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first line treatment and questions- Dr. Joe can you help??


JonathanS

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Hi everyone,

For those of you who do not know me, my name is Jonathan and I am into oncology research, and currently in my 4th year of nursing school. My area will be oncology research nursing hopfully here at the University of Chicago Hospitals. Anyway, as I research for better treatments I must wonder a few things about sclc...

1.) What is the best first line therapy?

A.) cisplatin/carboplatin with etoposide

B.) cisplatin/carboplatin with CPT-11

Studies have shown a benefit in survival and long trem remissions with choice "B" in extensive staged patients, however, shouldn't that also carry over to limited staged automatically?? I mean if regimen "B" is better for late staged disease, wouldn't it automatically be better for early staged patients as well?

2.) Are there any studies looking at combining all three agents in first line therapy (cisplatin/carboplatin with etoposide and CPT-11)??

3.) Drug resistance is the biggest problem with sclc, so why not alternate drugs before it is necessary. Like this example...

cycle 1: give cisplatin with cpt-11

cycle 2: give cisplatin with etoposide

cycle 3: give taxol with cisplatin

this way the cancer cannot build up an immunity to the drugs as it being hit roughly at the same time with different agents. It will nto know what hit it or what to expect next in other words. Has there ever been a study like this? Is there a rationale here?

4.) Does gemzar play a role in sclc, and if so what role?

5.) After a pt goes into remission, why not resect the area of the lung the tumor began in --either the lobe or the wegde resection to eliminate the source of the disease. I know that surgery has been reseached way back, but not recentley with sclc, and we really do have better drugs and techniques today-so why not explore surgery again -either before or after remission??

Thanks for any answers you can give me....I know these are had questions, and I am honored to have an oncologist such as yourself help me answer them....Thnaks Dr. Joe we need you here!!!

Jonathan

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Wow, lots of good questions Jonathon. I'll try to go one by one:

1) If you are Japanese, then CPT-11/Cisplatin is the best treatment. If you are not Japanese, then no one knows for sure. The study showing superior outcomes with CPT-11/Cisplatin was kind of a messy study, I was at ASCO when the authors presented it and they were heavily critisized for the study design. I think the results are real, however. There are two randomized trials that I know of that are currently trying to answer this question in the U.S. Until they are completed, I don't think it is wrong to use either treatment. CPT-11/Cisplatin is more intensive so I think you definitely have to use good clinical judgement when deciding who to give it to.

In terms of applying it to limited stage disease, that is a leap of faith that I would be very cautious about making. The most important factor with limited stage disease is incorporating the radiation and the chemotherapy. There is very limited data with CPT-11/Cisplatin and concurrent radiation and I think that it should only be done as part of a clinical trial. Oncology history is littered with chemo regimens that worked great for advanced disease and ended up being worse for limited disease (CPT-11 in colon cancer is a good example, study had to be stopped because of excessive deaths with CPT-11 compared to the "old" treatment).

2) I'm not aware of using those 3 drugs together. Certainly "triplets" have been tried and again are a good cautionary tale. The "PET" regimen (cisplatin, etoposide, taxol) was popularized by MD Anderson and in early studies was very promising. Taxol is a very active drug in small cell and adding it to the best combination made sense. But randomized trials showed that it caused more toxic deaths with no significant difference in survival:

http://www.asco.org/ac/1,1003,_12-00263 ... 169,00.asp

3) Alternating regimens to overcome resistance is a very attractive idea but unfortunately has been largely ineffective. Here are a couple older trials alternating platinum/etoposide and CAV:

http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract

This one showed a very small advantage in a Japanese population:

http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract

This study looked at alternating platin/etoposide and topotecan (more "modern" chemo) and does not suggest a significant advantage:

http://www.ncbi.nlm.nih.gov/entrez/quer ... s=12733149

4) Gemcitabine alone is not very active in small cell lung cancer although it is occasionally used. I would consider it 4th or 5th line after platin/vp-16, cpt-11, topotecan, taxol.

5) Resection has been looked at and again has not impacted survival, probably because small cell tends to recur elsewhere in the body.

http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract

Hope that helps, good luck with finishing school!

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Dr. Joe,

Dave is currently getting cisplatin and cpt-11 WHILE getting 30 days of radiation to this bonkitis tumor (forehead sinus and surrounding bone tumor).

Why is that not a good idea unless in a clinical trial? He's not in a clinical trial.

His oncologist - who is very highly respected . . . . told us it was in clinical trial, this regimen, but is giving it to Dave outside of the trial. Dave is doing pretty good on it, the cisplatin really kicks his butt, the radiation gave him a little bit of a burn, but the tumor appears to the naked eye to be shrinking and on Monday when he goes in for chemo I suppose we'll get the results of the CT scan he had this week.

Karen C.

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Giving it with radiation in the bone is much less risky. Giving highly sensitizing chemotherapy while radiating the lung can increase the risk of radiation pneumonitis, a potentially serious complication. My point is, until we have evidence that this combination is better with concurrent radiation for limited stage disease, I really don't think it should be considered the standard of care. Not that it can't be done or hasn't been done, I have used it myself. But cisplatin/etoposide in my opinion should still be considered the standard with radiation for limited stage. Its hard waiting for results of clinical trials but still the right thing to do.

Your situation is different and I have no problem using CPT-11 or taxol with radiation with treatment in other recurrent sites.

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Dr. Joe,

I have a question for you regarding the point you brought up being Japanese. My husband just finished his 4th and last round of chemo (cisplatin/etoposide) just today. He is 1/2 Japanese. His mother died in "92 of sclc as well and received the same treatment. She was full Japanese. Would bringing up his heritate to his doctor, make a difference?? If by chance he has to go through more chemo, could this change the course?

Thank you very much,

Lori

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Lori,

I think Dr. Joe made the "Japanese" comment because those studies and clinical trials were done in Japan with a Japanese population. I don't think he meant it as a racial marker in general.

There is not an accurate accounting of how these studies would effect westerners, our lifestyles, our dietary habits, etc... no one knows for sure (and that includes all races in the US)

hope that helps.

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Katie is right, my point was that the pivotal study with CPT-11/Cisplatin was done in a Japanese patient population. There is definitely something different about the Japanese population however. If you look at the Iressa data for example, the response in Japan was much different (better) than in the U.S. or Europe. Not sure if this is due to genetics, diet, environment or what.

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He, Dr. Joe, got your point about the treatment for limited stage - still in the lung - you know, both the oncologist and the radiation oncologist talked about the chemo being highly sensitizing and that's why they were reluctant to do radiation concurrent with the chemo at the beginning, but when the bonikitis bump appeared to be growing instead of shrinking after the first round of chemo they decided to go ahead and do the radiation at the same time. I can see how that would be dangerous with chest radiation. seems to me that alot of folks on this board who have passed away, the younger patients, that is, was from radiation pneumonia or otherwise chronic fluid in the lungs. dave has been fortunate to not have had that problem.

his oncologist and radiation oncologist both said they'd never seen lung cancer go to a sinus cavity . . . but both said as well, have always told us this, that cancer can and will go anywhere. Dave has sure proven that.

Karen

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Dr. Joe,

Thank you very much for replying so well to my questions and for giving me all those intersting links. It looks like there is some rationale for maybe alterbating cpt-11 and cisplatin with cisplatin and etoposide in the future, seeing as topotecan alternated with it showed a small, but real advantage. I have 1 more question if you don't mind...

If someone is resistant to topotecan, is CPT-11 still an option??? Iknow they are in the same family so i thought I'd ask.

Thanks again!!! We need you here, and frankly have needed you here for some time...You are one of the most concerned, caring and compassionate oncoogists I have ever spoken to...

Sincerely,

Jonathan

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