Temodar Resistance

My father was diagnosed with GBM Grade IV in August and has completed his resection and first round of radiation / Temodar. He had a good AGT test and Duke put him on Temodar for 2 more months. I understand that Duke generally likes to rotate chemo treatments because they believe that the Cancer will eventually become resistant to the Temodar if they stay on it too long. But how long is too long? A doctor at NIH has recommended we stay on Temodar for 6 months which goes against Duke's resistance regimen. Does anyone have information on how long someone should stay on Temodar for or anything to back the Duke theory that the body will become resistent?

My husband is being treated at UCLA and they have him on a two year temodar regimen. He is almost to the one year mark and still has no regrowth. We feel that he is obviously having a good response to temodar since he was only given a 6 month prognosis and he has surpassed that. Hope this helps.

Patty

Hi,
My mom was dx 7/05 and has been doing well on Temodar. However, it is not about my mom I am writing to you about. My neighbor also has GBM. (what are the odds) He was dx 8 mos. before my mom. He was recently told Temodar was no longer working for him and that new avenues needed to be explored. I mentioned my mom going to Duke and they jumped at the chance. So I am guessing just over a year after starting treatments, Temodar simply didn't work anymore. They are currently looking into this. I got my mom into a clinical trial at Duke starting in just over a month. As you mentioned, Duke had my mom stay on Temodar for two months. Maybe we'll be in the same trial. As far as "backing" Duke, no one can. They are entering into a trial. We can only hope that this one is the CURE. After speaking to Dr. Friedman at Duke he also said to me that they rotate the drugs.
I hope some of this gives you some answers and dosen't confuse the matter.
Take care,
Dana

I was only on Temodar for a few months before I experienced regrowth. However, I belong to a listserv for brain tumor patients and one member resently started his 44th month of Temodar.

Dana,

That is crazy that both your mother and neighbor have this. What trial did you get your mom into at Duke? What does it entail?

Hi,
It is so weird to have such an awful disease all around you. I watch my neighbors symptoms and hope and pray my mom dosen't suffer the same way.

Duke reqiures you get in touch with them and figure out the type of trial your loved will try. Some people do not qualify for trials. I live in Massachusettes while my mom is in New Jersey so I had to cover all of the grounds via fax,fed ex,phone,etc.
You will need to get films, reports,pre-post MRI's etc. It takes some time to gather so start early.
Good luck,
Dana

My wife is also a Duke patient and is currently on the rotational chemo regimen. She has had surgery (100% resection, IL13 trial for newly-diagnosed, radiation, and is in the middle of her third round of Temodar (200mg/m^2). Temodar has been proven to be the most effective chemo drug available to treat GBM patients - yielding a 2.5 month increase in survival according to a European/Canadian study. However, Temodar is not a cure. Temodar works by interfering with DNA replication when cancer cells divide - targeting 3 separate chemical locations. A certain percentage of cancer cells are able to repair the damage done by Temodar and continue dividing. Eventually, the cells susceptible to Temodar will be killed and the ones resistant will become predominant, leading to tumor recurrence and progression. Hence the logic behind a rotation. The major centers (Duke among them) are ahead of the ballgame in treating patients as individuals rather than a group. Our local Oncologist in Atlanta wanted my wife on "Temodar until Progression", which didn't work for us. Since BCNU and CCNU are chemical cousins of Temodar, you begin to have fewer options once Temodar no longer works (and only 30%-40% of patients respond to Temodar anyway...). My wife fits the profile for Tarceva (EGFRvIII expression, PTEN intact) and that will be the next drug in her rotation. We are looking at combinging Temodar and Tarceva for 12 weeks, then rotating to CPT-11/Avastin (CPT-11 inhibits Topoisomerase I and has a completely different kill mechanism than Temodar, while Avastin is an Angiogenesis inhibitor) for another 12, then finishing our 52 weeks with more Temodar. I don't know if that helps or not. Think of GBM's as an enemy camped out in your father's brain. Once you kill as much as you can with surgery and radiation, you have to block ALL of the roads leading out of the camp to keep the cancer in check. If you block only one, eventually the enemy will find a way out of camp and show up on your flanks. Best of luck with you and your father.

The million dolar question is just how long should someone stay on Temodar before they make a switch. I am in search of active studies that may help in answering this question. Any leads to studies or trials regarding this would be greatly appreciated.

To date there have been no trials to establish the optimum length of time to take Temodar, but 6 months after radiation is becoming standard as the European/Canadian study used a 6-month post-radiation timeframe for their Temodar trial. This trial was established to determine if concurrent Temodar and radiotherapy followed by adjuvant Temodar was more effective than radiation alone, not to establish optimum length of time to take Temodat. There have been trials to determine the longest period of time that someone can take Temodar without unacceptable toxicity. 2 years was established as a good maximum time, but we know people who have taken Temodar longer. Bottom line is everyone's tumor is different and will respond differently to different medications over time. I realize this doesn't answer your question. Duke hasn't published any data on their rotational regimen, and they are the only center to my knowledge that does the rotation before progression. But they do have data available - they were one of the early Temodar trial centers and can discuss their results with you if you request (we have). Good luck.

Very interested in the outcome... of what is decided.. I had posted msg a few months ago about my dad also being diagnosed with GBM.. He has underwent 2 surgeries in the past 6 months and has recently had the Cyber Knife done as well... Currently in the hospital for past 3 weeks w/ serious infection in his leg.. He did have Type 2 diabeties and now because of meds he is taking is a full blown diabetic , therefore making this infection even worse. As soon as they heal this infect . they are ready to start him on the Temodar.........ANyone can check out my 1st msg a few months back if needed..In it I mentioned his Non-Hodgkins Lymphona and the Vietnam war