A website to provide support for people who have or have had any type of cancer, for their caregivers and for their family members.
Results 1 to 4 of 4

Thread: Cisplatin/Mitomycin

  1. #1
    Newbie New User
    Join Date
    Nov 2018
    Posts
    2

    Cisplatin/Mitomycin

    All,

    For the last 18 months, I have been reading your posts, following your stories, and learning SO much; sometimes more than I learn from our doctors. My wife is in her late 40s, and was diagnosed with Stage 4 PC in early 2017. BRCA+, she immediately started Folfirinox and toughed out 16 rounds before her neuropathy became too tough to handle. Because of the good response and the fact that she is BRCA+, she took a break for a few months and she went "off label" for a PARP inhibitor called Olaparib. After the first scan two months later, things looked stable, and the neuropathy was settling down a bit. However two months later, the markers were up, the tumor pain was coming back, and the scan showed the disease progressing. Because the neuropathy was still pretty bad, she went back to Folfirinox without the oxaliplatin, but a few rounds in, the numbers and the pain were shooting higher. Added back in the oxaliplatin for a few rounds, but the scan showed progression. Changed horses to Gem/Abrax but after 8 rounds, the scan showed more growth and more spreading.

    So here we are; we are combing through trials, and while we wait, the doctor would like to have her start Cisplatin/Mitomycin. I have two concerns; 1. The added neuropathy from the Cisplatin. Her feet are awful; every time she stands up, it looks as if she is walking on broken glass. This pain does subside after a while, but then comes back as she sits, or lays down for a period of time. And 2. While we wait for the right trial, what if she gets sicker from the Cis/Mito and then becomes ineligible for certain trials.

    Anyway, she is the strongest person I know, and would love to hear if anyone has had experience with the Cisplatin/Mitomycin and would be willing to share their thoughts.

    Thank you.

  2. #2
    Super Moderator Top User ddessert's Avatar
    Join Date
    Oct 2013
    Posts
    2,306
    Blog Entries
    7
    We're sorry that you had the need to join us.

    I'm glad you were able to find the information about BRCA1/2 and platinum / PARPi treatments. Now that you've gone through the "known" effective treatments, you're about to enter the even more speculative treatment options, those whose efficacy is only "hinted" at, discussed mainly between some doctors and researchers.

    It seems most often the case in BRCA1/2 patients that when platinum resistance happens, resistance to PARPi happens at the same time. Not a guarantee, but often enough that PARPi clinical trials are excluding patients that have shown progression on platinums (carboplatin, cisplatin, oxaliplatin). The reverse (PARPi resistance leading to platinum resistance) has not been tested as much (because PARPi are so new in PanCan), but they suspect is also true.

    Mitomycin C (MMC) is supposed to work in a similar way to platinum chemotherapy - inducing double-strand breaks that cannot be repaired without a working BRCA1/2 gene. Although I have to admit not being as well versed on MMC as platinum or PARPi.

    What those previous two paragraphs means for you is that you should have plan B quickly ready in case this doesn't work. And that you may want to make the change sooner rather than later.

    We've had a couple BRCA/PanCan people here in the same situation as you (platinum stops working, so did PARPi) and I had nothing to tell them. Fortunately, I have a couple of leads now that I learned at the last FORCE's hereditary cancer conference in Oct (last month).

    Check out Dr. Kim Reiss Binder's presentation on hereditary pancreatic cancer. She is at UPenn's Basser Center for BRCA and knows a lot about this. Dr. Reiss Binder's presentation focuses a lot on some clinical trials she's running that use PARPi as a maintenance therapy in people who are still platinum sensitive but are encountering neuropathy. It sounds like your wife has already traveled a lot of this path, but it might be worthwhile contacting Dr. Reiss Binder to see if she has something for you. She may be willing to do some things "just outside" the trial (hint, hint).

    Also check out Dr. Razelle Kurzrock's presentation on immunotherapy. Her slides are about immunotherapy in a variety of cancers and hardly mentions pancreatic as there has been little success there. The one bright spot is in tumors with "high mutational burden" or MSI-H. In pancreatic cancer, the MSI-H condition is present in a paltry 1% of tumors. But there is a light at the end of that tunnel that I will describe in a bit.

    Dr. Reiss Binder's presentation has a slide (#22) about when resistance builds up. I'd heard about the WEE1 inhibitor trial elsewhere (NCI MATCH trial) as a possibility. Her combination of PARPi and immunotherapy was also an interesting tidbit of information. So the leads here are combination treatments of PARPi with either immunotherapy or WEE1, ATR, ATM inhibitors.

    Another relevant point of information in her Q&A session (not in the slides), Dr. Reiss Binder likes OXaliplatin better than Cisplatin because she thinks that Cisplatin causes more neuropathy.

    So, now onto immunotherapy. I found the slide on tumor mutation and immunotherapy (#14) the most interesting. The higher the mutational burden, the more likely that immunotherapy will work. Another piece to this puzzle is that BRCA1/2 mutations mean broken repair mechanisms. That puts them on the high-er side of mutation burden, but not enough to make them classified as MSI-H. This immunotherapy slide hints that we may also be more likely to be helped by immunotherapy treatments.

    In fact, 10 years ago, Dr. Kurzrock said they sat in tumor boards, saw these highly mutated tumors and the consensus was that there was nothing they could do for these patients. Today they see these worst-case tumors and see immunotherapy as a way to give them long-term and lasting remissions. These tumors are poor chemotherapy candidates, but good immunotherapy candidates.

    But that's not the end of this story.

    As we have more and more treatments, our tumors develop new mutations to get around and develop resistance to these treatments. So, in theory we are increasing the tumor's mutational burden. I posed a question to Dr. Kurzrock: "Instead of trying to make the tumor better (patch it up), could we push it further along the path it already wants to go? Can we increase the number of mutations so that immunotherapy will start working?". Answer, Yes, that might be possible.

    So the conclusion to all this back-story is that your wife's tumor may now actually be a better candidate for immunotherapy than chemotherapy. She's been through almost two years of treatments that will have increased the number of mutations inside those tumors. Her BRCA mutation could also have pushed her along this path.

    If you want to try the Cisplatin/MMC treatment with no better options right now, you can use the time to do molecular testing on the tumor. Even if you did this before, it will probably have changed since the previous treatment. Although, if this were me, I'm not sure the result would make much difference. Immunotherapy should have far fewer side effects which seems to be a major factor at this point.

    Sorry for the long-winded post to get down to immunotherapy (in combination with something else), but if you can follow my story above, you'll know why it may work and that all the steps you've taken until now may have set you up for a better outcome.

    Hope!
    BRCA2 3398del5
    Dec 2010 - back/abd pain
    May 2011 - Unresectable stage III, 2.5cm tumor
    Jun-Aug 2011 - Gem/Cis, 9 rounds
    Oct-Nov 2011 - Radiation+Xeloda, 25 days in 5 weeks
    Oct 2011-Sep 2012 - shrinking tumor
    Feb 2012 - National Familial Pancreatic Study
    Aug 2012 - Downgraded to stage IIA, PGP
    Sep 2012 - Whipple, T3N0M0, 0.5cm tumor, 0/16 lymph nodes
    Dec 2012 - Quebec PanCan Study
    Sep 2012-May 2018 - NED
    Mar 2013-present - NCT01088789
    @pancanology

  3. #3
    Newbie New User
    Join Date
    Nov 2018
    Posts
    2
    ddessert,

    THANK YOU SO MUCH!!! I really appreciate it. Wondering if I could PM you offline?

    Best.

  4. #4
    Super Moderator Top User ddessert's Avatar
    Join Date
    Oct 2013
    Posts
    2,306
    Blog Entries
    7
    I PM’d you on this forum,

 

Similar Threads

  1. Xeloda and Mitomycin C
    By anna lipscombe in forum Colon Cancer and Rectal Cancer Forum
    Replies: 3
    Last Post: 04-13-2013, 02:21 AM
  2. Cisplatin chemo 3 days in a row?
    By mbowers049 in forum Lung Cancer Forum
    Replies: 6
    Last Post: 11-18-2008, 08:33 AM
  3. cisplatin + navelbine
    By alottaluv in forum Lung Cancer Forum
    Replies: 2
    Last Post: 11-06-2007, 08:11 PM
  4. What to choose Gemzar/Cytogen or Cisplatin/Etoposide or alt?
    By moutainman in forum Lung Cancer Forum
    Replies: 0
    Last Post: 08-01-2006, 10:42 PM
  5. Chemotherapy - Cisplatin/Vinorelbine
    By redchez200 in forum Lung Cancer Forum
    Replies: 2
    Last Post: 12-23-2005, 03:43 PM

Posting Permissions

  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts
  •