My boyfriend is 26 with Stage IV lung cancer. Non-smoker, ROS1+. He's been in Xalkori since last June but we recently discovered progression in the brain. Unfortunately, it is leptomeningeal carcinomatosis confirmed by lumbar puncture and MRI. We are trying to get the cells tested to see if this is a resistant version of ROS1 or just normal brain progression since Xalkori doesn't pass the BBB.
He just moved here (San Francisco) from Boston, so we have a team in Boston at Dana Farber as well as a team here in SF at UCSF. The teams have been communicating and both suggest an ommaya reservoir with cytarabine injections every two weeks. We are scheduling this as I type. I am also trying to contact our team in Boston so we can start up some compassionate use applications since LMC excludes him from most clinical trials for ROS1.
However, upon reading some literature, posts and Googling (not the best idea, sigh), it seems like many doctors believe that intrathecal chemotherapy isn't really the best option since it just hasn't proven to work that well. Are there any options that are recommended over intrathecal chemo? I know that pulsing Tarceva has shown to work in EGFR+ patients, but this hasn't been tested with Xalkori and ROS1+. I also know that Alimta may also be a better option as well. Thanks again for your time!
Reply # - April 4, 2014, 08:41 PM
Reply To: Leptomeningeal Carcinomatosis in ROS1 patient…what
Hello designeremily,
Welcome to GRACE. I'm so sorry to hear of your boyfriend's LMC diagnosis. I haven't seen any suggestion of attempts to pulse Xalkori, but with regard to intrathecal chemo and pulsed Tarceva Dr. West has said:
"...our current options are largely flailing attempts that have been frustrating and disappointing for leptomeningeal carcinomatosis, and that I really don't recommend intrathecal chemotherapy, because the results just haven't been very favorable, and it's a lot to do for little or no benefit.
I have recently favored the concept of "pulsed" Tarceva given at a dose of 600 mg by mouth one day every four days, which can certainly be beneficial at least for patients with an EGFR mutation... I still tend to try it for patients who don't have an EGFR mutation, but my level of expectation is a lot less, and I'd say that it's the leading treatment option in my mind largely because there isn't any other treatment option that I can generate optimism about." - http://cancergrace.org/forums/index.php?topic=11272.msg92877#msg92877
As far as Alimta, any systemic therapy can help, although to a lesser extent in the central nervous system. There was some talk about high-dose Alimta in the Valerie Harper case which received so much attention last year, but it is certainly not a proven therapy and her case, if it is indeed LMC, may simply represent an unusually indolent form of it.
JimC
Forum moderator
Reply # - April 4, 2014, 09:13 PM
Reply To: Leptomeningeal Carcinomatosis in ROS1 patient…what
Thanks for your reply, Jim.
I need to ask about Alimta again. He had it in 2011 in combo with Carboplatin and experienced progression, so I don't know if that rules it out.
I'm not sure pulsed Tarceva would do much for him either since he is not EGFR+.
I'm just really skeptical about the intrathecal chemo, but I don't see much else we can do right now. I also wish I had full access to this article, as it seems to say that IVC still improves the situation of 35%+ of patients http://journals.lww.com/jto/Citation/2013/05000/Intraventricular_Chemot…
Reply # - April 5, 2014, 09:30 AM
Reply To: Leptomeningeal Carcinomatosis in ROS1 patient…what
Hello designeremily,
If he progressed while on Alimta or shortly thereafter, most oncologists would assume that the drug is not effective against his cancer and would not return to it.
As Dr. West said, he even tends to try pulsed Tarceva in patients without an activating EGFR mutation, just because there really aren't any good options for treating LMC. In general, Tarceva does show a benefit (although reduced) in patients without such mutations, so pulsed Tarceva may be worth a try in the LMC setting.
Dr. Weiss has written a very thorough an informative post on treatment of LMC, in which he discusses the differences in how he treats EGFR mutants vs. non-mutants, and his use of intrathecal chemo: http://cancergrace.org/lung/2011/11/03/pulsed-tarceva-for-lmc/ Be sure to read the comments and his responses; he points out the unfortunate fact that treatment of LMC must be undertaken with eyes wide open, since the chances of substantial benefit are small.
When my wife developed LMC, we tried pulsed Tarceva but despite her activating EGFR mutation, it did not appear to confer any benefit.
I wish we had better answers and my hope is for peace and comfort for both your boyfriend and you.
JimC
Forum moderator
Reply # - April 5, 2014, 11:43 AM
Reply To: Leptomeningeal Carcinomatosis in ROS1 patient…what
designeremily,
I'm sorry to say that the options are just pretty poor. There's reason to be skeptical about intrathecal chemotherapy for leptomeningeal carcinomatosis (LMC). I am not a fan of it, but that doesn't mean I have a better option, at least nothing readily available.
We know that XALKORI (crizotinib) doens't really get into the brain/CNS in any meaningful concentration, but we also know that responses of brain metastases have been seen with second generation ALK inhibitors, which we might extrapolate could also be beneficial for LMC in someone with a ROS-1 positive lung adenocarcinoma. I imagine getting on a trial could be close to impossible, since trial options are very hard to find for ROS-1 positive lung cancer already, and LMC would exclude a patient from just about every trial. However, if there is a way to get it as a compassionate use designation, or once ceritinib (LDK378) becomes commercially available (we anticipate soon), it could be possible to at least try it.
Good luck.
-Dr. West
Reply # - April 5, 2014, 04:05 PM
Reply To: Leptomeningeal Carcinomatosis in ROS1 patient…what
Thank you Dr. West and Jim.
I think our route is to try to get compassionate use for at least ceritinib. I want to try for compassionate use of PF-06463922 but it is in Phase I of trials and what I've heard is that usually CU isn't given out for Phase I.
We're going to get the port put in, get the first injection but go for a consultation with Dr. Shaw to see what her opinion is as well. Thanks so much for your help.
Reply # - April 5, 2014, 09:21 PM
Reply To: Leptomeningeal Carcinomatosis in ROS1 patient…what
designeremily, I just wanted to let you know how sorry I am that your boyfriend has to deal with this condition at such a young age. I hope he can have a sustained and durable response.
Reply # - April 9, 2014, 10:46 PM
Reply To: Leptomeningeal Carcinomatosis in ROS1 patient…what
Hello designeremily
I just read your post from April 4 and want to let you know that I am praying for you and your boyfriend to have a favorable outcome from whatever treatment he chooses for his LMC. My wife, Beth, was EGFR positive and pulse dosed Tarceva and had some limited success but ultimately lost her battle after 5-6 months. You have a special role as his caregiver and he will need all the love and care you can summon in the coming weeks, months and hopefully years. Make the most of every good day he has. There are a number of us who care or cared for LMC loved ones following Grace and we are all pulling for your boyfriend. I know the prognosis stinks but don't give up hope. Miracles do happen. Bob