Dear Dr. West,
My mother was an 85 yo Asian, non-smoker, who had NSCLC and was positive for EGFR and c-met mutations. She did well on Tarceva for 2 years then showed progression. In waiting for a clinical trial to begin, she did 6 cycles of Alimta then 2 or 3 cycles of Sutent. When she had her MRI as part of the screening process for clinical trial, she showed too numerous to count brain metastases. She was asymptomatic. We were told that WBR was her only choice and that it would extend her life. We did what was recommended and at her next scan, the brain metastases was gone but she was shown to have leptomeningeal involvement. That's when I found your discussion and the article about pulsitile dosing of Tarceva on this site and her oncologist agreed to try it for the leptomeningeal disease. Her next two MRI's were negative. The leptomeningeal disease was gone! The whole family feels that the WBR was the worse choice that we could have made for Mom. We know that Tarceva is a small molecule, TKI and that it can pass through the blood-brain barrier. My question is; For people who are EGFR positive, would rechallenging with Tarceva (with or without pulsitile dosing) have worked just as effectively on brain metastases as WBR? Are there any articles you could refer to? Thank you. This answer may help someone else.
Sun, 06/23/2013 - 13:38
It seems like it is fair to say she has had a good response to her treatments. It sounds like it is difficult to say whether the effect seen can be attributed to the Tarceva, the radiation, or both.
Leptomeningeal cancer can be difficult to assess even on MRI, since it is like a sugar-coating around the brain rather than a discrete mass. And the effects of radiation unfold over months, so it could cause MRI changes that may mimic leptomeningeal disease, or could cause shrinkage over a period of months. So it seems difficult to know exactly which to credit for the response seen.
The fact is, this field has a lot of uncertainty, and we don't know whether pulsatile dosing is better than WBR. To my knowledge there haven't been any trials specifically comparing pulsatile dosing to WBR in lung cancer. Most guidelines would side with WBR since there is a larger body of evidence to support WBR in this setting. However, pulsatile tarceva would be attractive to try first for EGFR mutant patients, especially in someone who is not having symptoms.
Overall, I'd be pleased with how the lung cancer has done so far, and I wish all the best for her future.
Sun, 06/23/2013 - 20:07
The pulsed Tarceva (erlotinib) approach is not well studied anyway, but it's far better studied for leptomeningeal carcinomatosis than for brain metastases. I would absolutely favor WBR as the treatment of choice for multiple brain metastases, especially in someone who developed those metastases while on daily Tarceva. We have extremely little information on the incremental efficacy of pulsed Tarceva in someone who was already on the standard regimen of daily Tarceva and then developed disease progression in the CNS.
Mon, 06/24/2013 - 06:28
Thank you for your replies. To Dr. West- My mother had been off Tarceva for about a year because she progressed. She did the Alimta and then the Sunitinib for therapy as she was waiting to get into a clinical trial. It was during this time ( when she was off Tarceva) that I believe she developed the brain metastases. I found out about the pulsitile dosing only after she had the WBRT and developed leptomeningeal disease. I firmly believe(because she was EGFR positive) that if we had rechallenged her on Tarceva instead of doing WBR, it would have taken care of the brain metastases. It may have been a better way to treat an 85 year old woman. WBRT left her severly debilitated. It's barbaric. Her quality of life suffered. She passed away September 2012. Thank you for your time.:)
Mon, 06/24/2013 - 19:20
I'm truly sorry.
Tue, 06/25/2013 - 02:09
My wife has been on pulsed doses of Tarceva for LMC since mid May 2013. She has stage 4 adinocarcinoma/EGFR with mets to liver, bones and brain. Since starting pulsed doses we have had mixed results but the trend has generally been downward. Headaches are not as bad but eyesight has not improved. Weakness in legs continues to get worse. Consistent pain in upper legs and now into knees and back. Gait is unsteady and today she complained of balance issues on left side. Periodic incontinence and constant constipation. Extreme fatigue at times and general confusion often worse in evening or when tired.
Her dosing is on Thursdays. Her best days of the week are generally on Saturday, Sunday, and Monday. She gets IV's on Thursdays with her pulsed dose and just started regular IV's on Mondays too. The IV's tend to perk her up.
She requires regular monitoring and now needs help dressing. The neurological symptoms scare both of us and as I said in a previous post I feel like we are running out of options and time.
Sorry to run on like this but this condition is horrible and part of the reason I'm up late tonight searching for clues on what to do. If this helps anyone at all understand this disease better then perhaps what I have described is beneficial. Now maybe I can go back to bed.
Tue, 06/25/2013 - 03:12
Bob, thank you for sharing. This info is definitely helpful towards better understanding and, possibly, better dealing with the disease. You are in my thought.