Has anyone tried Xeloda?

[KC]

Has anyone taken Xeloda for their lung cancer? I just spoke with someone at Roche Labs and they said there is no longer a restriction on diagnosis code, meaning that if your insurance covers it they will no matter what type of cancer you have. It was originally intended for Breast and Colorectal Cancer. Just wondering if anyone has already taken it and your experience. Thank you in advance.

[john]

Xeloda is also called capecitabine. I doubt too many people have tried this since it is like 5-FU (used for colorectal and breast cancer).

In their study, Han and colleagues[9] found that the combination of docetaxel and capecitabine showed antitumor activity in chemotherapy-naive patients with advanced NSCLC, although it was frequently associated with moderate-to-severe nonhematologic toxicities. Capecitabine is an oral fluoropyrimidine carbamate that generates 5-fluorouracil preferentially in tumor tissue by the action of thymidine phosphorylase. In vivo synergistic activity depends upon docetaxel-induced upregulation of thymidine phosphorylase. In a phase 2 study, 39 patients received twice-daily 1000 mg/m2 capecitabine on days 1-14 plus intravenous docetaxel 36 mg/m2 on days 1 and 8, once every 21 days, for a maximum of 6 cycles. In 36 eligible patients, 19 (53%) partially responded. Median duration of response was 6.2 months. During a median follow-up of 7.2 months, 9 patients died (2 deaths were treatment-related). The most common grade 3-4 hematologic toxicity was neutropenia (13%).

[john]

Since your dad has BAC. Do a search and you will find that EGFR inhibitors work well.

1) There may be a study on a combination of Heceptin/Tarceva in a clinical trial.

2) There is also GVAX which I think works better on BAC.

3) There is also a clinical study on a drug called CI-1033. This inhibits the four epidermal growth factors. (HER1, HER2, HER3, and HER4).

http://www.clinicaltrials.gov/ct/show/N ... 95?order=8

Tarceva is also called OSI-774 and Erlotinib

http://www.clinicaltrials.gov/ct/search ... 74%2Cnsclc

http://www.clinicaltrials.gov/ct/show/N ... 30?order=1

[john]

One thing to consider. Are they absolutely sure that the lung is the primary. If there are multiple tumors in the lungs, "sometimes" that signals they are mets vs being the primary.

This is what a friend of my wife said. (She is a pulmonologist) and her husband is one (specializing in lung cancer at Georgetown).

They can do different stainings to rule out mets.

[KC]

Thanks for all the information John. The problem with my father's case is that he has tried almost all of the chemotherapy regimines available and he has tried Iressa, so his trying Iressa pretty much excludes him from another clinical trial with a similar drug like Tarceva. We can only hope for approval so we can get it through prescription. That is why I was looking into the Xeloda. We looked into the GVAX trial months ago and met with a dr. about it. They wanted to get the tumor from my father lung but my father did not want to have a major surgery to harvest the tumor, and I didn't push him. I hear now that they are not doing major surgeries any longer for the GVAX trial. Unforutnately, my father's pleural effusion was too small to get the cells from there and there were no lymph nodes to take it from either. My dad was diagnosed back in Dec. 2001. There were I think 3 tumors in one lung and 2 in the other. I asked the onc. at Sloan Kettering who we went to for a second opinion if he thought they were mets or if they all popped up at the same time and he believe that they metastasized from one lung to the other. I still believe to this day that they all popped up at the same time, but I don't really believe it matters, all I know is I begged for surgery and couldn't find anyone to do it. I also looked into RFA at the time, but my father's tumors were all too small and they wouldn't do that either. I want him to try Iressa again, he only tried it for 10 weeks back in May 2002. He had slight progression and the onc. took him off right away. I still think he should have continued for a while longer, but it was under expanded access at the time and the protocol was too remove, or so that is what I am told. I am asking my father to try it again, but he gets annoyed with me and says it didn't work the last time. I told him it is better than doing nothing and he kind of agrees. We still don't know the plan, CT scans were today. Dad is in the hospital trying to keep the pain from the radiation to the bone mets under control. He can only receive the pain meds through IV otherwise he gets extremely nauseous. Things were under control until the pain management dr. decided to try and give him Methadone last night in pill form, he took three doses and today the stomach problems started all over again. I feel like I am back to square one, with no way out. Sorry fro the rambling. I'm very confused right now.

[john]

CYP3A4 is an enzyme like Fay said that essentially eliminates Iressa from the blood stream. If you search for "Iressa No Nos" on this board.

Grapefruit and other things contain CYP3A4 and may reduce the efficacy of Iressa. Is it possible that your dad was accidentally taking something that would reduce the Iressa's effects?

It is unbelievable that these exclusion criteria are there. The companies should at least offer the drug - they would get a better indication if it worked. Plus I think the half-life of Iressa is pretty short, there shouldnt be any Iressa that left after a few months that would taint the trials' results.

Anyway if you go to the fda web site - there is a way if you fill out the paper work and push VERY hard to get the drugs

http://www.fda.gov/cder/cancer/singleIND.htm

http://www.fda.gov/cder/cancer/access.htm

You have obviously done your research and have been contacting the drug manufacturers. Good luck with getting something

[KC]

Thanks John. Actually, my father doctor was in to see him this morning and did write a prescription for the Xeloda. That is all I know, as I only spoke to my dad on the phone. As far as when he was taking the Iressa, I believe at the time he was also taking a combination of chinese herbs that we received from an herbalist, maybe that had something to do with the Iressa not working. I really wish my father's onc. would let him give it another try. I called Bristol-Meyers Squibb this morning and they said that the physician needs to call them and request an application to receive Erbitux under a compassionate use program for lung cancer. She then went on to say that there are income guidelines and that if my father has too many assets or income that they won't give it to him that way. He is by no means a rich man, but he does receive his pension as he is retired. Who knows. I'm getting really confused as to which way to push. To try the Xeloda or push for the Iressa again. I know my father doesn't eat grapefruit or drink the juice. I have to do that search you spoke about to see what may have interacted with the Iressa.

[KC]

It is unbelievable that these exclusion criteria are there. The companies should at least offer the drug - they would get a better indication if it worked. Plus I think the half-life of Iressa is pretty short, there shouldnt be any Iressa that left after a few months that would taint the trials' results

John,

I think the reason they exclude those who have tried Iressa or drugs that works simililarly from these trials is not because it is still in the bloodstream, but because they figure that if the Iressa didn't work then their drug won't work either, they want "fresh" patients I guess. Also, are these forms only good for drugs that are not FDA approved yet, like Tarceva?? I assume that is correct. I wouldn't fill one of these out for Erbitux, since it is already approved.

[john]

Tarceva is chemically different than Iressa. The same target but different drugs. They target tyrosine kinase on the INSIDE of the cell.

They are both small molecules (I think). They target EGFR downstream from the receptor on the outside of the cell

Erbitux (cetuximab) is a monoclonal antibody and targets the EGFR on the OUTSIDE of the cell. So they all act a little differently.

Ginny and Norme,

Let me explain something. The file that contains the paperwork on the Iressa Trial I was in is located in a box at the back of a closet that has other large heavy boxes on top of it. Today I don't have anyone here to help me reach the box that contains the file, and there is no way I can lift the boxes on top of it by myself.

Here is what I do remember about it:

You have to avoid foods, herbs, and drugs that are inhibitors or inducers of the liver enzyme CYP3A4. Some of the things I remember as being on the list are certain ulcer medications, antifungals, anticoagulants, St. John's Wort, grapefruit .

While I was in the trial I kept notes on CYP3A4 in my purse, so that anytime I received a new prescription I could contact the Pharmacy or many times the drug manufacturer to see if the new drug acted upon this particular liver enzyme. Hope this information is helpful. Will be glad when I regain the muscle strength in my arms and legs and everywhere else. I HATE having to ask others to help me move things around.

I am not really sure about the forms. You could try contacting someone at the FDA, they will hopefully provide guidance

The effectiveness of single-agent vinorelbine was demonstrated in a study by Crawford et al[9] in which 216 patients with stage IV NSCLC were randomized to either vinorelbine at 30 mg/m2 every week or 5-fluorouracil(5-FU) and leucovorin given every 4 weeks.The median survival time for patients who received vinorelbine was 30 weeks with 25% of patients alive at 1 year compared with a median survival time of 22 weeks and 16% of patients alive at 1 year for those treated with 5-FU/leucovorin. Objective response rates were 12% for the vinorelbine arm and 3% for the 5-FU/leucovorin arm. The major toxicity of vinorelbine was granulocytopenia.

What are the doctors suggesting as far as treatment?

From my understanding of BAC, your dad does not have "PURE BAC", since it left the lungs. Also I read, though it is a controversial issue, is that BAC does not respond well to chemo, but your dad did.

The only clinical studies of Xelada are with another chemo.

CPT-11/Xeloda and taxol?/Xeloda. I think the combinations have pretty bad side effects

You might want to research 5-FU and NSCLC and see what the response is, since Xeloda is essentially oral 5-FU.