Monday, 16 November 2015

Lomustine, Carboplatin, Irinotecin... which would you pick?

All -

Dad's oncologist believes that given his decline while on Temodar we should try another option for our next round of chemo in a few weeks.  She said that the choices are Lomustine, Carboplatin, and Irinotecin.  Dad is also taking Avastin (started last week).  Our full cocktail is posted to this blog.

If you had the option to 'pick', which would you push for?  We don't have any genetic testing.  Dad's tumor had a biopsy but no surgical resection.  I've been trying to obtain his MGMT methylation status but it has been nearly impossible to request the test.  Lots of back and forth with nothing.

I'm now beginning to research these three options but want your opinions as well.

Thanks as always..


  1. Hi Annie,
    What were the symptoms of his "decline"?

    In 2015 it's amazing that alkylating agents like TMZ and CCNU/lomustine are still being prescribed without even attempting to test for MGMT status! We've known about this predictive biomarker for over 10 years (longer actually). I'll stop here because I feel a rant coming on. At the very least the patient/caregivers should get full co-operation if this testing is specifically requested!

    Lack of knowledge about MGMT status makes this a more difficult choice. CCNU is an alkylating agent, that alkylates DNA in a location that can be repaired by MGMT. Effects of irinotecan and carboplatin on the other hand are not subject to MGMT-mediated repair. Irinotecan + Avastin has only been marginally more effective than Avastin alone in trials so far. I don't recall seeing any trials testing Avastin + carboplatin. Carboplatin is usually reserved for later recurrences after first-line therapies have failed.

    I would rank them in this order: CCNU, irinotecan, carboplatin. But I would push hard for the MGMT methylation testing before making a final decision. What has been the problem with getting this test done?

  2. Thank you for ranking them for me. I share your 'rant' regarding MGMT. Such BS.

    So it has been up and down, with I'd say 2 significant periods of decline: September 18th (day after surgery was cancelled - pre-treatment) Dad began dry heaving and complaining of headaches. Upped his dex to 8mg twice daily which resolved this in a day. October 30th Dad began nodding his head (sort of shaking it no) and clenching his teeth intermittently. His speech also got worse and his arms were crossing over the front of his body when the Dr. asked him to grab her hands. We were told to engage hospice and given pain meds, but then he got better after another increase in steroid (8mg 3x day) including a one time 10mg IV steroid. Overall his right side is much weaker and he can't bear weight for more than a moment or two (example, getting into a car) which started about 4 weeks into radiation, but his brain appears sharper and his speech is better. I'll forward you my email thread to family which has a bit more detail if you'd like to review it. I am not convinced that it's all tumor burden - I still want to pin it all to radiation necrosis. But that's likely delusion on my part.

    The MGMT status.. where to begin. I requested months ago but was told that the request was set aside as we were planning for surgery and would have a greater sample to work with (also a sample from the same hospital as the NO. biopsy was done elsewhere). Surgery got cancelled, test was not done. Then I was told I needed to pay for it first and to call LabCorp. LabCorp was confused that I was calling them, said the NO had to order it before I can pay. Talking maybe $700. So completely stupid given the cost of everything else... ugh. I was told to have the NS who did the biopsy request it. He called me back personally and said that was wrong - have the NO request it. I requested it again, I think the nurse went to Peru, and nothing happened. I just called again moments ago and sent two emails. I'm also begging the other oncologist we see (not NO) in case she can request it. I don't know what I can do here. It seems urgent to no one.

    1. Also, his short term memory has IMPROVED. Dramatically. About 3-4 weeks into radiation he would forget things within minutes. Now he's back to normal in that regard.

    2. Thanks for all the background info and the email chain. That really puts things into better perspective.

      So it was the local oncologist who wants to try something besides Temodar, not the NO. Let's see what he has to say. And yes, keep pushing for the MGMT testing, good to hear that you're still trying.

      So it sound like much of the improvement has come since he started Avastin, which is often the case. I often suggest chloroquine and DCA as additions to Avastin therapy. I know you already have him on hydroxychloroquine (Plaquenil). This is basically chloroquine with an additional hydroxy group attached to the molecule. Whether that makes any significant difference in efficacy (chloroquine versus hydroxychloroquine) I don't know. DCA would be well worth looking into esp. now that he's on Avastin.

      I know your dad only had a biopsy, so there's probably a minimal amount of tissue to use for testing, but it wouldn't hurt to ask Chamberlain about the possibility of testing for EGFR status also. But MGMT is first priority. Keep us posted.

  3. Turns out the MGMT test was ordered - and the sample was inconclusive: It appears that the attempts to analyze the specimen received were not successful--says this happens about 5% of the time. So that stinks. I went ahead and ordered DCA just now and will add it once it shows up. Stephen - given Dad just had one major decline really while on Temodar, would you stick with Temodar? I will be talking with the NO more on Monday.

  4. The medium dose daily TMZ is given as mainly as a radiosensitizer. The standard dose 5-day schedule hasn't even been given a chance yet for your dad, so I would say it's too early to say that it's not working for him. It's too bad the MGMT test was inconclusive. Will they try again perhaps? This is all the more reason not to rely on chemo alone.

    But given the lack of information on MGMT status, I would go on the assumption that the status is unmethylated, and that the TMZ will need some help to make it more effective. The agents with MGMT-inhibiting potential are drugs your dad is already on or has been on: Keppra, valproic acid, fluoxetine, disulfiram.

    I've already mentioned DCA and neuropathy. Unfortunately that can also be a side-effect of disulfiram. Some people try to get around this by taking breaks with DCA, such as 2 weeks on 1 week off. Another option would be taking higher dose disulfiram (say 500 mg per day) on the week of chemotherapy, and taking a rest in between cycles.