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How to overcome Tarceva Resistance?


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Hi All,

We just found out that my father has prob become resistant to Tarceva considering there has been growth in his liver tumor in addition to a brain met.

Anyone who has experience/knowledge of this that can offer me some insight?

What treatment alternatives were you offered? The onc. were not too helpful only stating that they maybe increaseing the dose of Tarceva. Even that isn't set in stone yet.



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SHirley welcome to the board first off. Sorry to hear about your Dad adnAm glad you are close by. it has beene my experience that when the body becomes resistant to a drug for chemo the Onc will change the treatment plan and Drug used. I am not sure if increasing the dosage will work or not. What other treatments has your dad been on? there is also a new study out of University of Chicago that has shown the use of Tarceva and Celebrex have had great results and promise also Tarceva avastain combo info here;

ATLANTA (MarketWatch) -- A small study suggested that combining the cancer drugs Avastin and Tarceva could be more effective than chemotherapy in treating people with a form of lung cancer.

Researchers say the study seems to lend support to the relatively new concept of combining so-called targeted therapies, which generally have been prescribed either alone or with chemotherapy. Targeted therapies are designed to focus on cancer cells, while older chemotherapy regimens can also attack healthy cells.

Avastin currently is marketed in the U.S. by Genentech Inc. (DNA), South San Francisco, Calif., as a first-line treatment for metastatic colorectal cancer in combination with chemotherapy. It's marketed outside the U.S. by Roche Holding AG (RHHBY) of Switzerland, which is the majority owner of Genentech. The companies are studying Avastin in numerous other cancer types, and some doctors already prescribe it in other cancers.

Tarceva is approved to treat patients with locally advanced or metastatic non-small-cell lung cancer after failure of at least one prior chemotherapy regimen, and in combination with chemotherapy for the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer. It's co-marketed in the U.S. by Genentech and OSI Pharmaceuticals Inc. (OSIP), Melville, N.Y., and outside the U.S. by Roche.

The new Phase II study involved about 120 patients grouped into three different treatments: Avastin combined with Tarceva, Avastin combined with chemotherapy and chemotherapy alone. The study tracked progression-free survival, which is the time it takes before either new tumor growth or death.

The study found that median progression-free survival was 4.4 months in the Avastin-Tarceva patients; 4.8 months in the Avastin-plus-chemotherapy arm; and three months in those getting chemotherapy alone, according to a press release from Genentech and OSI Pharmaceuticals. The data also suggested the Avastin-chemotherapy arm reduced the risk of cancer progression or death by 34% compared to chemotherapy alone, and the Avastin-plus-Tarceva reduced the risk of cancer progression or death by 28% compared to chemotherapy.

The combination therapy of Avastin plus Tarceva resulted in fewer serious adverse events compared to either chemotherapy-containing arm, the companies said. The rate of fatal pulmonary hemorrhage was consistent with previous Avastin trials in non-small-cell lung cancer.

The results were presented Monday at the annual meeting of the American Society of Clinical Oncology, a gathering of cancer specialists in Atlanta.

The companies cautioned that the new data doesn't provide definitive conclusions or reach statistical significance in the differences among the three treatment arms, citing "the planned exploratory nature and small sample size of the study."

A Phase III trial of the Avastin-Tarceva combination in relapsed and first-line non-small-cell lung cancer patients is underway.

"If the trends continued in a well-powered trial, it would be a nice result," said Louis Fehrenbacher, an oncologist with Kaiser Permanente in Vallejo, Calif., who presented the data here Monday.

-Contact: 201-938-5400

Tarceva Celebrex study info is here below;Celecoxib May Increase Benefit of Erlotinib for Lung Cancer

NEW YORK JUN 01, 2006 (Reuters Health) - The addition of celecoxib (Celebrex) to treatment with erlotinib (Tarceva) for advanced non-small cell lung cancer (NSCLC) appears to be safe, and to increase the proportion of patients who respond to erlotinib, results of a phase I trial suggest.

Previous research has demonstrated that the cyclooxygenase 2 (COX-2) and epidermal growth factor receptor tyrosine kinase (EGFR-TK) are overexpressed in some cancers, including NSCLC. Erlotinib is a highly specific EGFR-TK inhibitor, and celecoxib is a COX-2 inhibitor, Dr. Karen L. Reckamp and her colleagues note in their report, published in the June 1st issue of Clinical Cancer Research.

Only about 10% of patients with NSCLC respond to erlotinib, the researchers point out, and COX-2 expression promotes resistance to erlotinib. The investigators theorized that inhibiting both pathways would inhibit tumor angiogenesis, invasion, and growth.

To investigate these interactions, Dr. Reckamp, from the David Geffen School of Medicine at UCLA in Los Angeles, and her associates conducted a dose-escalation trial involving 21 patients with stage IIIB or IV NSCLC.

The patients took oral erlotinib 150 mg for two 4-week cycles. Then, in groups of three, patients were consecutively treated with doses of celecoxib escalating from 200 mg twice daily to 800 mg twice daily. Dose escalation was considered when all three subjects in a given group did not experience any dose-limiting toxicity after 28 days of treatment.

The optimal biological dose (OBD) was defined as the lowest dose level showing optimal biological activity -- maximal decrease in urinary levels of PGE-M (the major urinary metabolite of prostaglandin E2) with no dose-limiting toxicity.

Patients were treated until their disease progressed or unacceptable toxicity occurred. After 12 months, the celecoxib was stopped, but treatment with erlotinib was continued. The combination did not cause any additional toxicity, the investigators report, of which the most common were rash and diarrhea. The OBD was 600 mg twice daily.

Dr. Reckamp's team observed that seven patients experienced partial response and five maintained stable disease (disease control rate of 57%). According to a UCLA press release, the longest duration of response so far is 93 weeks, which Dr. Reckamp said is about three to four times longer than the average duration of response for patients with advanced NSCLC.

At the time of analysis, the authors note, eight patients had died secondary to progressive disease.

Based on these findings, the investigators are planning a phase II trial of celecoxib 600 mg twice daily plus erlotinib versus erlotinib plus placebo for treatment of advanced NSCLC.


Clin Cancer Res 2006;12.


These are the 2 newest research studies done using Tarceva in combo with other drugs. There are other treatments separately of course by switching Treatments of course. Remember Knowledgge is power and any info to ask Onc about is better than none. Will try to copy your original post into General Forum For more responsiveness on personal experiences. Keep me posted on what is going on and let me know if I can do anything. Sorry so long but may help some I think.

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Hi Randy,

Thank you so much for getting back to me. I had called the onc fellow last week in regards to adding the Celebrex to the Tarceva. She told me that she has heard of it but since it's only in phase 1 clinical trial so it will not be an option for him.

I have posted this question on a different forum and a gentleman had told me that if the doctors do not want to prescribe Celebrex then Naxoprene (sp) could be used as a substitute. The common name for Naxoprene is Aleve. This gentleman suggested that I let the doctors know that we are willing to use Aleve instead of Celebrex and see what they say. He thinks that since it's not an approved treatment for lung cancer, the doctors are afraid of malpractice.

I'm just afraid that even if my father got the Celebrex it wouldn't help since we're pretty sure he's resistance to the Tarceva already.

Any success stories of anyone that has overcome Tarceva would be excellent.



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There is a new class of drugs called irreversible EGFR inhibitors.

The theory is that they will work when the cancer mutates and becomes resistent to Tarceva

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

HKI-272 is one of the drugs. There are a few others in early trials. They are very new and Phase I/Phase II trials, but it may be an option

http://www.clinicaltrials.gov/ct/show/N ... 3B?order=6

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