups of subjects are given a single dose of the drug while they are observed and tested for a period of time. If they do not exhibit any adverse side effects, and the pharmacokinetic data is roughly in line with predicted safe values, the dose is escalated, and a new group of subjects is then given a higher dose. This is continued until pre-calculated pharmacokinetic safety levels are reached, or intolerable side effects start showing up (at which point the drug is said to have reached the Maximum tolerated dose (MTD)).

SAD

Multiple Ascending Dose studies are conducted to better understand the pharmacokinetics & pharmacodynamics of multiple doses of the drug. In these studies, a group of patients receives multiple low doses of the drug, while samples (of blood, and other fluids) are collected at various time points and analyzed to acquire information on how the drug is processed within the body. The dose is subsequently escalated for further groups, up to a predetermined level.

MAD

A short trial designed to investigate any differences in absorption of the drug by the body, caused by eating before the drug is given. These studies are usually run as a crossover study, with volunteers being given two identical doses of the drug while fasted, and after being fed.

Food effect

Phase II

Once the initial safety of the study drug has been confirmed in Phase I trials, Phase II trials are performed on larger groups (20-300) and are designed to assess how well the drug works, as well as to continue Phase I safety assessments in a larger group of volunteers and patients. When the development process for a new drug fails, this usually occurs during Phase II trials when the drug is discovered not to work as planned, or to have toxic effects.

Phase II studies are sometimes divided into Phase IIA and Phase IIB.

• Phase IIA is specifically designed to assess dosing requirements (how much drug should be given).
• Phase IIB is specifically designed to study efficacy (how well the drug works at the prescribed dose(s)).

Some trials combine Phase I and Phase II, and test both efficacy and toxicity.

Some Phase II trials are designed as case series, demonstrating a drug's safety and activity in a selected group of patients. Other Phase II trials are designed as randomized clinical trials, where some patients receive the drug/device and others receive placebo/standard treatment. Randomized Phase II trials have far fewer patients than randomized Phase III trials.

Trial design

Phase III

Phase III studies are randomized controlled multicenter trials on large patient groups (300–3,000 or more depending upon the disease/medical condition studied) and are aimed at being the definitive assessment of how effective the drug is, in comparison with current 'gold standard' treatment. Because of their size and comparatively long duration, Phase III trials are the most expensive, time-consuming and difficult trials to design and run, especially in therapies for chronic medical conditions.

It is common practice that certain Phase III trials will continue while the regulatory submission is pending at the appropriate regulatory agency. This allows patients to continue to receive possibly lifesaving drugs until the drug can be obtained by purchase. Other reasons for performing trials at this stage include attempts by the sponsor at "label expansion" (to show the drug works for additional types of patients/diseases beyond the original use for which the drug was approved for marketing), to obtain additional safety data, or to support marketing claims for the drug. Studies in this phase are by some companies categorised as "Phase IIIB studies."^[22][23]

While not required in all cases, it is typically expected that there be at least two successful Phase III trials, demonstrating a drug's safety and efficacy, in order to obtain approval from the appropriate regulatory agencies such as FDA (USA), or the EMA (European Union), for example.

Once a drug has proved satisfactory after Phase III trials, the trial results are usually combined into a large document containing a comprehensive description of the methods and results of human and animal studies, manufacturing procedures, formulation details, and shelf life. This collection of information makes up the "regulatory submission" that is provided for review to the appropriate regulatory authorities^[3] in different countries. They will review the submission, and, it is hoped, give the sponsor approval to market the drug.

Most drugs undergoing Phase III clinical trials can be marketed under FDA norms with proper recommendations and guidelines, but in case of any adverse effects being reported anywhere, the drugs need to be recalled immediately from the market. While most pharmaceutical companies refrain from this practice, it is not abnormal to see many drugs undergoing Phase III clinical trials in the market.^[24]

Phase IV

Phase IV trial is also known as Post-Marketing Surveillance Trial. Phase IV trials involve the safety surveillance (pharmacovigilance) and ongoing technical support of a drug after it receives permission to be sold. Phase IV studies may be required by regulatory authorities or may be undertaken by the sponsoring company for competitive (finding a new market for the drug) or other reasons (for example, the drug may not have been tested for interactions with other drugs, or on certain population groups such as pregnant women, who are unlikely to subject themselves to trials). The safety surveillance is designed to detect any rare or long-term adverse effects over a much larger patient population and longer time period than was possible during the Phase I-III clinical trials. Harmful effects discovered by Phase IV trials may result in a drug being no longer sold, or restricted to certain uses: recent examples involve cerivastatin (brand names Baycol and Lipobay), troglitazone (Rezulin) and rofecoxib (Vioxx).

Phase V

Phase V is a growing term used in the literature of translational research to refer to comparative effectiveness research and community-based research; it is used to signify the integration of a new clinical treatment into widespread public health practice. [1]

Sorry, I should have been more clear. Sometimes it is lost in typing translation.

Also, please be aware that I am not trying to push interferon on you in any way, but just to help inform you instead. Whatever you do, the decision is yours to make.

What I meant was to read up on the one month studies vs. the 11 months after. Some studies show that the one month high dose may be as effective as the 11 months low dose.

Here is something you may wish to read as well:

http://www.melanomacenter.org/treatment/lowdoseinterferon.html

Similar info here:

http://www.aimatmelanoma.org/aim-for-answers/treatment-of-melanoma/immunotherapy/interferons.html

Michael

Denise, do not let this information be the sole basis your decision, as the numbers are not impressive for interferon. (then again, what is when it comes to melanoma?) This information merely states that since your melanoma is ulcerated, you may have a better chance in a delay of recurrence than if it was not ulcerated.

Interferon is not very effective in the majority of patients. IFN treatment may delay the time to a potential recurrence, but is now known that the overall chance of survival time is not improved.

You may wish to research further the one month high dose vs. the 11 month low dose, and the potential side effects as well, such as depression.

Good luck,

Michael

I agree with Linda.  Even one cell in the lymph nodes says that melanoma has traveled away from the original site through the lymph channels.  I'm not sure how your doctor can say you aren't stage III.  You'll find an easier time looking at clinical trials when you do it at stage III also. 

Stage IIIB: T4bN1aM0: The melanoma can be of any thickness and is ulcerated. It has spread to 1 to 3 lymph nodes near the affected skin area, but the nodes are not enlarged and the melanoma is found only when they are viewed under the microscope. There is no distant spread.

I do have another link I ran across that discusses a total lymph node dissection in people with minimal metastasis to the sentinal node.  It seems to apply to your minimal mets in the sentinel node.  http://www.gmmm.com.ve/lectura/00000658-200906000-00021.pdf

I know another warrior from Reno area traveled to CA to do treatment.  Are there any melanoma specialists in Reno?  I know Las Vegas has Dr. Samlowski (previously from Utah where I live), but not sure about Reno.

Good luck in your treatment research!

Janner

I agree with Linda.  Even one cell in the lymph nodes says that melanoma has traveled away from the original site through the lymph channels.  I'm not sure how your doctor can say you aren't stage III.  You'll find an easier time looking at clinical trials when you do it at stage III also. 

Stage IIIB: T4bN1aM0: The melanoma can be of any thickness and is ulcerated. It has spread to 1 to 3 lymph nodes near the affected skin area, but the nodes are not enlarged and the melanoma is found only when they are viewed under the microscope. There is no distant spread.

I do have another link I ran across that discusses a total lymph node dissection in people with minimal metastasis to the sentinal node.  It seems to apply to your minimal mets in the sentinel node.  http://www.gmmm.com.ve/lectura/00000658-200906000-00021.pdf

I know another warrior from Reno area traveled to CA to do treatment.  Are there any melanoma specialists in Reno?  I know Las Vegas has Dr. Samlowski (previously from Utah where I live), but not sure about Reno.

Good luck in your treatment research!

Janner

I have been to both….a really good oncologist….and then an oncologist who specialized in the treatment of melanoma.  Trust me no matter how much I liked the first guy it was such a world of difference.  RUN!  It is great that your doc wants to take your case to a tumor board and get more opinions but unless they are docs who speicailize in melanoma you are no better off.  Listen, I have been in your shoes….they did find "something" in my lymph node and it took a TON of specialist across the country to figure out what it was.  It was 2 cells…just 2, and even if it had been just one cell it was going to be a stage III.  Yes, just one teny-tiny microscopic cell.  Luckily mine ended up just being mole cells.  BUT anything that is positive for melanoma in your lymph node moves your staging.  Maybe it is not that way with other cancers-I really have no clue. 

I love your additude about things and getting the bottom of the best treatment options for your case is the best thing.  People on this board know more about diagnoising melanoma then my orginal doctor who removed my mole did.  Listen to them, they are an amazaing vast of knowledge, hope, and friendship.

Shoot one more thing to add….it is the pathologist who looks at the slides that really sees what is going on normally the guy that you in the office doesn't even ever look under the microscope to see the results.  I found it very important to get a second opinion on the pathology of it, or even better a pathologist who is really a Histopathologist.  I have 4 different lab reports and when my slides were sent to a David E Elder of the Univ of Penn.  the report was more detailed and ended up being triple the length of the other ones.  Amazing difference.  The original Pathologist who checked out the slides couldn't even make out what was in the lymph node…..

Shoot one more thing to add….it is the pathologist who looks at the slides that really sees what is going on normally the guy that you in the office doesn't even ever look under the microscope to see the results.  I found it very important to get a second opinion on the pathology of it, or even better a pathologist who is really a Histopathologist.  I have 4 different lab reports and when my slides were sent to a David E Elder of the Univ of Penn.  the report was more detailed and ended up being triple the length of the other ones.  Amazing difference.  The original Pathologist who checked out the slides couldn't even make out what was in the lymph node…..

I have been to both….a really good oncologist….and then an oncologist who specialized in the treatment of melanoma.  Trust me no matter how much I liked the first guy it was such a world of difference.  RUN!  It is great that your doc wants to take your case to a tumor board and get more opinions but unless they are docs who speicailize in melanoma you are no better off.  Listen, I have been in your shoes….they did find "something" in my lymph node and it took a TON of specialist across the country to figure out what it was.  It was 2 cells…just 2, and even if it had been just one cell it was going to be a stage III.  Yes, just one teny-tiny microscopic cell.  Luckily mine ended up just being mole cells.  BUT anything that is positive for melanoma in your lymph node moves your staging.  Maybe it is not that way with other cancers-I really have no clue. 

I love your additude about things and getting the bottom of the best treatment options for your case is the best thing.  People on this board know more about diagnoising melanoma then my orginal doctor who removed my mole did.  Listen to them, they are an amazaing vast of knowledge, hope, and friendship.

I did Interferon for two days in April of 2010.

They put a "picc" in my arm and taped it into place. This is like a more permanent IV.  The picc is like an IV needle but has a foot or so of very narrow tubing that is threaded into your vein and stops very near your heart. This means you don't have to stick your veins every day and also the interferon ends up close to your heart.

I lasted two days. The first day I developed a headache after the interferon injection. The second day I got the chills, fever, and crying spells. By the morning of the day of my third injection, I was a basket case. I almost ran into the clinic crying and repeating "I can't do this, I can't do this". First the social worker and nurse spoke with me and tried to calm me down. Then the onc came.  My onc said she would not allow me to continue the interferon. 

Now I am normally a pretty tough person (8 surgeries in my life) but this was out of control. I now realize it was a psychotic experience.

In the first place my onc said she didn't think the interferon would do much, certainly not affect my survival rate. She said I might try it if I want.

I don't recommend Interferon. Some do it and are in remission for years. Some do it and get a recurrence soon after. There is simply no way of knowing if it works. Who knows if those in remission for years would have been in remission without interferon? Who knows if those with recurrences would have had recurrences even if they did Interferon. No one knows.

Nicki, Stage 3b

I did Interferon for two days in April of 2010.

They put a "picc" in my arm and taped it into place. This is like a more permanent IV.  The picc is like an IV needle but has a foot or so of very narrow tubing that is threaded into your vein and stops very near your heart. This means you don't have to stick your veins every day and also the interferon ends up close to your heart.

I lasted two days. The first day I developed a headache after the interferon injection. The second day I got the chills, fever, and crying spells. By the morning of the day of my third injection, I was a basket case. I almost ran into the clinic crying and repeating "I can't do this, I can't do this". First the social worker and nurse spoke with me and tried to calm me down. Then the onc came.  My onc said she would not allow me to continue the interferon. 

Now I am normally a pretty tough person (8 surgeries in my life) but this was out of control. I now realize it was a psychotic experience.

In the first place my onc said she didn't think the interferon would do much, certainly not affect my survival rate. She said I might try it if I want.

I don't recommend Interferon. Some do it and are in remission for years. Some do it and get a recurrence soon after. There is simply no way of knowing if it works. Who knows if those in remission for years would have been in remission without interferon? Who knows if those with recurrences would have had recurrences even if they did Interferon. No one knows.

Nicki, Stage 3b