tarceva confusion

[magic]

Hi,

My friend is thinking about going on Tarceva.

Is this only available on private health?

Anyone know of good ways to combat the skin side effects?

Does it reduce the tumour in the lung, keep it stable, work on the metastasis or do everything? My research is a bit unclear!

Thanks

x

[TracyD]

I just recently started Tarceva and all I can tell you is what the doctors and my own research have told me. Tarceva can do all of those things, or possibly none of them. In a minority of people the tumor can shrivel up and die, in others the disease will not progress, and in others it will have no effect and the tumor will continue to grow. I do know that nonsmoking women have the best response to the drug overall, that is why I chose to try if first.

I am receiving Tarceva in a clinical trial as a first line therapy. My insurance will only pay for it as a second line, after a chemo treatment has failed. They will also pay for it if we find that it is working for me and I get out of the trial.

As for side effects, I don't know. I have been on it for six days and all I have to show is a mild, slightly itchy rash on my upper torso that I haven't treated with anything but a good moisturizer. I also have some small mouth sores, also not bothersome.

Hope this helps.

Tracy

[Jyoung20]

Hi Magic,

I have been on Tarceva now for almost a year and have been very fortunate in that it has kept my cancer at bay. This was a first line treatment and I began as soon as raidation and chemo were finished. In comparision to the chemo and radiation, the side effects for me have been minimal. Dry skin that I battle all of the time. Rashes on my arms and face sometimes.(they do go away). Very sensitive skin and very, very dry skin around my extremities. The skin on my fingers will just split open. I have also found that it takes longer to heal those areas.

I know this sounds like alot but these are only minor issues. I am just letting you know all of my side effects. People are affected differently as they are with most medicines. So, the side effects that I have may not be the same for someone else. I have found ways to deal with these side effects. Change in diet, fish oil, all-natural and/or organic skin products. So far, it has been very tolerable

Hope this helps!!

GOD BLESS!

Jamie

[karen335]

Drink LOT'S of water too...

[Bill]

Hi,

Does it reduce the tumour in the lung, keep it stable, work on the metastasis or do everything? My research is a bit unclear!

Thanks

x

M :

IMO, in a narrow group of well-defined responders, Tarceva can work exceptionally well. Most of the clinical literature indicates that improvement will hold for ~ 6 to 9 months. ( Here's an example article in which irreversible EGFR inhibitors are discussed ).

http://www.mgh.harvard.edu/news/release ... haber.html

My wife fit the responder criteria exceptionally well. While on monotherapy with Tarceva, she went from near death to very near NED over an ~ 8 to 9 month period. Then, all improvement suddenly vanished over the following ~ 3 months. One surprising fact of this reversal is that ~ 90% of her current, active tumors are in the same locations, that is same distribution pattern, as that before starting Tarceva. Tumor sites thought to be dead obviously weren't even though PET scans during peak improvement showed no abnormal activity at these locations. Even a malignant pleural effusion recently reformed which was identical in size and location to the one that she had just prior to starting Tarceva.

B

[kamataca]

Mom has been on Tarceva for a year now. She uses Aveno lotion to help with the dry skin. Her tumor hasn't shrunk, but it has not grown significantly in the past year.

She was originally given a life-expectancy of 12 months (those silly statistics), so we call that good! She has had no other treatment for the lung tumor (only radiation to her skull).

Kelly

[Shar]

Hi,

I have been on Tarceva for just over a year now and it has given me amazing results. Just incredible really!!

I must say the side effects I experience have been extreme. I just think that the drug is working and that is all that matters to me.

I have found the rash on my scalp to be the worst of all the side effects, I am on skin antibiotics every month now and that does seem to lessen the pain eventually.

Everybody is different of course, I am yet to find anybody out there who experiences what I do.

Just remember the results are worth it, so good luck!!!

Sharon

[gpawelski]

Increasingly, targeted oral-dose anti-cancer drugs like Tarceva (and Iressa) are found to treat cancers effectively, in those that it IS helping. These targeted cancer therapies will give doctors a better way to tailor cancer treatment. Treatments need to be 'individualized' based on the unique set of molecular targets produced by the patient's tumor, and these important treatment advances will require individualized assay-testing (molecular and cellular) which can improve patient survival.

Tarceva is one of those things that benefits a very few patients a whole lot, is neutral in most, and is bad (e.g. strokes) in a few. An analysis prepared by the FDA staff questioned the benefits of Tarceva because it found that the pill caused a significant increase in toxicity, including a sixfold rise in strokes. However, the thrust is to identify an on-patent therapy which is microscopically better in clinical trials of one-size-fits-all treatment.

Why do some lung cancers stop responding to Tarceva?

Tarceva is a "targeted" therapy, in that it halts the growth of certain cancers by zeroing in on a signaling molecule critical to the survival of those cancer cells. The drug is effective in about 10-15% of patients with non-small cell lung cancer. The drug works specifically in patients whose cancers contain mutations in a gene that encodes the epidermal growth factor receptor (EGFR). Lung cancer patients with these mutations are often people who have never smoked.

Although these targeted therapies are initially effective in this subset of patients, the drugs eventually stop working, and the tumors begin to grow again. This is called acquired or secondary resistance. This is different from primary resistance, which means that the drugs never work at all.

Initially, tumors have the kinds of mutations in the EGFR gene that were previously associated with responsiveness to these drugs. But, sometime tumors grow despite continued therapy because an additional mutation in the EGFR gene, strongly implies that the second mutation was the cause of drug resistance. Biochemical studies have shown that this second EGFR mutation, which was the same as before, could confer resistance to the EGFR mutants normally sensitive to these drugs.

It is especially interesting to note that the mutation is strictly analogous to a mutation that can make it tumor resistant. Non-small cell lung cancer makes up about 80 percent of all lung cancers. Mutations in a gene called KRAS, which encodes a signaling protein activated by EGFR, are found in 15 to 30 percent of these cancers. The presence of a mutated KRAS gene in a biopsy sample is associated with primary resistance to these drugs.

Tumor cells from patients in a study who developed secondary resistance to Tarceva after an initial response on therapy did not have mutations in KRAS. Rather, these tumor cells had new mutations in EGFR. This further indicates that secondary resistance is very different from primary resistance.

All the EGFR mutation or amplification studies can tell us is whether or not the cells are potentially susceptible to this mechanism of attack. They don't tell you if Tarceva is better or worse than some other drug which may target this. There are differences. The drug has to get inside the cells in order to target anything.

EGF-targeted drugs like Tarceva are poorly-predicted by measuring the ostansible target EGFR, but can be well-predicted by measuring the effect of the drug on the "function" of live cells. An EGFRx targeted therapy profile includes analysis of the following targeted drugs: Tarceva, Iressa, Nexavar, and Sutent.

Literature Citation:

PLoS Medicine, February 22, 2005

[Bill]

Tarceva is one of those things that benefits a very few patients a whole lot, is neutral in most, and is bad (e.g. strokes) in a few. An analysis prepared by the FDA staff questioned the benefits of Tarceva because it found that the pill caused a significant increase in toxicity, including a sixfold rise in strokes.

G :

Interesting. Could you please post the link ? The hemodynamic risk that you mention sounds very similar to that associated with Avastin. I was unaware that there is such a high risk of stroke associated with Tarceva.

Thanks.

B

[gpawelski]

There are specialists at the FDA who begin to analyze data provided in an application. (One of my wife's sons was an examiner with the Patent Office and we spent an exhaustive day learning about their process.)

In this in-depth analysis, the FDA staffers go through the complete case histories of patients in each of the Phased clinical trials for a drug. At the end of the process, these staffers create briefing documents. They advocate the pros and cons on the safety and efficacy of a product.

These briefing documents are then sent to FDA managment. The management has the option of taking action on their own or forwarding the briefing documents to an advisory committee.

The advisory committee adds a series of questions to the briefing documents. The panel votes on the questions. The FDA staffers make presentations of the data. Then the panel debates the pros and cons of the drug. At the end of lively debate, the panel members vote on the questions. It's a vote, and majority rules. Even if the minority had objections because of some adversed side effects.

The FDA Advisory Committee panel votes are not binding on the FDA. Once the panel votes, FDA managment reviews their input and makes the final decision on the drug (good, bad, or indifferent). And not everything makes it to the final copy!